Test de Efort

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Vol. 24, No. 4, 2014
ORIGINAL ARTICLES
Acute type A aortic dissection. A single center experience

O. Stiru, L.F. Dorobantu, A. Pasare, S. Bubenek, D. Filipescu, H. Moldovan, V. A. Iliescu
251
Predictive value of exercise stress testing in a tertiary cardiological center 260

D. Gherasim, M. Jalb, M. Lupu, D. Deleanu, C. Ginghin, E. Apetrei
REVIEWS
Dillemas in the use of therapeutic hypothermia after cardiac arrest
268
Cardiac dysfunction of antineoplastic agents in breast cancer patients
271
Utility and prognostic value of exercise stress testing in post

revascularization patients
278
Behcet disease: one of the etiologies of myocardial infarction in young

patients
286
D. Zahger
A. M. Popar-Voica, A. Clin, B. A. Popescu, A. M. Mitric, R. Anghel, R. Jurcu, C. Ginghin
D. Gherasim, B. Moise, E. Apetrei
CASE PRESENTATION
B. Hanane, N. Malika, H. Rachida
Unexplained left ventricular hypertrophy, arrhythmias and conduction

disorders: take into account Anderson-Fabry Disease (AFD).
A case report of a diagnosed and under treatment AFD in a heterozygous
female, with severe left ventricular hypertrophy and conduction
disorders
289
C. Vcrescu, D. Lighezan, M. Mangea, E. Goan, T. Ruhmann, D. Cozma
What could hide an oncologic patient with exertional dyspnea?
294
Complication of a diagnostic peripheral arteriography
297
European Guidelines on cardiovascular disease prevention in clinical

practice (version 2012)
299
AGENDA
National and international cardiology agenda 2015
391
INSTRUCTIONS FOR
AUTHORS
Instructions for authors
395
IMAGES IN CARDIOLOGY
R. Silite, M. Jidveian, R. Ianula, D. Sptaru
L. Predescu, M. Postu, P. Platon, M. Rugina, M. Gavanescu, M. Croitoru, A. Bucsa, L. Zarma, D. Deleanu
GUIDE
Vol. 24, No. 4, 2014
Vol. XXII, Nr. 1, 2007
ARTICOLE ORIGINALE
Disecia acut de aort de tip A. Experiena unui singur centru
251
Valoarea predictiv a testului ECG de efort ntr-un centru teriar

de cardiologie
260
Dileme n utilizarea hipotermiei terapeutice dup stopul cardiac
268
Disfuncia cardiac indus de agenii antitumorali la pacientele cu

neoplasm mamar
271
Utilitatea i valoarea prognostic a testului de efort post

revascularizare
278
O. Stiru, L.F. Dorobantu, A. Pasare, S. Bubenek, D. Filipescu, H. Moldovan, V. A. Iliescu
D. Gherasim, M. Jalb, M. Lupu, D. Deleanu, C. Ginghin, E. Apetrei
REFERATE GENERALE
D. Zahger
A. M. Popar-Voica, A. Clin, B. A. Popescu, A. M. Mitric, R. Anghel, R. Jurcu, C. Ginghin
D. Gherasim, B. Moise, E. Apetrei
PREZENTARE DE CAZ
Boala Behcet: una dintre cauzele infarctului miocardic la pacienii tineri 286
B. Hanane, N. Malika, H. Rachida
Hipertrofie ventricular stng de cauz neexplicat asociat tulburrilor

de ritm sau de conducere: suspiciune de boal Fabry-Anderson.
O prezentare de caz a unei paciente heterozigot diagnosticate i n
tratament pentru boala Fabry-Anderson, cu hipertrofie stng sever i
tulburri de conducere
289
C. Vcrescu, D. Lighezan, M. Mangea, E. Goan, T. Ruhmann, D. Cozma
IMAGINI N CARDIOLOGIE
Ce poate ascunde un pacient oncologic cu dispnee de efort?
294
Complicaie a unei arteriografii periferice diagnostice
297
Ghidul Societii Europene de Cardiologie pentru prevenia bolilor

cardiovasculare in practica clinic (versiunea 2012)
299
R. Silite, M. Jidveian, R. Ianula, D. Sptaru
L. Predescu, M. Postu, P. Platon, M. Rugina, M. Gavanescu, M. Croitoru, A. Bucsa, L. Zarma, D. Deleanu
GHID
AGENDA
Calendarul manifestrilor tiinifice cardiologice 2015

Manifestri tiinifice i cursurile Societii Romne de Cardiologie 2015
Manifestri tiinifice internaionale 2015
391
INSTRUCIUNI PENTRU
AUTORI
Instruciuni pentru autori
395
Romanian Journal of Cardiology | Vol. 24, No. 4, 2014
ORIGINAL ARTICLES

Ovidiu Stiru1, Lucian F. Dorobanu1, Alexandra Pasare1, erban Bubenek1, Daniela Filipescu1, Horaiu Moldovan1,
Vlad. A. Iliescu1
Abstract:
Objective Acute aortic dissection (AAD) is the most frequent and catastrophic manifestation of the so-called
acute aortic syndrome (along with intramural hematoma, penetrating aortic ulcer, and ruptured thoracic aortic aneurysm)3.
The objective of this study was evaluating the cases of acute type A aortic dissection treated in Prof. Dr. C.C. Iliescu Emergency Institute for Cardiovascular Diseases over the last nine years, creating a more comprehensive image of this pathology.
Material and method 290 patients (174 male, 116 female, mean age: 55.8812.13 years) were admitted for acute type A
aortic dissection (ATAAD) in our Institute between January 2005 and May 2013, in all cases transesophageal echocardiography being performed for diagnostic confirmation. The main demographic, clinical and perioperative characteristics of these
patients were followed and the identification of several factors capable of increasing morbidity and mortality rates associated
with acute type A aortic dissection was attempted. Results The distribution of cases was uniform over time, with a slight
decrease of 30-day mortality (p=0.985) and intraoperative mortality rates (p=0.119). Mean age was 55.8812.13 years and
men were more often affected than women (3:2 gender rate). Ascending aorta replacement was the operation performed with
the highest frequency (29.71%) and the lowest mortality rate (16.05%) while the highest one associated with ascending, arch
and descending aorta replacement (83.3%). 29.10% patients were extubated in the first postoperative day. The most frequent
complications were: acute renal failure (61.62%), low ejection fraction 30% (57.20%), multiple system organ failure (MSOF)
(39.48%), neurologic dysfunction (23.62%). Prolonged cardiopulmonary bypass (CPB) time (over 400 minutes, p=0.001) as
well as replacement of the descending aorta (p=0.023) or the aortic arch (p=0.009) associated mortality rates of 80% and 50%,
respectively. Conclusion Type A acute aortic dissection is a frequent pathology in the cardiovascular surgical area. Moreover, it can prove to be a surgical challenge, with increased morbidity and mortality, but in experienced centers the results are
more than satisfying. In our experience prolonged CPB time (over 400 minutes) as well as aortic arch and descending aorta
replacement significantly increased the.
Keywords: type A acute aortic dissection, surgical treatment, mortality rate.
Rezumat: Obiectiv Disecia acut aortic reprezint cea mai frecvent i catastrofic entitate a aa-numitului sindrom aortic
acut (alturi de hematomul intramural, ulceraia aortic penetrant i anevrismul toracic rupt). Obiectivul acestui studiu a
fost evaluarea cazurilor de disecie acut aortic de tip A tratate n cadrul Institutului de Urgen pentru Boli Cardiovasculare
Prof. Dr. C.C. Iliescu n cursul ultimilor nou ani, conturnd o imagine mai clar a acestei patologii. Material i metod
290 pacieni (174 brbai, 116 femei, vrsta medie: 55,88 12,13 ani) au fost internai cu suspiciunea de disecie acut aortic
de tip A n cadrul Institutului n perioada ianuarie 2005 mai 2013, ecocardiografia transesofagian (ETE) fiind efectuat
pentru confirmarea diagnosticului n toate cazurile. Principalele caracteristici demografice, clinice i perioperatorii ale acestor
pacieni au fost urmrite, realizndu-se un studiu descriptiv, cruia i s-a adugat o component analitic prin identificarea
principalilor factori responsabili pentru creterea ratelor morbiditii i mortalitii asociate. Rezultate Distribuia cazurilor a fost uniform de-a lungul timpului, cu o uoar scdere a ratelor mortalitii (p=0.985) i mortalitii intraoperatorii
(p=0,119). Vrsta medie a lotului a fost de 55,8812,13 ani, brbaii fiind mai des afectai dect femeile, cu un raport pe sexe
de 3:2. nlocuirea de aort ascendent a fost intervenia cea mai frecvent (29,71%), care a asociat i cea mai mic rat a mortalitii (16.05%), n timp ce la polul opus s-a situat nlocuirea de aort ascendent, cros aortic i aort descendent, cu o
mortalitate asociat de 83,3%. 29,10% dintre pacieni au fost detubai n prima zi postoperator. Cele mai frecvente complicaii
au fost, n ordine descresctoare: disfuncia cardiac (57,20%), insuficiena renal acut (IRA) (61,62%), difuncia sistemic
multipl de organ (DSMO) (39,48%), disfuncia neurologic (23,62%). Durata prelungit a bypass-ului cardiopulmonar (peste
400 minute, p=0,001) alturi de nlocuirea aortei descendente (p=0,023) sau a crosei aortice (p=0,009) au asociat mortaliti
de 80%, respectiv 50%. Concluzii Disecia acut aortic de tip A reprezint o patologie frecvent n sfera chirurgical cardiovascular. Dei frecvent se dovedete a fi o provocare chirurgical, cu rate crescute de morbiditate i mortalitate, n centrele
Emergency Institute for Cadiovascular Diseases Prof. Dr. C. C. Iliescu

Bucharest, Romania
Contact address:
Ovidiu Stiru, MD
Emergency Institute for Cadiovascular Diseases Prof. Dr. C. C. Iliescu
Sos. Fundeni 258, sector 2, 022328 Bucharest, Romania Phone/Fax:
+40213175227
E-mail: ovidiu_stiru@yahoo.com
Ovidiu Stiru et al.

Romanian Journal of Cardiology

Vol. 24, No. 4, 2014
experimentate rezultatele tratamentului sunt mai mult dect satisfctoare. n experiena noastr, durata crescut a bypassului cardiopulmonar (peste 400 minute) i nlocuirea de aort descendent sau cros s-au asociat semnificativ statistic cu
creterea mortalitii.
Cuvinte cheie: disecia acut aortic de tip A, tratament chirurgical, mortalitate.
BACKGROUND
Acute aortic syndrome (AAS) is a collective term for
several life-threatening acute aortic conditions1 with
similar presentations2: aortic dissection, intramural
haematoma (IMH), penetrating atherosclerotic ulcer
and traumatic transection1, of which acute aortic dissection is the most frequent and catastrophic manifestation, with a reported incidence of no less than 30 cases per million individuals per year3. In its natural evolution ATAAD associates a mortality rate of about 1%
per hour initially, 50% by the end of the third day and
almost 80% by the end of the second week. Much lower,
although still significant are the mortality rates associated with acute type B aortic dissection (ATBAD):
10% at 30 days, reaching values higher than 70% in
the highest-risk groups3. Diagnostic delay is frequent,
increased by a wide spectrum of presentations that do
not evoke clinical suspicion, and adversely affects outcome2. In these cases the gold standard investigation
is transesophageal echocardiography (TEE), ideally
performed with the cardiac surgical team standing by1.
After diagnosis establishment, decisions regarding the
initial management, transfer, indication and timing of
surgery, and intervention for malperfusion complications are mandatory. The surgical treatment of ATAAD
has not been yet subjected to any randomized trials,
but novel therapies particularly with regard to extent of surgeryare being devised and implemented,
especially in the treatment of ATBAD2, which is rather
different. It has been proven that in the absence of complications optimal medical therapy of ATBAD is reportedly yielding an impressively low 30-day mortality rate
of 10% or less. On the other hand, patients presenting
with complicated type B dissection are at substantial
risk of death or major sequelae; in their case a surgical or endovascular intervention must be considered3.
Overall, except in highly specialized centers, surgical
outcomes might be static, and there is abundant room
for improvement2.
MATERIAL AND METHODS

Patients
Prof. Dr. C.C. Iliescu Emergency Institute for Cardiovascular Diseases database was queried to identify all
patients who underwent surgery for aortic dissection
repair between January 2005 and May 2013. A total of

290 patients who underwent repair for acute type A
aortic dissections during this period of time were identified (116 female, 174 male, mean age 55.88 years).
Patients who did not undergo surgery were excluded
from the study. In all cases TEE was performed for
diagnosis confirmation in ICU department or on the
operating table. All demographic and procedural data
and perioperative features of the patients were collected and introduced in an Excel database. 31 variables
were defined, SPSS v 16.0 and univariate analysis were
used for statistical analysis and a transverse retrospective study was created.
Definitions
Acute type A aortic dissection was defined as any surgically confirmed dissection process that involved
the ascending aorta, presenting within 2 weeks from
symptoms onset. Cerebrovascular accident was defined
as any central neurological deficit persisting for more
than 24 h, with CT or MRI confirmation. Chronic renal
insufficiency was defined according to estimated glomerular filtration rate. Diabetes was defined as a history of diabetes mellitus, regardless of the duration or
treatment of the disease. Acute renal failure was defined as one or both of the following: either a sudden increase in the serum creatinine levels over 2.0 mg/dl or
a new requirement for dialysis, postoperatively. Operative mortality included all deaths occurring in the
admission period during which the operation had been
performed, regardless of its duration, as well as those
occurring after hospital discharge, but within 30 days
of the procedure.
Operative technique
The acces was performed through a standard median
sternotomy. Total cardiopulmonary bypass (CBP) was
established in most cases by arterial cannulation of the
femoral or right axillary artery and venous cannulation
of the right atrium. Myocardial protection was ensured through antegrade or retrograde cold blood cardioplegia administration. A vent was placed in the left
ventricle via the right superior pulmonary vein. After
a transverse aortotomy, the ascending aorta and the
aortic valve were inspected and the segment including
the proximal entry tear was resected, followed by repair or replacement of the aortic valve, when needed
Ovidiu Stiru et al.


Vol. 24, No. 4, 2014
and replacement of the ascending aorta. After reaching

a mean temperature of 25-28C, the aortic clamp was
removed and the aortic arch examined and replaced
whenever an arch tear would be identified. The distal
anastomosis with prosthetic collagen impregnated low
porosity graft was then completed under circulatory arrest with antegrade selective cerebral perfusion. Biological glue and Teflon strips were used in all patients for
reinforcement of both proximal and distal suture lines.
RESULTS
290 patients were operated in Prof. Dr. C. C. Iliescu
Emergency Institute for Cardiovascular Diseases between January 2005 and May 2013, the cases being
homogenously distributed throughout the years. Preoperative patient characteristics are summarized in Table 1. The mean age of the lot was 55.88 12.13 years
(minimum 20, maximum 96 years), with a slight male
predominance (1.5 - gender rate) which became greater for the first two age groups (out of three of 20 years
interval defined): 3 in patients under 40 years of age
and 1.84 in those between 40 and 60 years old, respectively. Among associated comorbidities, primary arterial
hypertension prevailed (75%). In all cases transesophageal ecocardiography was performed for diagnostic
confirmation in the ICU department or in the operating room (OR).
The most used site for arterial cannulation, with a
decreasing frequency over time, was the right axillary
Table 1. Preoperative patient characteristics
Characteristic
Age
Mean (55.88 years)
20-40 years
41-60 years
61-80 years
Gender
Associated comorbidities
Arterial hypertension
Bicuspid aortic valve
Marfan Syndrome
Diabetes mellitus
Annuloarctic ectasia
History of myocardial infarction
Previous surgery on the thoracic aorta
Imagistic investigations
Transesophageal echocardiography
Contrast CT
Coronary angiography
Aortography
MRI
Frequency
Male
Female
75%
65%
48.60%
60%
25%
35%
51.40%
40%
90.40%
8.90%
8.10%
5.80%
2.60%
2.10%
2.10%
100%
53.90%
3.10%
2.60%
1.05%
Figure 1. Femoral artery cannulation trend over time.
artery (65.95%), immediately followed by right or left

femoral artery (22.94%) (Figures 1, 2). In all cases the
entry point was removed, thus performing the replacement of one or more aortic segments involved: an
isolated aortic replacement was most often necessary
(29.71%), accompanied by hemiarch (34.8%), arch
(13.8%) and descending aorta replacement (4.8%). The
aortic root was involved in 37.6% cases, repaired in almost three quarters of them through sinotubular junction recalibration, comissures resuspension, David or
Yacoub techniques and in one quarter replaced, either
isolated or as part of a Bentall operation. Operative patient features are summarized in Tables 2 and 3. Circulatory arrest with moderate or deep hypothermia was
Table 2. Operative patient characteristics
Variable
Arterial cannulation site
Right axillary artery
Femoral artery
Left axillary artery
Ascending aorta
Right subclavian artery
Right axillary artery, femoral artery
Aortic arch
Ascending aorta, femoral artery
Aortic valve procedure
Sinotubular junction recalibration
Bentall
Comissure resuspension
Yacoub
David
Replacement
Frequency (%)
65.95%
22.94%
2.87%
2.51%
1.79%
1.79%
0.72%
0.36%
45%
29%
17%
5%
2%
2%
Ovidiu Stiru et al.


Vol. 24, No. 4, 2014
Table 4. Postoperative characteristics
Variable
Figure 2. Axillary artery cannulation trend time.
performed in all cases for tear inspection of the aortic

arch. The average CPB time was significantly longer in
operations involving the aortic arch and the descending aorta (452 min) compared to those with isolated
replacement of the ascending aorta (172 min). Selective
antegrade cerebral perfusion was used in all cases of
arch or hemiarch replacement.
Postoperative characteristics are depicted in Table
4. The average patient was intubated for 23.65 hours
and spent 13.6 days in the ICU ward. 29.10% patients were extubated in the first postoperative day. The
most frequent complications were: acute renal failure (61.62%), ejection fraction 40% (57.20%), MSOF
(39.48%), neurologic dysfunction (23.62%). Surgical
reexploration was necessary in 26.57% cases, the most
common cause being postoperative bleeding. The overall mortality rate was 31.37% (91 patients), with no
Time
Mean ventilatory support period

Mean length of ICU stay
Complications
Ejection fraction 40%
Acute renal failure
MSOF
Hemodialysis
Sepsis
Cerebral stroke
Cardiac tamponade
Acute myocardial infarction
Peripheral ischaemia
Visceral ischaemia
Mediastinitis
Reinterventions
Bleeding
Deep wound infection
Myocardial ischaemia
Tamponade
Peripheral ischaemia
Mortality rate
23.65 hours
13.6 days
Frequency (%)
57.20%
61.62%
39.48%
36.16%
31%
23.62%
26.57%
9.96%
6.27%
3.69%
3.32%
36%
5%
2%
2%
3%
31.37%
significant differences in time, while a marked decrease of intraoperative deaths in the last years, although
not statistically significant, is visible in the chart below
(2005 9.09%; 2013 1.92%, p=0.119). Greatest mortality rates associated with ascending, arch, descending
aorta replacement (83.3%) and with replacement of
descending aorta (60%). Related to the replaced aortic
segment, mortality rates significantly grew at univariate analysis in descending aorta (p=0.023, OR=3.325,
95%CI: 1.118-9.891) and arch replacement (p=0.009,
OR=2.422, 95% CI: 1.227-4.781). Also, while CPB times under 400 minutes associated an overall mortality
rate of 24.57%, over this value the mortality rate tripled:
82.46% (p=0.001, OR=15.127, 95% CI: 1.789-127.899).
Table 3. Operative patient characteristics

Operations performed
Ascending aorta
Ascending aorta and hemiarch
Aortic root and ascending aorta
Aortic root, ascending aorta and
hemiarch
Ascending aorta and arch
Aortic root, ascending aorta and arch
Descending aorta
Ascending aorta, arch, descending
aorta
Root, ascending aorta, arch, descending aorta
Frequency (%)
Mortality rate (%)
Cerebral perfusion
(%)
CPB time (min)
Cross-clamp time
(min)
29.71%
23.55%
22.46%
11.96%
16.05%
27.27%
25.4%
39.39%
6.61%
38%
4.13%
21.50%
172
258
241
294
99
125
167
175
6.88%
5.07%
0.12%
0.20%
45%
33.33%
60%
83.3%
12.40%
9%
3%
5%
350
398
285
452
198
273
103
283
0.04%
0%
1%
351
284

Vol. 24, No. 4, 2014
Figure 3. Mortality rates over time.
DISCUSSION
Acute aortic syndromes (AAS) constitute a spectrum of
conditions characterized by disruptions in the integrity
of the aortic wall, with potentially catastrophic consequences, including classic aortic dissection, intramural hematoma and penetrating aortic ulcer4, although
recent evidences suggest that IMH may in fact be the
classic aortic dissection with small intimal tears that are
not evident with current aortic imaging techniques5. Of
these, acute aortic dissection is the most frequent and
catastrophic manifestation1. Traditional classification
systems, such as the Stanford and DeBakey, facilitate
the decision-making process4; more recently though,
a classification based on the pathophysiological features of the aortic lesion rather than its location has been
proposed; currently it is recommended that AAD be
classified according to both lesion type and location.
Still, while the primary goal of surgery is to obliterate
the intimal tear in the ascending aorta, thereby preventing flow and encouraging thrombosis of the false
lume1, neither of these classification systems dictates
the site of the originating entry tear2.
Diagnosis of ATAAD
The estimated total incidence of AAD (type A and B)
reaches 30 to 43 cases per million of population per
year and apparently continues to increase. ATAAD
constitutes more than half of these, while DeBakey
type I lesions predominate. It is not known whether
the apparent increase in incidence represents improved
rates of diagnosis or the dramatic consequence of an
aging population2.
While immediate decisions with regard to initial
management, transfer, appropriateness of surgery, timing of operation and intervention for malperfusion
complications are mandatory, the diverse presentations
of ATAAD can delay the diagnosis, adversely affecting outcomes2,6,7. Approximately 75% of patients with
Ovidiu Stiru et al.

acute dissection have their initial diagnosis made in a

nonspecialised hospital. In ATAAD, the period of time
between presentation and definitive management reaches ~12 h in the majority of patients, but has been reported as long as ~24 h in 20% to 50% of cases in some
series8. Symptoms, signs, electrocardiograms and chest
X-rays lack sensitivity and specificity, therefore the
diagnosis may be overlooked in 40% of cases, sometimes being established only at autopsy8. The primary
presentation of AAD to the emergency room (ER) is
most commonly an elderly male, with hypertension
and sudden onset chest pain8, as it was in our study. On
hospital admission, 50% of patients are hemodynamically unstable, ~25% have a neurological deficit, over
20% have cardiac tamponade and 6% have already undergone cardiopulmonary resuscitation9. It has been
reported that malperfusion syndromes may be associated in as many as 20-30% of patients presenting with
type A dissection; although often under-recognized at
that time, they remain responsible for significantly increased mortality rates10.
Without clinical suspicion, patients are not immediately channeled into an appropriate imaging pathway2.
Acute aortic syndromes have no reliable point-of-care biomarkers2,8. D-dimer measurements might be for
now the most useful tool: a negative assay is highly predictive that a patient does not have dissection, whereas
a high level makes the differential diagnosis of ATAAD
or pulmonary embolism far more likely and once suspected, definitive imaging comprising CT, transthoracic echocardiography (TTE), transesophageal echocardiography and MRI, is required for confirmation2.
TTE is a rapid and readily available investigation in
the emergency department and it should be performed
without delay in patients with suspected AAS. Owing
to an inadequate window for imaging the ascending
aorta9, TTE has a reported sensitivity of 59-83% in
ATAAD and a much lower one in descending aortic
dissection, but a specificity of 63-93% for the diagnosis
of aortic dissection1. The sensitivities of MRI, TEE and
CT in detecting acute aortic dissection are similar at
approximately 95%9. In a comprehensive meta-analysis
of all three modalities, the most recent studies reported
100% sensitivity and 100% specificity for TEE, helical
CT and MRI, whereas conventional CT (probably the
most widely used technique) was less accurate (sensitivity 83-94%, specificity 87-100%). The intimal tear is
usually located in the proximal ascending aorta or just
distal to the left subclavian artery, measuring less than
5 mm in length - TEE identifies it in about 78-100%
Ovidiu Stiru et al.

of the cases. In another 10-20% of cases, the intimal

flap propagates retrogradely, involving the origin of
one or both of the coronary arteries1. In this situation,
the role of preoperative coronary angiography is still
controversial. The low rate of concomitant coronary
artery disease, the risk of catheter-induced lesions and
management delay are substantial arguments against it.
Angiography may be indicated during or after surgery
(in the era of the hybrid procedures) in patients with
visceral malperfusion and dilatation of the descending
aorta for appropriate treatment guidance9.
Surgical indications and predictors of operative
mortality
As mentioned above, time-honored dictum is that type
A aortic dissection requires urgent surgery. There are,
however, controversial situations where the patients
treatment may stop with medical management: patients with completed stroke, comorbid conditions (e.g.,
cancer, advanced multiple organ dysfunction, advanced age), prior aortic valve replacement (AVR), and
hospital presentation 48 to 72 hours beyond symptoms
onset11. The mortality of untreated ATAAD reportedly
reaches values of 1% to 2%/h in the first 24 hours, up
to 90% of patients succumbing within 30 days. Surgical
repair remains high-risk, with both mortality and neurological complication rates of 15% to 30%. No randomized studies of medical vs surgical management in
ATAAD have ever been performed, but on the available
evidence, surgery converts a 90% mortality rate to at
least a 70% survival rate and no more than 2 patients
need to be treated to gain survival benefit2. Reported
in-hospital mortality for surgically treated cases of
ATAAD varies between 5% and 27.4%, reaching values of 28% in the International Registry of Acute Aortic
Dissection (IRAD) and 17%, respectively, in the German Registry of Acute Aortic Dissection (GERAADA)9.
For patients who present with uncomplicated ATBAD,
the survival rate approaches 90% with medical therapy
alone, while IRAD reported a mortality rate in patients
undergoing surgical repair of 29.3%12. Type II aortic
dissection appears to associate a better prognosis than
Type I, in terms of perioperative, long-term, and aneurysm-free patient survival, related to the propensity
for distal malperfusion phenomena and persistence
of a distal false lumen. Arterial hypertension, although considered one of the most important predisposing
factors of acute aortic dissection, does not seem to influence the prognosis of these patients13. Preoperative
coma, as well as the state of shock secondary to either
cardiac tamponade or coronary dissection and ische

Vol. 24, No. 4, 2014
mia are consistent predictive factors for postoperative

mortality2. In a 2012 study Perrault found cardiogenic
shock, cerebral ischemia and massive hemorrhage to
be responsible for almost 85% of perioperative deaths.
According to Pacini et al., the presence of malperfusion tripled the overall mortality rates associated with
ATAAD (43.7% in the group with malperfusion vs 15%
in that with no malperfusion)10. Another major determinant of outcome in type-A dissection is advanced
age. While ATAAD incidence increases with age, recent studies have highlighted the excessive risks associated in patients over 70 years old5. As with all cardiovascular surgery emergencies, advanced age proved
an independent predictor of worse operative mortality and morbidity and reduced longer-term survival
of ATAAD. However, in western societies one-fifth of
the population are 65 years of age and this fraction is
increasing2. Mehta and associates have shown that the
mortality rate associated with surgery for ATAAD is
45% in patients 80 to 84 years of age and 50% for those
85 or older11. Data from the IRAD registry suggest that
one-third of patients presenting with ATAAD are over
70 years of age, with only 47.6% of those older than 80
years of age undergoing surgery. Surgical mortality for
this group reaches 40%, compared with 58% for the
medically managed patients2. In a 2013 study, Piccardo
reported an overall mortality rate in the group of surgically treated octogenarians with ATAAD of 44.3% and
identified the presence of complications as the only risk
factor for in-hospital mortality. His conclusion was that
octogenarians with uncomplicated ATAAD may benefit from emergency surgical repair14. Our study included 11.72% of patients with ages between the range
of 70 and 96 years old, without significantly increased
mortality rates. Still, the management of acute type A
aortic dissection in these age groups remains controversial14.
All these and other factors have been incorporated
into predictive risk models on the basis of IRAD and
individual center data, which might aid the decision
making process. However, although each complication
might engender additional risk, this does not preclude
a superior outcome with surgery and rigid treatment
exclusion criteria are inappropriate2.
*
The aim of ATAAD surgery is prevention of intra-pericardial rupture, of coronary ostial dissection or aortic valve deterioration, with correction of any of these
when present, correction of distal malperfusion and
permanent obliteration of the distal false lumen (FL).

Vol. 24, No. 4, 2014
This is usually accomplished by ascending aorta replacement accompanied, where possible, by excision
of the proximal entry tear, therefore restoring the dominant true lumen (TL) flow in the distal aorta. Techniques used to achieve these aims have not been subject
to randomized studies so they remain issues of debate2.
Arterial cannulation site
The optimal site of arterial cannulation also remains
controversial. While femoral artery has been the primary site for arterial cannulation in surgery for ATAAD
for a long time2,15, it has lost popularity during recent
years given the worse outcomes it appears to associate
compared to other strategies in contemporary studies9.
Apparently, retrograde perfusion through the femoral
artery may further exacerbate dissected intimal flaps
and determine organ malperfusion, progressive arch
vessel compromise, and neurologic injury and it has
also been associated with a greater stroke risk in patients with concurrent distal aortic aneurysmal or atherosclerotic disease2,15. Previous studies have reported
an incidence of malperfusion syndrome with femoral
cannulation of 2.5% to 13%15. In autopsy series, femoral artery cannulation associated a theoretical potential
for brain malperfusion of 42%, whereas with perfusion
via the axillary artery this potential was limited to only
16%. However, the clinical incidence of these events is
low. Therefore, in ATAAD, initial femoral artery cannulation remains reasonable, if provided malperfusion
monitoring is applied and potential distal aortic pathology is excluded2. Besides the decreased risk of stroke
or malperfusion, the theoretical advantages of axillary
artery cannulation in ascending aorta and arch surgery
include the continuous provision of cerebral flow by
means of selective antegrade cerebral perfusion. The
complications of this technique, such as axillary artery or brachial plexus injury, arm ischaemia and low
CPB flow are becoming well-known, ranging between 0% and 5%15. It remains controversial whether the
axillary artery should be cannulated directly, or using
the sidegraft technique9. In our Institute the primary
arterial cannulation site was chosen according to preoperative imaging techniques and intraoperative findings, thus explaining the variable frequencies between
the axillary and femoral arteries over the years. Central
cannulation is another option, many surgeons preferring to cannulate the dissected aorta itself either with
TTE or TEE guidance or under direct vision after transecting the tourniquet controlled distal ascending aorta, therefore allowing very fast cannulation in an emergency. Left ventricular apex is another potential can-
Ovidiu Stiru et al.

nulation site7. In a 2013 meta-analysis, axillary artery

cannulation seemed to give better short-term mortality
and neurological dysfunction rates than femoral artery
cannulation16. Because no study was a randomized trial
these results are more than uncertain2,16; as the pathoanatomy differs among patients with ATAAD, so does
the optimal cannulation strategy9.
Aortic valve involvement
Approximately 30% of patients with ATAAD have an
aortic diastolic murmur and one-half have aortic regurgitation on ETT, the surgical management of which
is controversial too. Preservation of the native aortic
valve has obvious advantages. In case of normal leaflet
morphology, of flap interference with valve closure or
central regurgitation due to prior dilation of the sinotubular junction, valve competence can usually be restored by re-affixing the commissures to the aortic wall.
However, despite satisfactory early outcomes of this
procedure, 20% to 25% of patients will develop late root
enlargement or progression of aortic regurgitation, necessitating aortic valve replacement or ARR; risk factors
including an aortic annulus of 27 mm in diameter and
above-moderate valve regurgitation at initial surgery.
In patients with pre-existing root pathology VSRR may
be an option, with the added disadvantages of longer
operating times and superior technical requirements.
Of the 2 types of valve sparing root replacement, the reimplantation technique might be superior in ATAAD2.
Kallenbach et al. reported their data after operating
on 295 patients for acute type A aortic dissection with
use of the supracommissural technique, Bentall procedure and valve-sparing reimplantation technique.
In terms of survival and reoperation rates, the authors
concluded that the reimplantation technique yields results comparable to those of the established procedures17. Some centers prefer a more aggressive strategy,
replacing the aortic valve and adding the well-known
risks of prosthetic valves. An aortic root repair (ARR)
procedure could also increase risk in inexpert hands.
Thus, the role of aggressive ARR management of the
aortic valve versus conservative valve re-suspension is
incompletely defined2.
In our series aortic valve involvement reached 37.6%
of cases. A conservative approach was adopted whenever possible and in only 25% of these cases was the aortic valve replaced either isolated or as part of a Bentall
operation. When a competent non-calcified bicuspid
aortic valve (BAV) is detected, the decision to conserve
will depend upon age, presence of annulo-aortic ectasia and degree of aortic root destruction. If the valve
Ovidiu Stiru et al.

is functionally abnormal, but without associated sinus

disease, prophylactic simple aortic valve replacement is
justified. Alternatively, reparative bicuspid valve procedures are well-reported, but their application should be
judicious2. According to Schfers et al., the presence of
BAV does not influences the outcomes of valve-sparing
root replacement (VSRR) procedures. In their series of
153 patients, freedom from reoperation and freedom
from recurrent moderate or severe AR were 95% and
90% respectively after 10 years17. The type of disease
(i.e. valve insufficiency vs stenosis) influences though
the natural history of the aortopathy in BAV patients,
as a history of AVR surgery does too18. Also these patients have a distinctive dissection pattern with the entry
tear frequently located in the aortic root and-despite their younger age-are at risk of substantial hospital
mortality. It has been reported that composite root replacement yields an excellent outcome in BAV patients
suffering from aortic dissection, equal to an age- and
gender-matched normal population19. The routine use
of intra-operative TEE is now regarded as an essential
adjunct2.
Extension of aortic repair
In ATAAD the primary intimal tear is usually present
within the ascending aorta, sometimes accompanied
by secondary, more distal tears. Sometimes, involvement of the ascending aorta can result from retrograde
propagation of the dissection flap with the primary tear
originating within the arch or descending aorta. Occasionally, no intimal tear is identified2. The aortic arch
is dissected in more than 70% of ATAADs. Aortic arch
dilatation or obstruction of the supra-aortic vessels is
common in ATAAD; luminal arch inspection under
DHCA is thus required. The thoracic and abdominal
portions of the descending aorta are involved in 40 and
30% of patients respectively, but are responsible for just
a minority of acute complications. Therefore, the descending aorta itself is not usually treated during emergency surgery for ATAAD. However, in over 70% of patients the FL is chronically perfused, carrying the risk
of further enlargement9. Suboptimal connection of the
distal part of the graft implanted in the ascending aorta to the TL or presence of secondary entry tears may
account for the postoperative persistence of residual
flow into the distal FL. The long-term outcomes of aortic dissections with patent false lumen show a high risk
of complications, sudden death and need for surgery,
particularly from the third year of evolution. In addition to Marfan syndrome, maximum aortic diameter
and the presence of a large, proximal entry tear imply

Vol. 24, No. 4, 2014
a higher incidence of complications during follow-up20.

In the present study an isolated ascending aortic replacement was most often necessary, with an associated
mortality rate of 16.05%, combined with a distally extended aorta replacement in 41% of cases. Aortic arch
and descending aorta replacement were performed with
a frequency of 12.19% and 0.36%, respectively. Both of
them significantly increased mortality rates, reaching
values of 60% and 83.3%, respectively, once more demonstrating that open aortic arch reconstruction remains a formidable operative procedure, recommended
only in highly experienced centers. Probably in association with these complex procedures prolonged CPB
time also significantly increased mortality rates: a CPB
duration of 400 minutes or longer related to a mortality
rate of 82.46%. Recently published results indicate that
the dreaded complications of arch repair, namely death
and stroke, can occur at rates under 5% in these experienced centers. Himanshu and Deeb reported in a 2013
study on 721 patients with open arch reconstruction a
mortality rate of 21.6%21. Novel hybrid techniques have
been developed in the treatment of ATAAD with arch
involvement. A recent prospective study on the use of
hybrid operating rooms for the management of acute
dissection demonstrated that a hybrid OR enabled the
identification of downstream malperfusion sites, 23%
of patients requiring primary endovascular intervention and 35% requiring descending aortic repair in addition to ascending aortic replacement10. The elephant
trunk is the classical extension of the aortic arch replacement into the descending aorta. During arch replacement, the distal end of the aortic graft is advanced into
the descending aorta and connected to the distal aorta
in a second procedure. This technique has been refined
by the use of stent-graft-reinforced hybrid prostheses
which are implanted into the descending aorta in an
antegrade fashion during arch replacement (frozen
elephant trunk), leading to high false-lumen occlusion
rates5,9. However, thoracic endovascular aortic repair
(TEVAR), subject of the INSTEAD trial, has become
the standard treatment for several descending aorta
pathologies. In malperfusion syndromes resulting from
dynamic true-lumen compression through a dead-end
false lumen, fenestration of the dissection membrane
is regarded as a complementary treatment. Today, the
method has mostly been replaced by TEVAR9. Operative mortality for acute type A dissection is multifactorial, but remains poorly elucidated10. Although on a descending trend over the last nine years, mortality rates
in this study maintain at high levels. Overall, except in
Ovidiu Stiru et al.


Vol. 24, No. 4, 2014
highly specialized centers, surgical outcomes might be

static, and there is abundant room for improvement2.
CONCLUSIONS
Acute type A aortic dissection is a frequent pathology
in the cardio-vascular surgical area. Moreover it can
prove to be a surgical challenge, with increased morbidity and mortality rates, particularly in extended, complicated forms. The rapidity of diagnostic confirmation
and institution of treatment are essential in these cases.
Surgical techniques have diversified and improved, especially in the field of aortic valve and root reconstruction and in the field of cerebral protection enabling
more extensive aortic arch surgery and lowering morbidity and mortality rates. Endovascular strategies are
also emerging, apparently with favorable results. Surgical treatment of ATAAD remains controversial, but in
experienced centers the results appear to be more than
satisfying.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Note: This work received financial support through the

project CERO - CAREER PROFILE: ROMANIAN
RESEARCH, contract no. HRD / 159 / 1.5 / S / 135760,
financed from the European Social Fund through the
Sectorial Operational Programme Human Resources
Development 2007-2013
Authors contributions: All authors have contributed
to the manuscript and approved the final version.
14.
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Piccardo A, Le Guyader A, Regesta T, Gariboldi V, Zannis K, et al. Octogenarians with uncomplicated acute type a aortic dissection benefit
from emergency operation, Ann Thorac Surg., 2013; 9: 851-856.
Lee HK, Kim GJ, Cho JY, Lee JT, Park I, et al. Comparison of the Outcomes between Axillary and Femoral Artery Cannulation for Acute
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ORIGINAL ARTICLES
Predictive value of exercise stress testing in a tertiary

cardiological center
Daniel Gherasim1, Maria Jalb1, Marina Lupu2, Dan Deleanu1, Carmen Ginghin1,3, Eduard Apetrei1,3
Abstract:
Purpose Exercise stress testing (ET) is a valuable screening test for the detection of obstructive coronary artery
disease (CAD). Previous studies from the literature show an overall sensitivity of 68% and specificity of 77% with variable
predictive values depending on pretest probability. The purpose of the current study was to evaluate the diagnostic value of
ET in the modern era of cardiology. Aims This is a retrospective study on 404 patients with chest pain suggestive for angina
and with no history of ischaemic heart disease, which have performed a treadmill exercise stress testing and than after and a
selective coronary angiography, from October 2008 to January 2013. The coronary angiography was performed between 2 60 days after the test. A positive test was defined as horizontal or downsloping ST segment depression or elevation of 0.1 mV
(1mm) or slowly upsloping of 1.5 mm (the slowly upsloping was defined as <1 mv/s). Coronary arteries stenoses were quantitatively evaluated and considered significant if the coronary diameter was reduced by 70%. Results From 404 patients,
254 were men (63%) and the average age was 59.3 years 9 years. Hypertension was found in 80.7% (326 patients), diabetes
in 23.2% (94 patients), 48.5% were smokers (196 patients), 82.1% had dyslipidemia (332 patients) and 30.7% were overweight
(124 patients). A positive stress test was found in 285 patients and 186 had significant stenosis on coronarography. The rest of
119 patients had either a negative stress test, an equivocal one or inconclusive (the inability to reach 85% of the target heart
rate, and without any ST segment alterations). At the coronary angiography we found significant lesions in 32 patients (26.9%)
from the group with negative, equivocal or inconclusive stress testing. The sensitivity of the test was 85.3% and the specificity
46.8%.The positive predictive value was 65.3% and the negative predictive value was 73.1%. The amplitude of ST segment
changes showed a correlation with the degree of stenosis. No correlation was found between the ECG teritory were ST depression appeared and the affected coronary artery, but ST elevation in lead aVR is an important indicator of significant left main
coronary artery (LMCA) stenosis.The time of exercise (the exercise capacity) is correlated with the age of the patient. Conclusions In modern era where imagistic stress testing seems to have a better sensitivity, the old fashioned electrocardiographic
stress test continues to have a good sensitivity and remains, due to the larger accessibility and lower cost compared with other
techniques (stress echography, stress SPECT, myocardial perfusion imaging) the first option in the diagnostic algorithm of
coronary artery disease.
Keywords: exercise testing, risk factors, predictive value, significant coronary artery stenosis, exercise capacity.
Rezumat: Scopul Testul ECG de efort reprezint o metod valoroas i larg folosit pentru diagnosticul bolii obstructive
coronariene. Studiile anterioare din literatura de specialitate artau o sensibilitate de 68% i o specificitate de 77% pentru testul
de efort, valoarea predictiv depinznd de probabilitatea pretest pentru boal coronarian. Scopul studiului este de a evalua
valoarea diagnostic a testului de efort n epoca cardiologiei moderne. Metoda Am efectuat un studiu retrospectiv pe 404
pacieni care prezentau durere toracic sugestiv pentru angin, fr boal coronarian ischemic cunoscut, care au efectuat
un test de efort pe covor rulant n laboratorul nostru i apoi control coronarografic, n perioada octombrie 2008-ianuarie
2013. Coronarografia a fost realizat ntr-un interval cuprins ntre 2 i 60 de zile dup test. Testul a fost interpretat ca pozitiv
dac a aprut subdenivelare de segment ST de minim 0,1 mV (1 mm) de tip orizontal sau descendent sau subdenivelare de
tip lent ascendent 1,5 mm sau supradenivelare de segment ST de minim 0,1 mm. Stenoza coronarian a fost interpretat ca
semnificativ la o reducere a lumenului 70%. Rezultate ntre cei 404 pacieni, 254 erau brbai (63%), iar vrsta medie a
grupului a fost de 59,3 ani 9 ani. Ca factori de risc, 80,7% (326 de pacieni) aveau hipertensiune, 23,2% (94 pacieni) erau
diabetici, 48,5% (196 de pacieni) erau fumtori, 82,1% (332 pacieni) aveau valori mari ale colesterolului seric, iar 30,7% erau
supraponderali. Testul a fost pozitiv la 285 de pacieni iar o stenoz semnificativ a aprut n 186 de cazuri. Restul de 119 pacieni au avut fie un test negativ, fie un test interpretat ca echivoc (modificri ale segmentului ST sub limita pragului ischemic
stabilit) sau neconcludent (nu a realizat un test submaximal, adic 85% din valoarea maxim predictiv pentru vrst). Sen-
Prof.Dr. C.C. Iliescu Emergency Institute for Cardiovascular Disease,

Bucharest
2
Panduri Medical Center, Bucharest
3
Carol Davila University of Medicine and Pharmacy, Cardiology Department, Bucharest
Contact address:
Dr. Daniel Gherasim, Clinical Cardiology, Prof. Dr. C. C. Iliescu Emergency Institute for Cardiovascular Disease, Bucharest, Sos.Fundeni 258,
Sector 2, Bucharest, Zip code 022328
E-mail: gherasimdanro@yahoo.com
Daniel Gherasim et al.

Predictive value of exercise stress testing

Vol. 24, No. 4, 2014
sibilitatea testului a fost de 85,3%, iar specificitatea de 46,8%. Valoarea predictiv pozitiv a fost de 65,3%, iar cea negativ de
73,1%. Amplitudinea modificarilor ST s-a corelat cu gradul stenozei. Nu a putut fi stabilit o corelaie ntre teritoriul n care au
aprut modificrile pe ECG i artera coronar implicat, exceptnd supradenivelarea segmentului ST n aVR care reprezint
un indicator pentru stenoza de trunchi comun. Timpul de efort (capacitatea de efort) este corelat cu vrsta. Concluzii n
epoca cardiologiei moderne, cnd sunt disponibile alte investigaii noninvazive cu sensibilitate superioar (ecografia de efort,
perfuzia miocardic de stress), testul de efort continu s arate o bun sensibilitate i rmne, datorit costului redus i accesibilitii, prima opiune n algoritmul de diagnostic al bolii coronariene.
Cuvinte cheie: test de efort, factori de risc, valoare predictiv, stenoz coronarian semnificativ, capacitate de efort.
INTRODUCTION
Cardiovascular disease (CVD) remains the global main
cause of death, accounting for 17.3 million deaths per
year and continues to cause a much greater mortality
burden among Europeans than any other disease: 51%
of deaths among women and 42% among men in the
last year of reported data1. Coronary heart disease only,
accounts for almost 1.8 milion deaths, or 20% of all
deaths in Europe annualy, but the patterns vary widely
in individual countries2. In our country, age-standardized mortality is still high, despite a decrease of mortality rate in the last 10 years with 16% in men and 22%
in women2.
Chest pain is the most common presenting complaint indicating CAD and is seen frequently by primary
care physicians or cardiologists.
The exercise treadmill test is used in the evaluation
of symptomatic patients to predict the presence and extent of coronary artery disease (CAD). A large number
of noninvasive stress testing are currently available, but
the exercise ECG is still used as a standard for comparison with other clinical and testing risk markers. It is
also the least costly of all provocative noninvasive tests,
do not always require a cardiologist, and are convenient
for the patient because are often an office-based investigation. The ECG exercise test (ET) for the diagnosis of
obstructive CAD has a class I indication (class I: conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and
efective) in the subgroup of adults with an intermediate
pretest probability of CAD on the basis of gender, age,
and symptoms3.
The studies evaluating the diagnostic accuracy of
the ET have proved a mean sensitivity of 68% and a
mean test specificity of 77%, with sensitivities ranging
from 23% to 100% and specificities ranging from 17%
to 100%, but the large proportions of studies and metaanalysis was published about 20 or 30 years ago4. The
prevalence of CAD was changing and also, over the
past two decades the frecquency and severity of abnormal stress testing have progressively decreased5. In the
modern era of cardiology, to analyse the sensitivity and

specificity of ECG exercise testing could be a challenge.
In our knowledge, there are no available data regardind the sensitivity or specificity of ET nowdays in our
country.
STUDY GROUP
This is a retrospective study of 404 patients, which were
referred for exercise testing in our Institute between October 2008 to January 2013, according to the following
inclusion criteria: 1) chest pain suggestive for angina;
2) no history or electrocardiographic evidence of previous myocardial infarction; 3) no left bundle branch
block, WPW syndrome, ECG criteria for left ventricular hypertrophy (LVH) or valvular disease which can
influence the interpretation of ST segment deviation or
left ventricular function; 4) absence of clinical indication for urgent coronary revascularization.
Clinical informations and risk factors evaluation
were obtained before testing. Exercise testing was performed in the morning and after withdrawal, where
was the case, of antianginal therapy for at least 72 hours, on the treadmill (Burdick, USA) using the classical Bruce protocol under supervision of the in charge
cardiologist; recording of the ECG was done with the
Mason-Likar torso-mounted limb system, ankle and
wrist electrodes being replaced by electrodes mounted
on the torso at the base of the limbs. The patients were
encouraged not to tighly grasp the front or side rails of
the treadmill and to exercise to their maximum. The
test was symptom limited and was terminated when
any of the following occurred: severe angina, dyspnoea,
fatigue, hypotension, complex ventricular arrhythmia
and >1 mm ST segment depression. Sub-maximal predicted heart rate was calculated as 75% of maximal predicted heart rate (ie 220-age). The ECG was recorded
with a Siemens Megacart electrocardiograph on each
stage, prior peak exercise and in the recovery period,
at each minute. A paper spead of 25 mm/s was used
an 1 vertical mm equals 0,1 mV. The ECG was read by
measuring the ST segment deviation from the PQ (PR)

segment at 0,08 sec. from the J point. A positive test

was defined as horizontal or downsloping ST segment
depression or elevation of 0,1 mV (1 mm) or slowly
upsloping of 1.5 mm, slowly being defined as <1 mv/
sec. Equivocal test was defined as not meeting the positive test criteria but showing concerning change (eg,
minimal ST depression not reached 0,1 mV, symptoms
of chest pain without ECG changes). Inconclusive tests,
the inability to achieve 85% of the maximal predictive
heart rate, were assimilated with the equivocal tests. ST
deviation was interpreted by the treadmill computer
system, with confirmation or regulation by the supervising physician (cardiologist with great experience in
ET). All the ET data were abstracted from the standard
ET template routinely used in our system.
Systolic blood pressure was measured with a mercury sphygmomanometer in the final minut of each
stage, at peak exercise and immediately after stoping
exercise and every minut in the recovery phase. Exercise capacity was estimated from the time of exercise.
Selective coronary angiography was performed between 2 days and 60 days after the test, the decision to
referre the patient for invasive evaluation had belonged
to the attending cardiologist. Coronary artery stenoses
were quantitatively evaluated and considered significant if the coronary diameter was reduced by 70%.
Data collected on each patient included age; sex; risk
factors for CAD; exercise time; the maximum amplitude of ST segment deviation (mm); the ECG leads with
ST deviation which were grouped in five teritories: I,
aVL, V4-V6; V3-V5; II, III, aVF; aVR, V1; V4-V6; the
degree of stenoses for left anterior descending artery
and the septal and diagonal branches (LAD), left circumflex artery and his marginal branches (Cx), right
coronary artery (RCA) and left main coronary artery
(LM).
STATISTICAL ANALYSIS
Descriptive statistics were used to characterize the
study population with respect to demographics, cardiac risk factors and ET results. We then evaluated the
relationship between ET results and documented extend of CAD in coronary angiography by calculating
sensitivity, specificity, predictive positive value (PPV),
negative predictive value (NPV) using standard formulas from 2x2 table. The analysis was performed using
SPSS 21.0 (Statistical Package for Social Science version
21, SPSS, Inc, USA). The Spearman correlation coefficient was used to determine bivariate non-parametrics
correlations. A probability error of 5% was established

Vol. 24, No. 4, 2014
for every analysis, the value of p<0.05 being considered

statistically significant.
RESULTS
Patient demographics of the 404 patients are presented in Table 1. Sixty-three percent were men and 37%
were women. The age range from 28 to 83 years with a
mean age of 60 years 9 (mean standard deviation),
the same mean value for men, as for the women. The
study population has a significant number of cardiac
risk factors, as noted in Table 1. Hypertension was present in 326 patients (80.7%),and dyslipidemia in 82.2%
(332 patients); 196 patients had declared to be active
smokers (48.5%), 124 patients (30.7%) were overweight persons, and the diabetes was found in 94 cases
(23.3%). 37,6% of patients had 2 risc factors and 36.6%
presented the association of three risk factors.
There were a total of 285 positive tests and 119 negative tests, which includes also the equivocal tests. A
significant coronary artery stenosis was present in 186
patients with positive stress testing and in 32 patients
with negative stress testing, as shown in Figure 1. The
ST segment depression was recorded simultaneously in
leads I, aVL, V4-V6 in 50 patients, in leads V3-V5 in
136 patients, in inferior leads II, III and aVF in 201 patients (50% of total patients), in V4-V6 in 185 patients.
ST segment elevation in aVR and V1 was recorded in
65 patients. The ST deviation was recorded in two ECG
territories in 122 patients (30.2%).
The sensitivity of the test was 85.3%, the specificity
46,8 %, the positive predictive value was 65.3%, and the
Table 1. Characteristic of the Exercise Stress
Testing Study Population
Age (years)
Mean
SD
Sex (%)
Men
Women
Risk Factors (%[n])
Hypertension
Hypercholesterolemia
Diabetes Mellitus
Current smoker
Obesity
Association of Risk Factors (%[n])
No risk factors
One risk factor
Two risk factors
Three risk factor
Four risk factors
All five risk factors
59.3
+/- 9
63
37
80.7 (326)
82.1 (332)
23.2 (94)
48.5 (196)
30.7 (124)
1.5 (6)
6.7 (27)
37.6 (152)
36.6 (148)
14.6 (59)
3 (12)


Vol. 24, No. 4, 2014
Figure 1. The prevalence of significant coronary artery stenoses.
negative predictive value was 73.1%. Both sensitivity

and specificity were similar in men and women (0.87
and 0.46 for men, respectively 0.78 and 0.47 for women). The PPV was greater for the men (0.75 vs 0.44
in women), but NPV was greater for the women (0.8
vs 0.66 for men), which corresponding with the higher
prevalence of CAD in men compared with women in
the same aging group. Most patients (29%) had only
one coronary artery with stenosis; the sensitivity of the
ET for the one-vessel disease was 74.5%, and specificity
was 50%. If the equivocal test would be included in the
positive tests, the sensitivity of the test would be 94.5%,
with a decrease in specificity (31.2%); PPV would be
61.7%, and NPV 82.9%. We found, also, a high sensitivity (91.5%) and a low specificity (37%) when we made
the calculation without take into account the equivocal

tests, comparing only positive with pure negative tests.
For a better comparison between the results of ET
and coronary arteries involvement, we have divided
the study population in four groups: 1) patients with
positive ET and significant coronary lesions - true positive tests (186 patients); 2) patients with positive ET
and without significant coronary artery stenosis - false
positive tests (99 patients); 3) patients with negative or
equivocal ET and without coronary stenoses - true negative tests (87 patients); 4) patients with negative ET
and significant coronary stenosis - false negative tests
(32 pacients). The characteristics of the four groups are
presented in Table 3.
A pure negative ET (equivocal test not included) was
recorded in 65.5% (57 patients) with no coronary artery stenoses and only in 13 patients (40%) in whom
the CAD was present. In 32 patients with significant
stenosis the ET was not positive. In these patients, the
majority (25 patients) had one vessel disease (any coronary artery), one patient had three vessels disease and
one patient had significant stenosis of left main artery,
but also of LAD and Cx.
The ECG teritory with ST deviations (anterior, inferior, antero-septal, lateral) is not specific for one or
other of the coronary artery, except the ST depression
in V3-V5 or ST elevation in aVR, V1 where odds ratio
(OD) for the LM is statistically significant, as shown in
Table 2.
Table 2. The distribution on ECG territories compared with the involved coronary artery
I, aVL,V4-V6
V3-V5
II, III, aVF
aVR, V1
V4-V6
LAD
Cx
RC
LM
LAD
Cx
RC
LM
LAD
Cx
RC
LM
LAD
Cx
RC
LM
LAD
Cx
RC
LM
No (%)
OR
33 (66%)
27 (54%)
26 (52%)
7 (14%)
54 (39.7%)
38 (27.9%)
42 (30.9%)
12 (8,8%
98 (48.8%)
79 (39.3%)
95 (47.3%)
21 (10.4%)
41 (63.1%)
36 (55.4%)
34 (52.3%)
18 (27.7%)
89 (48.1%)
74 (40%)
83 (44.9%)
16 (8.6%)
3.556
3.603
2.676
2.343
1.038
0.980
0.946
1.344
2.268
3.108
4.617
2.515
3.241
4.154
2.859
10.436
2.015
2.983
3.146
1.386
95% Confidence Interval

1.905
1.964
1.468
0.949
.681
.619
.606
.628
1.506
1.960
2.902
1.122
1.868
2.395
1.663
4.728
1.344
1.899
2.032
.658
6.640
6.607
4.880
5.784
1.584
1.550
1.476
2.878
3.414
4.930
7.346
5.635
5.625
7.204
4.914
23.037
3.023
4.687
4.873
2.922
No=number of cases with coronary arteries stenoses; OR = odds ratio


Vol. 24, No. 4, 2014
Table 3. Characteristics of The Exercise Testing Groups According with the Positivity of the Test and Presence of Significant Coronary
Arteries Stenoses
No. of patients
Mean age (years)
Women (no, [%])
Risk factors
1
2
3
4
Mean exercise time (min)

Mean ST segment deviation (mm)
Positive test,
signifiant stenoses
Positive test, no
signifiant stenoses
Negative test, no
signifiant stenoses
Negative test,
signifiant stenoses
186
60.2
41 (22%)
99
59.8
52 (52%)
32
61
11 (34%)
64 (33.4%)
78 (41.9%)
32 (17.2%)
6.2
1.65
44 (44.4%)
34 (34.3%)
11 (11.1%)
6.68
1.28
87
56.3
46 (53)
15 (17%)
30 (34.5%)
28 (32%)
7 (8%)
7.15
-
The most significant stenoses were found in patients

in whom the ST segment alteration in lateral leads V4V6 or aVR and V1 have been revealed. In Figure 2 we
have presented the exercise electrocardiogram of a patient with severe stenosis located at the ostium of LAD,
with ST depression in multiple leads, but also with ST
elevation in aVR.
When we analysed the correlation between the number of risk factors for CAD and the number of involved
coronary arteries, an correlation Spearman coefficient
of 0.210 was positive, indicating a positive relation, but
A.
14 (43.7%)
8 (25%)
8 (25%)
6.24
-
the power of this indicator is weak. More risk factors

we have, more coronary artery with stenosis will be
found (p<0.05). For each unit increase in number of
risk factors, the number of affected coronary arteries
will increase with 0.245; eg, the predictor number of
stenotic coronary arteries will be 1.8 in a patient with
all five risk factors.
The exercise capacity, expressed as exercise time on
treadmill is not correlated with the number or the degree of coronary artery stenosis. The age of the patient
was the only factor which we could find to significant
B.
C.
Figure 2. A. Rest Electrocardiogram(ECG) normal; B. The positive exercise test: ST depression in leads II, III, aVF, V3-V6 and ST segment elevation in
aVR; C. The coronary arteriography: suboclusion located at the ostium of LAD. ( LM - left main coronary artery, LAD - left anterior descending, CX - left
circumflex artery).


Vol. 24, No. 4, 2014
influence the exercise capacity.

The amplitude of ST modification was correlated
with the severity of coronary artery stenosis.
Hypertension was the risk factor we have found in
325 patients. In this subgroup of patients, the ST segment alterations was recorded predominantely in the
lateral precordial leads V4-V6. The exercise time was
almost one minut better (52 sec) in hypertensive patients with a stenosis <70% or without stenosis, compared with the hypertensive patients with significant stenosis, which is statistically significant (p<0.0001). The
same correlation was found when we analised the exercise capacity and the results of ET. The hypertensive
patients with positive ET had a lower exercise capacity
(difference of 54 sec) when the stenosis is <70% compared with hypertensive patients with positive ET and
stenosis >70% (346 sec vs 400 sec), as shown in Table 5.
DISCUSSION
Exercise testing remains the most widely accessible and
relatively inexpensive method for initial evaluation of
suspected coronary artery disease6. Prediction of the
disease is one of the primary functions of stress testing
and any clinician would like to be able to predict in each
patient the anatomic and functional coronary disease
severity, which influence the ultimate outcome of the
patient7. Bayess theorem states that the predictive value of a positive test is directly related to the prevalence
of disease in the population being studied3,7. There are
a number of ways to estimate disease prevalence, and
therefor is a disagreement in this field. Also, there are
diferences between prevalence of CAD in diferent areas
of cardiology practice; would be a larger percentage of
patients with CAD in a tertiary center with experts in

the field than in the office of GP, for example. The sensitivity of the ET is not very good compared with other
noninvasive methods such as the various exercise imaging studies which provide greater diagnostic accuracy
than electrocardiograhic test alone.
ECG for the detection of CAD revealed a mean test
sensitivity of 68% and a mean test specificity of 77%8,
but the data were recorded almost three decades ago,
even they are mentioned in recent papers and scientific
statements for clinical practice4.
We found a high sensitivity (85.3%), a specificity of
46,7% and NPV of 73,1% in our study, which is comparable with much expensive tests used to diagnose the
presence of coronary artery disease. For example, the
exercise stress echocardiography has a sensitivity of
80-85%, and a specificity of 80-88%; the exercise stress
SPECT (single photon emission computed tomography) has a sensitivity of 73-92%, and a specificity of
63-87%9. We didnt have collected data about pretest
probability and usually, the pretest probability is formally estimated, based on symptomatology, age and
sex, as noted in the ACC/AHA Guideline for stess testing3 (Table 4). We can presume that a large number of
patients has an intermediate to high pretest probability,
being selected by general practician (GP) and attending
cardiologist, but was the same ET laboratory status as
shown in previous studies. Certainly, the study has a
referral bias (RB) which occurs when patients with an
abnormal stress test result are referred to cardiac catheterization at a higher rate than those with a normal
stress result, but usually RB is not accounted for when
analysing the sensitivity and specificity of stress test.
Table 4. Pretest Probability of Coronary Artery Disease by Age, Gender, and Symptoms
Age (years)
Gender
Typical Angina
Atypical Angina
Nonanginal chest pain
Asymptomatic
30-39
Men
Women
Men
Women
Men
Women
Men
Women
Intermediate
Intermediate
High
Intermediate
High
Intermediate
High
High
Intermediate
Very low
Intermediate
Low
Intermediate
Intermediate
Intermediate
Intermediate
Low
Very low
Intermediate
Very low
Intermediate
Low
Intermediate
Intermediate
Very low
Very low
Low
Very low
Low
Very low
Low
Low
40-49
50-59
60-69
Modified from refs.3

High indicates > 90%; intermediate, 10% - 90%; low, <10%; very low, <5%. Intermediate pretest probability is an ACC/AHA Class I indication for exercise testing.
Table 5. Exercise Capacity and the Severity of Stenosis in Hypertensive Patients

Group Statistics
Exercise
Time (sec)
Coronary stenosis
No
Mean
Std. Deviation
Std. Error Mean
>70 %
<70%
118
102
348.3136
400.4216
109.17708
79.60029
10.05057
7.88160

Despite the fact known from old studies that ST depression is less likely to be associated with CAD in women10,11, we found a high sensitivity for ET in women
too (0.78%). The PPV was 0.44% (compared with 0.75
in men), but the NPV is superior in women (0.8 vs 0.66
in men). The difference could be explained by the diferences in the prevalence of CAD in women vs men12.
As we expected, we didnt find a correlation between
the ECG leads with ST changes and the coronary artery involved. When LAD disease was found, in 66% of
cases the ST depression had occurred in anterior leads
I, aVl, V4-V6, but for the same disease we found ECG
changes also in V3-V5 in 40% of cases, only in V4-V6
in 48%, and the same prevalence in inferior leads (48%
of cases). In many cases we had concomitant ST changes in more then one territory. The ecg changes was
occurred in one territory in 23% of cases. But the amplitude of ST depression was correlated with the degree
of stenosis: more tight stenosis we had, more depth ST
modification.
A challenging issue in the literature was the predictive value of ST elevation in lead aVR in the setting of
exercise testing. Prior studies have demonstrated the
value of ST changing in aVR in acute coronary syndromes where the ST elevation may indicate severe stenosis or occlusion of the left main coronary artery13-15. In
the setting of ET only few studies16-18 raised the importance of ST elevation in aVR as an important indicator
for significant LM stenosis or ostial LAD stenosis. In
our study, the ST changes in aVR and V1 were statistically significant marker for the LM stenosis.
We found hypertension in 80.7% of cases, which
is the double of the prevalence found in the SEPHAR
II study, where the prevalence of hypertension was
40.1%19. Exercise responses regarding exercise BP, exercise capacity, ST changes in hypertensive patients are
correlated with the risk of CV disease and CV death20,21.
In our study, the hypertensive patients developed ST
segment depression predominantely in the lateral precordial leads V4-V6, a fact which was revealed also in
other ET studies22, and had a lower exercise capacity
(they didnt reach the stage III of the Bruce protocol) if
a significant coronary artery stenosis occurred.
We note also that the exercise testing is a safe procedure. There were no serious complications in this study,
even in the patients with severe CAD.
Conclusions. In the modern era with dynamic changes in the prevalence, impact and treatment of cardiovascular risk factors and changes in the prevalence of
CAD and CVD mortality, the predictive value of ECG

Vol. 24, No. 4, 2014
stress testing is not very well established. We have demonstrated that in a specialised cardiological center,
with a high expertise in ET, the sensitivity of the exercise testing for CAD is also high, both in men and women, comparable or even superior with other imaging
exercise techniques; exercise testing continue to be first
option in the diagnostic algorithm of coronary artery
disease and with a good price/quality ratio.
Conflic of interest: The authors declare that they dont
have any conflict of interest.
Authors contributions: All authors have contributed
to the manuscript and approved the final version.
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REVIEWS
Dillemas in the use of therapeutic hypothermia after cardiac

arrest
Doron Zahger
BACKGROUND
Sudden cardiac death is a leading cause for mortality
and severe disability worldwide. Survival following out
of hospital cardiac arrest remains very low, in the range
of 5-10%1 and many survivors are left with significant
neurological impairment. Most patient who die after
out of hospital cardiac arrest die as a direct consequence of the neurological insult.
Hypothermia has long been known to be associated
with better outcome following drowning and was used
to protect the brain during cardiac and brain surgery.
In 2002 two pivotal trials were published which demonstrated the ability of mild therapeutic hypothermia
(MTH) to improve survival and neurological outcome
following out of hospital cardiac arrest2,3. Since then,
MTH was recommended by the resuscitation guidelines and adopted in many centers. However, important
questions remain concerning the use of this modality
in real practice. This brief review highlights the main
current dilemmas in the field.
THE PIVOTAL TRIALS

The European HACA investigators randomized 275
patients with out of hospital cardiac arrest due to ventricular fibrillation (VF) to either MTH or standard
treatment. Cooling was achieved in hospital by means
of ice packs and cooling blankets and treatment was
given for 24 hours. Bernard and co workers from Australia randomized 77 survivors of out of hospital VF
to MTH or standard treatment. Cooling was started
pre hospital and achieved by ice packs. In both trials
the experimental arm involved cooling to 32-34 degrees. The HACA trial showed a significant reduction in
mortality and neurological disability in the MTH arm.
The smaller Australian trial could only show improved
neurological outcome. A meta analysis of the rando-
Soroka University Medical Center Faculty of Health Sciences, Ben Gurion

University of the Negev
mized trials showed a significant 68% increase in the

rate of survival with favorable neurological outcome at
hospital discharge4.
QUESTION 1: Should MTH be applied regardless of
initial rhythm?
Both seminal trials which examined the role of MTH
following cardiac arrest included only patients whose
initial rhythm was VF. It is well documented that patients with non shockable rhythms on presentation have
a much worse prognosis than patients presenting in VF,
probably reflecting a longer time to initiation of resuscitation and/or more profound myocardial damage5.
A number of registries examined the role of this treatment among patient initially presenting with non shockable rhythms (asystole or pulseless electrical activity).
In a large French registry Dumas et al. compared the
effects of MTH among patients who presented with VF
or with a non shockable rhythm6. Among 1145 patients
admitted after out of hospital cardiac arrest 457 received MTH after an initial shockable rhythm. Of those,
44% had a favorable neurological outcome compared
to just 15% of patients who received MTH after presenting with a non shockable rhythm. In a multivariate
analysis MTH predicted better outcome only among
patients presenting with a shockable rhythm but seemed ineffective among others. Sandroni al performed
a meta analysis of all studies which examined the effect
of MTH after non VT/VF cardiac arrest7. Their results
showed a very small, but significant benefit of treatment
in this population. However, the quality of the data was
very poor and was based mostly on observational data.
In summary: MTH does not seem harmful in patients who initially presented with a non shockable
rhythm. The prognosis of these patients is very poor
Contact address:
Doron Zahger, MD
Department of Cardiology, Soroka University Medical Center
Faculty of Health Sciences, Ben Gurion University of the Negev
Beer Sheva, Israel. Email: dzahger@bgu.ac.il
Doron Zahger

Vol. 24, No. 4, 2014
and might be improved very slightly with MTH. Until

larger randomized trials are available the decision regarding MTH should be individualized based on all relevant factors such as the patients age, time to initiation
of CPR, time to return of spontaneous circulation and
neurological status on admission. Current guidelines
provide similar recommendations.
QUESTION 2: Should MTH be started pre hospital?
As mentioned above, the Australian study used pre
hospital cooling while in the European trial cooling
was initiated in the Emergency Department. Pre hospital cooling is logistically challenging but animal data
suggest earlier cooling may improve outcome. Wolff
et al.8 examined the relation between time to achievement of target temperature and outcome and showed
that neurological outcomes were better among those
patients in whom target temperatures were achieved
faster. Bernard and co-workers randomized 234 patients after cardiac arrest to pre hospital or in hospital
cooling9. Neurological outcomes did not differ significantly between groups. Similarly, a meta analysis of
all studies available until 2013 failed to show an effect
of pre hospital cooling on survival after cardiac arrest
as compared to in hospital cooling10. Finally, Kim et al
randomized 1364 survivors of out of hospital cardiac
arrest to pre hospital or in hospital cooling and could
not demonstrate any beneficial effect of the earlier intervention, even though core temperature was reduced
earlier in the intervention group11.
In summary: there is no justification to routinely initiate MTH in the pre hospital cooling, especially considering the substantial logistical difficulties involved.
Whether such intervention might be justified when
evacuation times are very prolonged remains to be determined.
QUESTION 3: What should the target temperature be?
The initial trials of MTH compared cooling to 32-34
degrees Celsius to no cooling. More recently, the Targeted Temperature Management trial randomized 939
patient after out of hospital cardiac arrest to receive either cooling to 32-34 degrees or to a milder form of
temperature control of 36 degrees12. To the surprise of
many, despite the achieved difference in body temperature according to the protocol no significant differences
were found in survival or neurological outcome between groups. The reasons for this surprising finding are
incompletely understood. First, it is important to realize
that the experimental arm in this study included a mild

form of temperature control and is not the equivalent
of no cooling. Conceivably, it might be more important
to prevent hyperthermia, which is common after cardiac arrest, than to induce hypothermia. Another important might be the fact that in this study the median
time to initiation of bystander CPR was only 1 minute.
This very fast response might have resulted in a generally better neurological outcome and it might therefore have been harder to show an effect of hypothermia.
However, the time to return of spontaneous circulation
in this trial was about 25 minutes, similar to the initial
studies of MTH. Furthermore, this study of 939 patients
is much larger than all previous studies combined and
its results appear robust. Following this study ILCOR
has issued a statement that until more thorough review
of the data is performed clinicians should adhere to the
previous recommendation (i.e. cooling to 32-34 degrees) but the committee recognized that some clinicians
may choose to follow the milder form of temperature
controlled suggested by this trial.
In summary: The results of the TTM trial justify
using a milder protocol of hypothermia, as done in this
trial. Whether patients with longer delays to initiation
of bystander CPR might benefit from more profound
cooling remains to be seen.
SUMMARY
The key to improve survival after out of hospital cardiac arrest is rapid CPR and defibrillation. MTH has
an important role in minimizing neurological outcomes and improving survival. Cooling should be started in comatose patients initially presenting with VF or
pulseless VT while the benefit among patients with an
initially non shockable rhythm is questionable. MTH
should generally be instituted in hospital. Good evidence supports a target temperature of 36 degrees as
done in the TTM trial. Ongoing trials are expected to
clarify further these critical questions in the application
of MTH after cardiac arrest.
Conflict of interest: none declared
References
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3.
Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of

out-of-hospital cardiac arrest and survival rates: Systematic review of
67 prospective studies. Resuscitation. 2010 Nov;81(11):1479-87
The Hypothermia after Cardiac Arrest Study Group. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac
Arrest. N Engl J Med 2002; 346:549-556.
Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge
G, Smith K. Treatment of Comatose Survivors of Out-of-Hospital
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M; Collaborative Group on Induced Hypothermia for Neuroprotection After Cardiac Arrest. Hypothermia for neuroprotection after
cardiac arrest: systematic review and individual patient data metaanalysis. Crit Care Med. 2005 ;33(2):414-8.
Holmgren C1, Bergfeldt L, Edvardsson N, Karlsson T, Lindqvist J,
Silfverstolpe J, Svensson L, Herlitz J. Analysis of initial rhythm, witnessed status and delay to treatment among survivors of out-of-hospital cardiac arrest in Sweden. Heart. 2010 Nov;96(22):1826-30.
Dumas F, Grimaldi D, Zuber B, Fichet J, Charpentier J, Pne F, Vivien
B, Varenne O, Carli P, Jouven X, Empana JP, Cariou A. Is hypothermia after cardiac arrest effective in both shockable and nonshockable
patients?: insights from a large registry. Circulation. 2011 Mar 1;123
(8):877-86.
Sandroni C, Cavallaro F, Antonelli M. Therapeutic hypothermia: is it
effective for non-VF/VT cardiac arrest? Crit Care. 2013 Mar 19;17(2):
215.
Wolff B, Machill K, Schumacher D, Schulzki I, Werner D. Early achievement of mild therapeutic hypothermia and the neurologic outcome
after cardiac arrest. Int J Cardiol. 2009 Apr 3;133(2):223-8
Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ,
Kelly AM, Silvester W; Rapid Infusion of Cold Hartmanns (RICH)

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Investigators. Induction of therapeutic hypothermia by paramedics
after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial. Circulation. 2010 Aug 17;
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10. Diao M, Huang F, Guan J, Zhang Z, Xiao Y, Shan Y, Lin Z, Ding L.
Prehospital therapeutic hypothermia after cardiac arrest: a systematic
review and meta-analysis of randomized controlled trials. Resuscitation. 2013 Aug;84(8):1021-8
11. Kim F, Nichol G, Maynard C, Hallstrom A, Kudenchuk PJ, Rea T, Copass MK, Carlbom D, Deem S, Longstreth WT Jr, Olsufka M, Cobb
LA. Effect of prehospital induction of mild hypothermia on survival
and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA. 2014 Jan 1;311(1):45-52.
12. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager
C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P,
Wanscher M, Wise MP, neman A, Al-Subaie N, Boesgaard S, BroJeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kber L, Langrgen J, Lilja G, Mller JE, Rundgren M,
Rylander C, Smid O, Werer C, Winkel P, Friberg H; TTM Trial Investigators. Targeted temperature management at 33C versus 36C after
cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206.
REVIEWS
Cardiac dysfunction of antineoplastic agents in breast cancer

patients
Anca-Maria Popar-Voica1,2, Andreea Clin1,2, Bogdan Alexandru Popescu1,2, Ana Maria Mitric3,
Rodica Anghel1,3, Ruxandra Jurcu1,2, Carmen Ginghin1,2
Abstract:
Cancer TherapeuticsRelated Cardiac Dysfunction (CTRCD) has become one of the main causes of morbidity and
mortality in cancer survivors. If CTRCD is detected early, prompt administration of cardioprotective treatment may slow the
progression of left ventricular (LV) dysfunction and improve the prognosis. Thus, the management of patients with CTRCD
should focus on early detection and prompt treatment. LV ejection fraction (EF) assessment by 2D TTE has a low sensitivity
in detecting CTRCD at an early stage. There is much interest in the use of myocardial deformation parameters measured by
tissue Doppler imaging or speckle tracking echocardiography to identify early myocardial injury and to anticipate ventricular
dysfunction in patients receiving chemotherapy. Peak systolic global longitudinal strain (GLS) could be the most consistent
parameter that correlates with the subsequent development of CTRCD. Serial monitoring of GLS seems the ideal strategy for
the detection of subclinical LV dysfunction. A relative percentage reduction in GLS of >15% is very likely to be abnormal,
whereas a change of <8% appears not to be of clinical significance. Determining the significance of these changes will require
long-term follow-up. To better understand what defines CTRCD, more research and larger studies are needed and also a dynamic partnership between oncologists and cardiologists.
Keywords: Cancer TherapeuticsRelated Cardiac Dysfunction, myocardial deformation parameters, speckle tracking echocardiography, peak systolic global longitudinal strain, early detection, early myocardial injury, anthracyclines, trastuzumab
Rezumat: Disfuncia cardiac indus de terapia antitumoral (CTRCD) reprezint una din cele mai frecvente cauze de morbiditate i mortalitate n rndul supravieuitorilor unei neoplazii. Dac CTRCD este diagnosticat precoce, administrarea
prompt a medicaiei cardioprotectoare poate ncetini progresia disfunciei cardiace cu ameliorarea prognosticului. Managementul pacienilor oncologici cu risc de CTRCD ar trebui aadar bazat pe diagnosticarea i tratarea precoce a CTRCD. Fracia
de ejecie a ventriculului stng (FEVS) evaluat prin ETT 2D are o sensibilitate redus n depistarea precoce a CTRCD. Exist
un interes deosebit n utilizarea parametrilor de deformare miocardic, msurai prin metodele de Doppler tisular sau speckle
tracking, n identificarea precoce a injuriei miocardice induse de chimioterapie i n prezicerea instalrii disfunciei cardiace.
Strainul global longitudinal (SGL) pare s fie cel mai consistent parametru n acest sens i monitorizarea seriat a SGL poate
reprezenta strategia ideal pentru depistarea precoce a disfunciei subclinice de VS. O reducere procentual relativ a SGL
>15% este foarte probabil s fie anormal, n timp ce o reducere <8% pare s nu aib semnificaie clinic. Semnificaia acestor
modificri necesit urmrire pe termen lung. Pentru a nelege mai bine CTRCD sunt necesare ample eforturi de cercetare
precum i dezvoltarea unei colaborri dinamice ntre cardiologi i oncologi.
Cuvinte cheie: disfuncia cardiac indus de terapia antitumoral, parametrii de deformare miocardic, ecocardiografie
speckle tracking, strain global longitudinal, depistare precoce, injurie miocardic precoce, antracicline, trastuzumab
INTRODUCTION
Breast cancer treatment has made significant advances in recent years1. The use of classic chemotherapy
agents, such as anthracyclines, in combination with
newer targeted agents, such as monoclonal antibodies,
University of Medicine and Pharmacy Carol Davila, Bucharest

Institute of Emergency for Cardiovascular Diseases Prof. Dr. C.C. Iliescu, Bucharest
3
Institute of Oncology Prof. Dr. Al. Trestioreanu, Bucharest
2
has contributed to the increase of overall survival in

breast cancer patients2,3. Unfortunately, the cardiovascular side effects of the antineoplastic agents4,5 have
made cardiac toxicity induced by chemotherapy to become one of the main causes of morbidity and morta-
Contact address:
Anca-Maria Popar-Voica, MD, PhD student
University of Medicine and Pharmacy Carol Davila, Bucharest
Institute of Emergency for Cardiovascular Diseases Prof. Dr. C.C. Iliescu,
Bucharest
Sos. Fundeni 258, sector 2, 022328, Bucharest, Romania
Phone/Fax: +4021 3175227
e-mail: poparaanca@yahoo.com
Anca-Maria Popara-Voica et al.

lity in breast cancer survivors6. In patients with symptomatic heart failure (HF) from cancer treatment, the
mortality rate has been reported to be as high as 60% at
two years7,8. Therefore, cardiotoxicity induced by cancer therapy has become a matter of great concern and
the subject of many research efforts.
Cardiac toxicity induced by chemotherapy includes a
broad spectrum of manifestations that range from cardiac dysfunction and HF to arterial hypertension, myocardial ischemia, thromboembolic events, arrhythmia
and QT interval prolongation. This is why the National
Cancer Institute refers to cardiotoxicity caused by antineoplastic agents in a general manner, as toxicity that
affects the heart9. However, the term cardiotoxicity is
usually used in reference to cardiac dysfunction and
symptomatic HF, which are the most severe and best
studied cardiac side effects of chemotherapy. An Expert
Consensus Statement, endorsed by the American Society of Echocardiography and the European Association
of Cardiovascular Imaging, was recently published and
a more precise term, Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD) was introduced10, cardiotoxicity remaining a broader term.
Definition of CTRCD
Since the early 60s, when cardiac dysfunction induced
by anthracyclines was first reported, several definitions
have been proposed, but a consensus definition lacked
for many years11. Back then, the diagnosis was based
on the presence of signs and symptoms of HF or the
evidence of ultrastructural abnormalities on endomyocardial biopsies. Later, left ventricular ejection fraction
(LVEF) became the most used parameter for the diagnosis of cardiac dysfunction but with no clear cutoff
values, which generated many difficulties with respect
to diagnosis, monitoring and treatment-related decisions. The recently published Expert Consensus Statement finally provides a standardised definition of cardiac
dysfunction induced by chemotherapy10. Cancer therapeutics-related cardiac dysfunction (CTRCD) is defined as a decrease in the left ventricular ejection fraction of >10%, to a value <53% (considered the normal
reference value for two-dimensional echocardiography
(2DE))10. This decrease in LVEF has to be confirmed
by a reevaluation after 2-3 weeks since the first examination10. The document mentions that the reduction in
LVEF can be symptomatic or asymptomatic. It also defines clear cutoff values for the concept of reversibility
and classifies CTRCD accordingly10:
Reversible: improvement in LVEF to within 5% of
the baseline value10

Vol. 24, No. 4, 2014
Partially reversible: improvement in LVEF by

10% from the lowest value but remaining >5%
below the baseline value10
Irreversible: improvement in LVEF by <10% from
the lowest value and remaining >5% below the baseline value10
Indeterminate: re-evaluation of patient not possible10.
Types of CTRCD
Amongst the various antineoplastic agents with potential cardiac toxicity, anthracyclines (including doxorubicin, epirubicin and idarubicin) and trastuzumab,
have been most commonly implicated and best studied
in breast cancer patients. The combined therapy, using
agents from both these classes, generally increases the
incidence of CTRCD12-14.
Based on their potential to cause irreversible versus
reversible damage to the cardiovascular system, Ewer et
al. have proposed a classification of anticancer agents,
with anthracyclines being classified as type I and trastuzumab as type II15. This classification has extended
into distinguishing two different types of cardiotoxicity16 in the larger acception of the term, and, by default, two types of CTRCD10.
Type I cardiotoxicity is related to the classic chemotherapy agents (anthracyclines, mitoxantrone, alkylating agents, antimicrotubule agents, antimetabolites) and has as prototype the toxicity induced by anthracyclines16-18. Type I chemotherapy agents are, usually,
cytotoxic, inducing cell loss (necrosis/apoptosis) which
leads to progressive and largely irreversible cardiovascular damage associated with increased rates of cardiovascular mortality16-18. It was shown that these agents
induce ultrastructural damage (vacuoles, myofibrillar
disarray and dropout, necrosis) on endomyocardial
biopsies and also release of myocardial injury markers
(troponins), as consequence of myocyte damage and
loss8,10,16,19. Moreover, there is a definite relation between the cumulative dose of anthracyclines and the incidence of cardiac dysfunction, as described first by Von
Hoff et al.8 and later, providing more accurate data, by
Swain et al.20.
Conversely, type II cardiotoxicity is related to the
newer targeted agents (anti-HER2, angiogenesis inhibitors, BCR-ABL inhibitors) and has as prototype the
toxicity induced by trastuzumab16-18. Type II agents
are cytostatic and do not induce cell loss, but cellular dysfunction (mitochondrial/protein dysfunction)
which leads to temporary and largely reversible cardiac dysfunction, not associated with increased car-

Vol. 24, No. 4, 2014
diovascular mortality16-18. There is no dose-dependent

relation. Also, no apparent ultrastructural changes on
endomyocardial biopsies have been described, though
not thoroughly studied10.
This classification, however, has limitations. In patients with type I cardiotoxicity, clinical experience has
shown that early detection of cardiac dysfunction and
early administration of cardioprotective medications
may improve LV systolic function19. In addition, trastuzumab, a type II drug, can trigger irreversible cardiac damage in patients with severe preexisting cardiac
disease or it may potentiate the anthracycline type
I CTRCD13. Moreover, as most of the newer targeted
agents were introduced in oncology in the last two decades, their lack of long-term cardiac toxicity needs to
be confirmed in the following years.
Anthracycline-induced type I CTRCD
Based on the time of onset and the duration of symptoms, anthracycline-induced cardiac toxicity has been
categorized into acute, early-onset and late-onset chronic progressive13. Acute cardiotoxic events are relatively
rare (<1% of patients), dose-independent and are, usually, observed from the beginning of treatment and up
to 14 days after it ends13,17. With few exceptions, they are
transient, usually resolving within one to two weeks13,17.
They comprise sudden ventricular repolarization alterations, changes in QT interval, ventricular and supraventricular arrhythmias, acute coronary syndromes,
pericarditis and myocarditis3,21,22. Chronic CTRCD is
dose-dependent, and more prevalent than the acute
form: 1.6-5% of symptomatic HF patients during longterm follow-up 13 and up to 40% of asymptomatic patients with LV dysfunction3,17,21. It may occur either in
the first year after completion of chemotherapy (early
onset, 1.6% to 2.1%) or beyond the first year (late/delayed-onset, 1.6% to 5%)3,13,17,21,22. Reports show that up
to 10-20 years may pass until late-onset CTRCD becomes clinically evident13. Both forms of chronic CTRCD
typically present as dilated cardiomyopathy, which can
be progressive. However, this classification was made
in the early 1990s and is based on retrospective, small
studies in childhood cancer survivors populations13. At
present, there are no available prospective studies on
long-term cardiac effects of anthracycline chemotherapy on adult populations13. Thus, the incidence and
the timing of occurrence of anthracycline-induced
CTRCD are not well defined13.
Genetic predisposition and other various risk factors (Table 1) influence the progression and degree of
anthracycline-induced CTRCD. Among them, the to-

Table 1. Risk factors associated with anthracycline-induced

CTRCD
Younger/ older age
Female gender
Rapid intravenous injection
Cumulative dose exceeding:
Daunorubicin 550-800 mg/m2
Doxorubicin 400-550 mg/m2
Epirubicin 900-1000 mg/m2
Idarubicin 150-225 mg/m2
Early mediastinal radiation, or concomitant doxorubicin exceeding a
cumulative dose of 450 mg/m2
Hypertension, coronary artery disease
Electrolyte disturbances: hypocalcemia, hypomagnesemia
Genetic predisposition
Adapted from 21.
tal cumulative dose of anthracyclines is the most important13,21,23. The recommended maximum lifetime
cumulative dose for doxorubicin is 400-550 mg/m2 but
it seems that there is no completely safe dose13,24. Studies evaluating doxorubicin-induced CTRCD reported
rates of 3-5% with 400 mg/m2, 7-26% at 550 mg/m2
and 18-48% at 700 mg/m2 8,20. Dose-limiting strategies
reduce CTRCD. In breast cancer patients the currently
doses of doxorubicin, used in combination with modern adjuvant therapy, are between 240 and 360 mg/
m2 and are associated with a incidence of HF around
2%20. However, microscopic analysis shows myocardial
damage even with doses of doxorubicin as low as 180
mg/m2 25. All risk factors are related to chronic CTRCD
but not with the acute forms21,26,27.
The exact pathophysiological mechanism for anthracycline-induced CTRCD is still not clearly defined.
It is known that topoisomerase 2 (Top2) represents the
molecular target of anthracyclines28,29. Top2 is essential
in modulating deoxyribonucleic acid (DNA) structure during transcription; replication and recombination28,30. It has been shown that humans express two
Top2 isoenzymes, namely Top2 and Top 228,31. Top2
is expressed in rapidly proliferating cells, such as the
malignant cells, and it represents the primary target of
the anticancer activity of the anthracyclines28. On the
other hand, Top2 is expressed in quiescent cells and
is the only Top2 isoenzyme expressed in the heart tissue28,32. Recent studies indicate that the Top2 isoenzyme is probably the target for the cardiac toxicity induced by anthracyclines28. In the heart tissue, anthracyclines bind to Top2, with the formation of ternary
complexes (Top2 anthracyclineDNA)10,28. These
complexes lead to DNA double-stranded breaks and
transcriptome changes which, in turn, activate the apo

ptotic pathway and also selectively affect oxidative phosphorylation, mitochondrial biogenesis, and the p53
pathway10,28. Through these main pathways: induction
of cell apoptosis, reduction of adenosine triphosphate
production from the mitochondria, and generation of
reactive oxygen species, anthracyclines induce injury
of cardiomyocytes28. The injury of myocytes progresses
(myofibrillar disarray, necrosis and cell loss) with the
increase of the cumulative dose of anthracyclines and
finally leads to the death of cardiomyocytes28. The consequence is represented by a progressive decrease in
the number of cardiomyocytes, leading to ventricular
remodeling21,33. Studies using endomyocardial biopsy
and troponin I measurements showed that cardiomyocyte injury may occur during or early after anthracycline exposure8,16,19. However, due to cardiac reserves and
the activation of compensatory mechanisms, the clinical manifestations may become apparent after months
to years from the initial exposure to anthracyclines16.
Trastuzumab - induced type II CTRCD
Trastuzumab, a recombinant humanized monoclonal
antibody, is used for the treatment of HER2-positive
breast cancer patients. The HER2 gene is expressed in
25-30% of breast tumors and determines an overproduction of human epidermal growth factor receptor 2
(HER2)13. These tumors are considered very aggressive and have a worse prognosis13. The introduction of
trastuzumab in the treatment of HER2-positive breast
cancer has determined a 50% reduction in recurrence
and a 33% increase in survival13,14,34.
The HER2 receptor is also expressed by the heart tissue and studies have shown that it plays an important
role in the normal growth, repair and survival of cardiomyocytes35,36. Trastuzumab binds to the extracellular
domain of HER2 and inhibits its signal transduction,
thus, directly inhibiting the antiapoptotic signaling
pathways and making cardiac dysfunction possible21.
As previously described, cardiac dysfunction induced
by trastuzumab has a better prognosis than that caused
by anthracyclines, as it often occurs during treatment,
is reversible in most cases and it is not associated with
ultrastructural lesions on endomyocardial biopsy18,43.
Also, trastuzumab rechallange after recovery of cardiac
function is, usually, safe18.
The data from the pivotal and adjuvant trials on trastuzumab point out to the existence of an important anthracycline trastuzumab interaction. It was observed
that the most important risk factor for trastuzumab induced CTRCD is the association with high cumulative
doses of anthracyclines (>300 mg/m2)21. It also seems

Vol. 24, No. 4, 2014
that trastuzumab potentiates anthracyclines toxicity

especially when the two drugs are given concurrently,
or when the time interval between the administration
of the two regimens is short. In the pivotal metastatic
HER-2 positive clinical trial, in which trastuzumab
was administered concurrently with anthracyclines,
the incidence of cardiac toxicity was very high, cardiac
dysfunction being reported in 27% of cases and NYHA
III/IV HF in 16% of cases37,38. By contrast, in the adjuvant trastuzumab trials, in which trastuzumab and
anthracyclines were given in a sequential manner, the
reported incidence of cardiac dysfunction ranged from
3-18.1% and of NYHA class IIIIV HF from 0-3.9%37,38.
Among the adjuvant trials, the HERA trial, in which
the time interval between the administration of the two
regimens was the longest, reported the lowest incidence of HF37,38. Furthermore, when trastuzumab was given to patients who did not receive anthracyclines, the
incidence of cardiac toxicity was even lower, such as in
the third arm of the BCIRG 006 trial in which the incidence of cardiac dysfunction was of 8.6% and of NYHA
class IIIIV HF of 0.38%39.
There are some relevant aspects that may explain this
anthracyclinetrastuzumab interaction18. Trastuzumab
is, usually, administered to patients who have already
been exposed to anthracyclines, and whose heart tissue is, thus, vulnerable in response to the injury induced by anthracyclines18. It seems that following anthracyclines administration there is a HER 2 overexpression in the vulnerable myocardium, by which cell
repair mechanisms are activated40-42. If trastuzumab is
given during a time interval in which the myocardium
is vulnerable, it will block the HER2 related cell repair and survival mechanisms and will potentiate and
augment the injury induced by anthracyclines18. This is
probably why, in some patients with a history of recent
exposure to anthracyclines, trastuzumab may promote
an irreversible cardiac dysfunction18.
Other risk factors for trastuzumab induced CTRCD
are pre-existing LV dysfunction or systemic arterial
hypertension, a body mass index >25 and advanced
age13,21. Chest radiotherapy associated with trastuzumab seems to be clinically safe21,34. Recent evidence
shows a higher incidence of trastuzumab-related cardiotoxic effects in cancer patients aged over 70, with a
history of heart disease and/or diabetes21,44.
Early detection of CTRCD using echocardiography
It has been shown that symptoms of CTRCD often become clinically apparent only after irreversible myocardial damage has occurred10. Also, if diagnosed late in

Vol. 24, No. 4, 2014
its course, HF due to CTRCD is often resistant to therapy10. By contrast, if CTRCD is detected early, prompt
administration of HF treatments may slow the progression of LV dysfunction or prevent the development of
late CTRCD3. Moreover, anticancer drug combinations
could be modified as to reduce further cardiac damage3. Thus, the management of patients with CTRCD
should focus on early detection and prompt treatment.
So far, early detection of CTRCD was mainly based
on serial cardiac imaging to identify asymptomatic reductions in LVEF. Two-dimensional (2D) transthoracic
echocardiography (TTE) is the most commonly used
method in this setting. However, LVEF assessment by
2D TTE has a low sensitivity in detecting CTRCD at an
early stage, due to some significant limitations: it presents technique-related variability45; it reflects global
function and it does not detect subtle regional changes10,22,46; it may be affected by changes in loading conditions10; and also, the reduction in LVEF is often a late
phenomenon, occurring only after a critical amount of
myocardial damage has taken place19,45,47-50.
Growing attention is being paid in defining markers of early myocardial changes that can predict subsequent LVEF reduction or the progression to HF. This
would allow the early identification of patients at high
risk for developing significant LV dysfunction and the
initiation of prevention strategies by using targeted
monitoring, as well as the possibility, to introduce cardio-protective medications45.
There is much interest in the use of myocardial deformation parameters measured by tissue Doppler
imaging (TDI) or speckle tracking echocardiography
(STE) to identify early myocardial injury and to anticipate ventricular dysfunction in patients receiving chemotherapy45,51. The advantages of these parameters include the possibility to detect regional abnormalities in
LV function, their improved reproducibility and their
reported ability to predict subsequent LV dysfunction10,45.
It has been shown that the reduction of myocardial deformation parameters is an early sign of subclinical myocardial damage induced by chemotherapy,
and occurs before any reduction in LVEF as assessed
by conventional 2D TTE10,13,22,45,51,52. It has also been
reported that reductions of myocardial deformation
parameters correlate with subsequent LVEF reduction or the development of HF, which represents the
real value of these parameters10. Earlier studies focused
on TDI-based strain parameters, among which interventricular septal peak systolic longitudinal strain rate

was reported to be the most consistent in detecting

the early myocardial changes during chemotherapy45.
Recent studies use 2D STE to measure different myocardial deformation parameters (strain, strain-rate and
twist). Among them peak systolic global longitudinal
strain (GLS) is significantly related to the subsequent
development of CTRCD10,45. Because of baseline variability in strain values between different patients, it has
been shown that the within-patient change of STE-GLS
is a more reliable parameter compared to a populationderived absolute cut-off value10,45,54. Although the cutoff value for within-patient change in STE-GLS that
predicts CTRCD is not clear, it has been reported that
values between 11-15% appear to have the best specificity10,45,54. In patients where a relative change in GLS is
unavailable, absolute levels of GLS > -19% and -20.5%,
early during chemotherapy, have been associated with
CTRCD45,53,54. In contrast, neither global radial strain
nor global circumferential strain proved consistently
predictive of CTRCD45,53,54.
The recently published Expert Consensus Statement recommends the serial monitoring of GLS as the
ideal strategy for the detection of subclinical LV dysfunction10. GLS assessed during chemotherapy should
be compared with the one measured at baseline, and
the within-patient change in STE-GLS should be noted10. The authors mention that the relative percentage
reduction in GLS of >15% is very likely to be abnormal,
whereas a change of <8% appears not to be of clinical
significance10. Also, it is recommended to confirm the
abnormal value of GLS by a repeat study that should be
performed two to three weeks after the initial abnormal
study10.
CONCLUSION
Advances in breast cancer treatment and the subsequent increase in disease-free survival have led to an
increase of cardiac complications induced by cancer
therapy. As overt HF induced by chemotherapy has
such a worse prognosis, there is a stringent need to improve our ability to detect CTRCD at a subclinical level.
Echocardiography has a major role in this setting, with
evidence supporting the use of myocardial deformation
parameters measured by 2D-STE in detecting the subclinical CTRCD. Among them, STE-GLS seems to be
the most consistent parameter that correlates with the
subsequent development of CTRCD. The serial monitoring of STE-GLS has been included in the assessment
and monitoring of cardiac function in cancer patients
as the ideal strategy for the detection of subclinical LV

dysfunction. Determining the significance of these

changes will require long-term follow-up before GLS
may be used in treatment related-decisions. To better
understand what defines CTRCD, more research and
larger studies are needed and also a dynamic partnership between oncologists and cardiologists.
Acknowledgement: This paper is supported by the Sectorial Operational Programme Human Resources Developement (SOP HRD), financed from the European
Social Fund and by the Romanian Government under
the contract number POSDRU/159/1.5/S/137390.
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Independent and incremental value of deformation indices for prediction of trastuzumab-induced cardiotoxicity. J Am Soc Echocardiogr 2013;26:493-8.
REVIEWS
Utility and prognostic value of exercise stress testing in post

revascularization patients
Daniel Gherasim1, Bianca Moise2, Eduard Apetrei1,3
Abstract:
Exercise testing (ET) is a well-established, safe an cost-effectiveness procedure which is widely used in clinical
practice for many decades for detection of coronary artery disease (CAD). The mean test sensitivity and specificity are not
very high and are lower than the values for the most expensive imaging procedures mentioned in the current guidelines for
stable CAD. Modern ET is not limited to the observation of ST segments abnormalities, important information can be obtained from exercise capacity, which is the most important predictor of mortality, heart rate and blood pressure response and/or
development of arrhythmias , during the exercise, but also in the recovery period. Some prognostic scores including ET variables were developed for increase the predictive value of ET. Worldwide, the decrease in cardiovascular mortality was possible
through a better management of risk factors, but also through development of new revascularization therapies, devices and
antiischaemic agents. Restenosis continue to be the major limitation of coronary revascularization and patients after coronary
revascularization could be identified as being at high risk for future cardiac events. New generations of stents with lower rate
of restenosis are developed and the trend of research in this field is a dynamic one. There are only few studies examining the
utility of exercise testing after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG).
There is no consensus regarding the use of exercise testing after PCI or (CABG). There are divergent opinions regarding the use
of ET post PCI as a routine strategies or functional (symptom-driven) strategies. Angina post-PCI is an insensitive marker of
restenosis, as between 25% to 50% of patients have cardiac ischemia that is clinically silent. Recurence of symptoms may occur
in 10 to 20 percent of patients after stent implantation; the rate for stent restenosis is 30-40% following balloon angioplasty
and 20-30% after stenting with bare metal stents, and <10% with drug-eluting stents. For better evaluation of the risk of restenosis and/or progression of native CAD, less commonly used ECG criteria could be useful in the exercise electrocardiography
(ECG) changes analysis. To summarize, exercise testing is very useful in the detection of ischemia in postrevascularization
patients, despite some inherent limitations which alter also the accuracy of the test for the initial evaluation of suspected CAD.
The post-revascularization patients are high risk patients who need to be carefully evaluated early, but also late after the revascularization procedure and the ET, especially in centers with a good expertise, is the first option in noninvasive evaluation of
this growing group of patients.
Keywords: exercise stress testing, predictive value, percutaneous coronary interventions (PCI), coronary artery bypass graft
surgery (CABG).
Rezumat: Testul de efort reprezint o metod util, sigur i cu un bun raport cost/eficien, fiind utilizat de mult timp i pe
scar larg n practica clinic pentru diagnosticul bolii ischemice coronariene. Sensibilitatea i specificitatea testului de efort
nu sunt foarte nalte, dac ar fi s le comparm cu sensibilitatea i specificitatea raportate pentru tehnicile imagistice, mai
scumpe, aa cum sunt trecute n ghidurile curente. n prezent, interpretarea testului de efort nu se limiteaz doar la modificrile segmentului ST, ci i la alte date cum ar fi capacitatea de efort, cel mai important predictor de mortalitate, rspunsul
frecvenei cardiace i a tensiunii arteriale, ca i prezena aritmiilor, att n faza de exerciiu propriu-zis, ct i n faza de recuperare sau revenire. De asemenea, au fost dezvoltate scoruri de risc pe baza datelor obinute la testarea de efort, tocmai pentru
creterea valorii predictive a testului. Scderea, la nivel global, a mortalitii prin boli cardiovasculare a fost posibil printr-un
mai bun control i tratament al factorilor de risc, dar i prin dezvoltarea unor noi tehnici de revascularizare i a medicaiei
antiischemice. Restenoza rmne principala limitare pentru orice modalitate de revascularizare, pacienii coronarieni, postrevascularizaie, putnd fi ncadrai ca avnd un risc crescut pentru evenimente cardiace. Au aprut noi generaii de stenturi cu
rate sczute pentru restenoz i cercetrile n acest domeniu continu. Au fost publicate puine studii care evalueaz utilitatea
testului de efort dup revascularizaie, fie ea intervenional sau chirurgical i nici nu exist un consens privind testul de
efort la pacieni dup revascularizare. Opiniile sunt mprite privind efectuarea testului de efort, de rutin sau doar n cazul
Prof.Dr.C.C.Iliescu Emergency Institute for Cardiovascular Disease,

Bucharest
2
Sanador Hospital, Bucharest
3
Carol Davila University of Medicine and Pharmacy, Cardiology Department, Bucharest
Contact address:
Dr. Daniel Gherasim, Clinical Cardiology, Prof. Dr. C.C. Iliescu Emergency Institute for Cardiovascular Disease, Bucharest, Sos. Fundeni 258,
Sector 2, Bucharest, Zip code 022328
E-mail: gherasimdanro@yahoo.com

Vol. 24, No. 4, 2014

Utility and prognostic value of exercise stress testing
apariiei simptomelor. Trebuie spus c angina nu poate reprezenta un marker sensibil pentru restenoz, din moment ce n 25
pn la 50 % din cazuri, ischemia este silenioas. Recurena simptomelor poate apare n 10-20% din cazuri dup stentare,
iar rata restenozei este apreciat la 30-40% dup angioplastie cu balon, la 20-30% dup stent metalic i la <10% din cazuri
dup stent activ. Pentru o mai bun evaluare a riscului de restenoz sau/i progresia bolii ischemice, au fost analizate criterii
electrocardiografice (ECG) mai puin utilizate i care ar putea fi utile n interpretarea modificrilor ECG. n concluzie, testul
de efort este deosebit de util n depistarea ischemiei, n ciuda limitrilor cunoscute i care influeneaz acurateea testului i
atunci cnd l folosim ca evaluare iniial, n scop diagnostic. Pacienii dup revascularizare sunt pacieni la risc nalt i trebuie
atent monitorizai, att precoce, dar i la distan dup efectuarea procedurii, testul de efort fiind prima opiune n evaluarea
noninvaziv a acestor pacieni, mai ales n centrele cu o bun experien n domeniul testrii de efort.
Cuvinte cheie: test de efort, valoare predictiv, angioplastie, revascularizaie chirurgical.
INTRODUCTION
Cardiovascular diseases (CVD) remains the main cause of death, accounting for 4 million deaths per year
in Europe or 40% of all deaths in EU countries1,2. Coronary heart disease only, accounts for almost 1.8 milion deaths, or 20% of all deaths in Europe annually,
with Baltic countries and central and eastern European
countries having the highest mortality rates. Mortality
rates for ischemic heart disease are higher for men then
for women in all countries, with 70% on average higher in men in EU member states. In our country the
IHD mortality rates per 100 000 population were 287
for women and 425 for men (Source: 2011.Eurostat Statistics Database)2.The economic implications are huge
for the health care budget and for that, identification of
patients at high risk of adverse events is crucial.
The exercise stress test is used in the evaluation of
symptomatic patients to predict the presence and extent of coronary artery disease (CAD) and remains,
despite a not very high sensitivity reported in old studies, the most widely accessible and relatively inexpensive method for initial evaluation of suspected coronary
artery disease. From a meta-analysis of 147 studies, the
standard exercise electrocardiographic cut-point of 0,1
mV of horizontal or down sloping ST segment depression selected as discriminating cut-point for ischemia,
has a mean sensitivity of 68% and a mean specificity of
77% for the detection of CAD. In a retrospective case
series of 404 patients from our center, we found a higher predictive value for exercise testing; the sensitivity
of the test was 85.3% and the specificity 46.8%, the positive predictive value was 65.3% and the negative predictive value was 73.1% (paper under press).
Dynamic changes in the prevalence and treatment of
cardiovascular risk factors in the modern era or in the
treatment of stable coronary artery disease or acute coronary syndromes have produced changes in the prevalence of CAD and CVD mortality and also changes in
the inducible ischemia during stress tests3.
The ECG exercise test (ET) has a class I indication

for the diagnosis of obstructive CAD, but the predictive value of ET post coronary revascularization is still a
issue for debating4.
In the last decades, some controversial ECG criteria
have been analyzed in the attempt to increase the sensitivity of the test: heart adjustment of ST depression,
P wave prolongation, U wave changes, transient axis
shifts or duration or amplitudes of QRS complex, QT
interval and T-wave subintervals. An important issue,
beside the identification of obstructive disease, is the
prediction of future coronary events and mortality by
the ET. Methods demonstrated the prognostic value
include evaluation of exercise capacity, which is considered the most important prognostic marker obtained
by exercise test, chronotopic competence and incompetence, peak exercise blood pressure response, heart
rate recovery and frequent ventricular ectopy during
recovery, and also exercise test scores, which incorporate clinical and demographic risk factors4-6.
A. Exercise testing after PCI
The use of percutaneous coronary interventions (PCI)
for treatment of CAD has dramatically increase in the
last three decades. The first coronary artery bypass
grafting (CABG) was performed 50 years ago, in 1964,
in the same period when the first report of one of the
most used test in clinical cardiology, the Bruce protocol
exercise treadmill test, was published7,8. Thirteen years
later the first PCI was performed, becoming during
the last decades, one of the most frequently performed
therapeutic interventions in medicine. In 1993 the first
bare-metal coronary stent was developed and approved for the USA market, and in 2002 the drug-eluting
stents (DES) were approved for the European market.
Nowadays the stents are currently used in >80% of PCI
procedures and the trend of researches for better quality devices is a very dynamic one.
There are three major questions to be solved regarding the ET post PCI: 1) the optimal period to perform


Vol. 24, No. 4, 2014
the ET (the timing of ET); 2) the value of ECG and hemodynamic responses; 3) the predictive value for different strategies of revascularization.
1. When we will perform an exercise test after revascularisation?
Restenosis remain a major and probable single limitation of PCI and reflect complex pathophysiology
processes. Clinical events after balloon percutaneous
transluminal coronary angioplasty (PTCA) are attributable to arterial renarrowing at the PTCA site, intimal
hyperplasia in the area of coronary stenting, progression of atherosclerotic disease at remote sites, or a combination of these events. Angiographic and clinical restenosis are generally developing within 6 to 9 months
after PTCA and major cardiac events, including death
or myocardial infarction, and progression of atherosclerosis occurring as a low, but constant risk (1-2%
risk per year) indefinitely after the procedure. The risk
of restenosis after PTCA depends on clinical factors,
such as diabetes mellitus or prior restenosis, anatomical factors such as total oclusions or smaller vessel size,
and procedural factors, such as the final minimal lumen diameter.
The accuracy of ET for detection of restenosis, as for
the diagnosis of CAD, depends of the moment when
the test will be applied in the continuum of cardiovascular disease, as shown in Figure 1.
Recurrence of symptoms may occur in 10 to 20 percent of patients after stent implantation; the rate for
stent restenosis is 30-40% following balloon angioplasty and 20-30% after stenting with bare metal stents, and
<10% with drug-eluting stents, but recurrent rates were
reported in some studies being even higher, up to 80%.
depending on vessel size or type of restenosis. (intrastent, marginal, remote disease9.
Figure 1. The accuracy value of exercise testing is correlated with the severity
of CAD and the moment when we apply the test in continuum of coronary
artery disease. The cut-point used for abnormal ST-depresion could coincide with the apearence of significant stenosis. Earlier we performe the test,
better will be the prognosis, either for suspected CAD or for already knew
CAD. ET=exercise testing; CA=coronary angiography. ET1 and ET 1a=tests
performed in a moment when the lesions are minimal; ET 2 and ET 2a=tests
performed when the lesions are clinical and/or hemodynamic significants.
ET, stress echocardiography and nuclear imaging had

a better sensitivity (63% and 87%, respectively) and
specificity (87%, and 78%, respectively), but the studies
which were analysed were published between 1975 and
200011. A lot of changes in the paterns of risk factors,
and therapies occurred since than. There are only few
data about the predictive value of ET nowdays.
The ET for the detection of restenosis or new lesion
has a sensitivity of 61%, specificity of 63%, a PPV of
67%, and a NPV of 57%, in a study on 66 males who
had performed an ET before and 6 months after procedure12.
2. The ET is still using in the modern era of cardiology ?

Despite a modest reduction in stress testing rates after PCI from 59.3 per 100 person-year in 2006 to 47.1
per 100 person-year in 2008, the rate of ECG ET post
PTCA compared with exercise test with imaging increased slighty over time, an increase which is significant
after adjustement10.
3. Sensitivity of ET for the prediction of restenosis
A meta-analysis showed that ET has a poor sensitivity (46%) and a moderate specificity (77%), for the
identification of post-PCI restenosis. Comparing with
Figure 2. Routine exercise testing in a 62 year old female with diabetes and
dyslipidemia, 3 months after balloon percutaneous transluminal coronary
angioplasty (PTCA) and bare metal stent (BMS) implantation on proximal
LAD, revealed silent ischemia (important downsloping ST depression in
leads II, III, aVF, V3-V6 and ST elevation in aVR, ST abnormalities which
had persisted 10 minutes in recovery period) due to restenosis, angiographicaly confirmed.

Vol. 24, No. 4, 2014
4. Routine versus functional strategies

It is unclear if a routine early ET strategy is predictive
of clinical events or not. There are few studies in which
the conclusions favor the early post PCI strategy, but
the majority of observational studies does not support
the role of ET early after PCI.
Angina post-PCI is an insensitive marker of restenosis, as between 25% to 50% of patients have cardiac
ischemia that is clinically silent13,14. The exercise test
performed in our laboratory of a female patient which
had developed asymptomatic restenosis is presented in
Figure 2.
In a post-hoc analysis of the subgroup of patients
that underwent ET 6 weeks following the PCI (the routine arm) in the ADORE trial (Aggressive Diagnosis of
Restenosis), the authors found that early ET was poorly
predictive of clinical events, with a positive predictive
value of 21.9%. The sensitivity was 41.2%, the specificity was 73,3%, and the negative predictive value was
87.5 %.The ADORE trial compared a strategy of routine functional testing with a selective, symptom driven
strategy, clinical follow-up being at 9 months. The poor
sensitivity could be related to the low probability to find
a significant restenosis prior to 6 weeks following PCI,
and also to the low sensitivity of ET for the detection
of one-vessel disease compared with multi-vessel CAD.
A subgroup of patients with diabetes randomized to
routine FT had a higher composite clinical event rate
than those randomized to the selective strategy, but the
procedural rates did not differ significantly15.
In the second ADORE trial (ADORE II), the same
ET strategies were compared, but this time in high risk
patients: diabetes, multivessel disease, left ventricular
ejection fraction <35%, and/or PCI of the proximal left
anterior descending artery. The quality of live (QOL)
and functional status were assessed also. More positive tests were observed at 6 months compared with 1.5
months evaluation (almost double).The incidences of
cardiac procedures and clinical events were not significantly different at nine-up follow up, but routine
exercise endurance was improved in the routine arm,
without significant improvement of the QOL16.
In the Routine versus Selective Exercise Treadmill Test
after Angioplasty (ROSETTA) Registry, the investigators found that was five-fold difference in the intensity
of functional testing between patients who underwent
the routine and selective testing strategies, in 791 patients from 13 centers in 5 countries. The routine functional testing was not associated with an increase in the
use of cardiac procedures, but was associated with a

reduction in cardiac events, including unstable angina

(6.1% versus 14.4%; p = 0.001), myocardial infarction
(0.4% versus 1.6%; p = NS), death (0% versus 2.2%;
p = 0.02) and composite clinical events (6.3% versus
16.3%) during 6 month follow-up, as shown in Figure
3. The patients enrolled in the routine arm were more
likely to receive two or more anti-anginal medications
(57% versus 43%, respectively; p = 0.0002). The difference clinical events could be attributable to the early
identification and treatment of patients at risk for
follow-up events, the major benefit of routine strategy
being reassurance for patients and physicians. One of
the conclusion was, therefore, that despite a previous
founded low sensitivity and specificity in the post PCI
setting, the routine use of exercise electrocardiography
alone, could improve outcomes17.
5. ECG changes
The exercise test ussualy is performed for the detection of CAD, using an discriminatory cut-point of
Figure 3A. Cardiac procedures during the first 6 months after percutaneous
transluminal coronary angioplasty (PTCA) among patients in the ROSETTA Registry. CABG=coronary artery bypass graft.
Figure 3B. Clinical events during the first 6 months after percutaneous coronary angioplasty among patients in the ROSETTA Registry. The composite endpoint was comprised of unstable angina, myocardial infarction and
death. From ref. 17,with permission from HMP Communications.

0,1 mV of horizontal or downsloping depression, and

without antiischemic therapy, the result being positive, negative, inconclusive or equivocal. Post PCI, when
we already know the CAD is present, the test must be
performed with medication, including, for example,
beta-adrenergic blockade agents, and for this reason
the criteria of submaximal heart rate cant be used for
the definition of test as maximal or submaximal. Revised formulas for determination of age-predicted maximal heart have been proposed, eg. maximal heart rate
= 164-0/72 x age18. The main criteria will be exercise
capacity, estimated from exercise time or measured
during a cardiopulmonary exercise testing. There are
no divergent opinions concerning the cut-off point for
ischemia, which will be the same (0,1 mV), but the ST
depression dont have the same prognostic value in patients with different therapeutic strategies for revascularization. In the DANAMI-2 (the second DANish trial
in AMI) study, the ST depression was more frequent
and was an independent risk predictor in patients treated with fibrilolysis, but not in the PCI group. Exercise
capacity was the most powerful prognostic predictor
for death and re-infarction for every treatment strategy,
an increasing with one metabolic equivalent of the task
(MET) being correlated with a 20% decrease of death
and reinfarction19.
For purpose of early detection of restenosis, we have
looking for another criteria to increase sensitivity of ET,
ST segment changes <0,1 mV being not very uncommon. A number of facts must be taken into account:
resting ECG showing Q waves or intraventricular conduction abnormality, incomplete revascularization, the
relative common ST depression observed predominantly within 2 weeks or even later, without remaining
significant stenosis, especially in patients with diabetes
or hypertension. The ET cant differentiate between restenosis and a new lesion, but the general agreement is
that the main purpose for ET in patients post PCI is the
detection of restenosis.
6. Compare the results of ET before and after PCI
One of the strategy which can help us is to perform
an ET before the PCI and another ET after PCI, and
to compare the ECG territories where ST changes have
occurred. ST-segment changes observed in other leads
after angioplasty compared with the preangioplasty
exercise test may show a false-positive result, during
an ET performed 3 months after angioplasty20. Also, an
increase in exercise capacity after PCI was correlated
with coronary luminal enlargement achieved with angioplasty, and decrease of exercise capacity was correla

Vol. 24, No. 4, 2014
Figure 4. The role of ET in the decision for repeated coronary angiography

in postrevascularization patients.
ted with luminal reduction and restenosis, when the ET

and angiograms obtained 2 weeks before and 20 weeks
after PCI were compared21.
One interesting observation is that the rate of false positive tests in the first month after PCI is higher
in patients with DES implantation, probably due to a
more proeminent endothelial dysfunction, even DES
are associated with a reduced rate of restenosis, compared with bare metal stents22. Concernings were formulated about the plaque instability and the safety of ET in
the first 24-48 hours, beside his utility short after PCI.
A Swiss study showed us that early ET first day after
coronary bare-metal stenting is safe (the number of patients with stent thrombosis was the same in active and
control group) and offer important prognostic information about mortality, trend toward repeat revascularization and risk for major adverse cardiac events, all of
them being at higher level in patients with positive ET,
especially in combination with incomplete revascularization, which was defined as stenosis >50%23.
In a small study (29 patients), Milo M et al.24 have
demonstrated a lower coronary blood flow response
to adenosine assessed by transthoracic Doppler echocardiography in patients with ST segment response
1 mm to exercise in serial ET during a follow-up of 6
months, ST segment changes being related to the presence of coronary microvascular dysfunction (CMVD)
in the above mentioned period. The utility of ET early
(within 2 weeks) only for detection of ischemia is debatable25.
7. Unconventionaly ECG criteria
Not validated criteria for detection of ischemia,
some ECG findings marked as controversial or less
commonly used, seems to have a better sensitivity in
the prediction of restenosis.

Vol. 24, No. 4, 2014
The sum of ST depression (ST index) of leads II,

III, aVF, V4-V6 reported to heart rate index (HR)
was 13.7 in the restenosis group and 9.3 in the patent
group (p=0.017) in a study with patients receiving PCI
to treat acute coronary syndrome (ACS). The sensitivity, specificity, positive predictive value, and negative
predictive value of this index were 85%, 63%, 44%, and
92%26. Also, the increase of ST/HR index from one test
to another, performed in a period from 3 months to
12 months after PCI, showed o very high sensitivity, of
91% and a specificity of 77%, with a positive predictive
value of 70% and negative predictive value of 94%27.
The ST changes in recovery phase in relation to heart
rate, represented as rate-recovery loop, has been found
to be more specific for the identification of restenosis
then ST depression alone. In patients with ischemia,
the loop has an counterclockwise aspect, different from
what we find in normal patients where a clockwise raterecovery loop is recorded6.
Using ST depression, heart rate and rate-recovery
loop, Lehtinin et al.28 developed ST /HR hysteresis which exceed the simplest ST/HR index or ST segment depression for the detection of ischemia, but the method
need to be incorporated in computer-based algorithms.
The addition of right precordial leads V3R through
V5R or the calculation of QRS score were reported to
improve the diagnostic ability of standard exercise testing in detecting silent ischemia due to restenosis, especialy, for right precordial leads, in patients undergoing
PCI in right coronary artery or left circumflex artery29.
The QRS score (or ATHENS Score) combine the amplitude changes in R, S, and Q waves obtained in two leads
and use a cut-off of less than 5 mm.for the detection
of ischemia30: QRS score (mm) = (R- Q-S) avF +
(R- Q-S) V5.
The P wave prolongation or abnormal exercise induced QT dispersion (ie, the difference between the
shortest and the longest QT intervals when multiple
Figure 5. The exercise tests in a case series of 108 patients post revascularization and the follow-up coronary angiography. Ref.35.

leads are compared) have been proved to increase the

sensitivity of the ET for detecting ischemia.
B. Exercise testing after CABG
There is no consensus regarding the use of exercise testing after coronary artery bypass graft surgery (CABG).
In this group of patients, often with rest ECG abnormalities, there is a concern about accuracy of ET. In
asymptomatic patients, the rate for silent graft disease
could be higher with venous conduits. The disappearance of ST depression was associated with a high probability of complete revascularization, but up to 30% of
the patients with complete revascularization continue
to have ST depression. Also, the ST response can be
normal in the presence of occluded graft, if the other
grafts are still opened. The STsegment depression seems to be not as reliable as preoperative ST-segment
depression and must be correlated with the other data
obtained from ET, ie exercise capacity31.
The test provide more useful information some years
later after surgery (5 to 10 years), when the likelihood
of coronary disease is raising.
In a meta-analysis the ET has a sensitivity of 45%
(95% CI 36% to 54%) and a specificity of 82% (95% CI
68% to 95%) for prediction of graft restenosis or progression of native disease. The imaging techniques had
a better sensitivity; a sensitivity of 68% and a specificity
of 84% for stress myocardial perfusion imaging, sensitivity of 86% and specificity of 90% for stress echocardiography were proven32.
In Bypass Angioplasty Revascularization Investigation (BARI) trial, which had compared an initial strategy
of surgical to percutaneous revascularization on mortality and recurrent infarction in patients with multivessel disease, the patients performed an ET at one
year, two years and five years after procedure. There is
no important role for routine ET at least three years
after revascularization, but a good exercise capacity
(achieving the third stage of the Bruce protocol) and
having a Duke risk score > -6 at the test performed fiveyears after CABG, is indicative for a two-years survival
after the test33.
The ACC/AHA Practice Guidelines for Exercise Testing recommend the periodic ET monitoring only for
selected, asymptomatic high risk patients for graft reoclusion as class II b indication, the same as for detection of restenosis, incomplete revascularization, or disease progression.
Another registry which had compared the two strategies, routine vs functional in 408 patients with coronary artery bypass graft surgery (CABG) was The

Routine versus Selective Exercise Treadmill Testing after

Coronary Artery Bypass Graft Surgery (ROSETTA-CABG) Registry. During the 12-month follow up, clinical
events and cardiac catheterizations were less common
among patients who underwent routine functional testing, but the numbers of revascularization procedures
(cardiac catheterizations, PCI, repeat CABG) were the
same. Also, the ET results had not a strong impact on
prescription of anti-anginal dugs. The event rates was
very low and the authors dont warrant the routine
functional strategy after CABG34. In practice the patterns vary widely and the expertise of the center rather
than the clinical characteristics of the patient determines the use of ET.
In a study performed in our center on 108 patients
postrevascularization, the exercise test had found to
have an important role in the decision for repeated angiography (Figure 4).
The ET was positive in more than 70% of cases for
progression pf the disease, graft occlusion, or intrastent
restenosis35 (Figure 5).
To summarize, exercise testing is also a useful tool
in the detection of ischemia in postrevascularization
patients, as in initial evaluation of suspected CAD. A
carefully analysis of the ECG changes and of the other
parameters derived from ET could identify those patients with an increasing risk for restenosis. The test is
safe and with a good cost/quality ratio. The postrevascularization patients are high risk patients who need to
be evaluated early, but also late after the revascularization procedure. The exercise testing, especially in centers
with a good expertise, is the first option in noninvasive
evaluation of this growing group of patients.
Competing interests: The authors declare that they
dont have competing interests.

Vol. 24, No. 4, 2014
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CASE PRESENTATION
Behcet disease: one of the etiologies of myocardial infarction in

young patients
Benhalla Hanane1, Noureddine Malika2, Habbal Rachida3
Abstract:
We report a case of myocardial infarction in the course of Behcets disease in a 25 year old man with no coronary
risk factor. The diagnosis of Behcets disease was selected to deep venous thrombosis of the lower limb, bipolar ulceration,
posterior uveitis, and a positive pathergy test. This is of prior myocardial infarction complicated by a ventricular fibrillation
reduced by external shock. Coronary angiography showed a threatening lesion of the anterior interventricular coronary. In the
literature, twenty cases of myocardial infarction have been reported in Behets disease. The pathophysiology, accountability
diagnostic and treatment are still difficult to explain.
Keywords: Behcet disease, myocardial infraction, coronary angiography
INTRODUCTION
Behcet disease is a disease prevalent around the Mediterranean and Japan. First case described in 1937 by
H. Behcet with a triad: oral and genital ulceration, skin
and ocular manifestations. Familial cases are rare less
than 5%, with a male predominance 7.10 for symptomatic forms, the vascular disease is found in 7-29% of
cases essentially thrombophlebitis, whereas arterial involvement is rare. Rare heart attacks are reported, myocardial infarction is a exceptional form of revelation of
the disease we present a case.
CASE REPORT
A young man of 28 years without cardiovascular risk
factor, admitted for myocardial infarction in the second day complicated by heart failure and hemodynamic instability.
Clinically on admission: TA 90/50 mmHg, heart
rate of 130 bpm, diffuse crackles in the pulmonary areas, scalable genital aphtosis.
The ECG is a QS appearance and extended anterior
ischemia (Figure 1). The immediate outcome was marked by the occurrence of ventricular fibrillation reduced by external electric shock.
Biology
Troponins to 25 times normal, Anemia: HB 7.4 g/dl,
leukocytosis at 19000 Normal kidney function, sero-
Universitary hospital of Casablanca, Morocco

2
Professor, Universitary Hospital of Casablanca, Morocco
3
Professor, Universitary Hospital of Casablanca, Morocco
Figure 1. ECG showing a myocardial infarction with ST segment elevation in

the anterior territory witn the presence of Q wave of necrosis.
logy HIV, Hepatitis B and C negative. Positive inflammation results (CRP 26 mg/l, high fibrinogen)
At the echocardiography
A very dilated left ventricle, ejection fraction at 25%
with a global hypokinesia and apical akinesia with an
adherent thrombus (Figure 2), a moderate ischemic
mitral regurgitation. The patient underwent medical
treatment with diuretics for heart failure, with a platelet antiaregant based clopidogrel and aspirin with an
Contact address:
Benhalla Hanane, Doctor
Universitary Hospital of Casablanca, Morocco
Contact phone: 00212661885875. E-mail: hanane.benhalla@yahoo.fr
Address: 23 Lotissement Lamia, Bourgogne Casablanca, Morocco.

Vol. 24, No. 4, 2014
Figure 2. Echo cardiographic Image showing a dilated left ventricle with an

adherent apical thrombus.
Benhalla Hanane et al.

Behcet disease: one of the etiologies of myocardial infarction
an uveitis was found, so the diagnosis of cardiac involvement in relation with the Behcet disease was comfirmed.
Anti phospholipid antibodies were negatives such as
the coagulation factors: protein S, protein C, ATIII.
Coronary angiography performed on the second
day of hospitalization revealed a tight stenosis of the
left anterior coronary artery with implantation of a
drug-eluting stent (Figure 3).
In collaboration with internists first bolus of Endoxan following by corticosteroid was received by the
patient, 15 days away from the acute phase of his myocardial infarction because of the risk of cardiac rupture
and possible curb after his heart failure. After the third
dose of Endoxan, the patient was slightly improved
with the medical treatment (inhibitor of angiotensin
converting enzyme-blocker-Clopidogrel-aspirin-Acenocoumarol) but with persistence of severe left ventricular dysfunction and apical thrombus.
DISCUSSION
effective anti coagulation by heparins of low molecular
weight-based enoxaparin and nitrates for the residual
angina presented by the patient. Diagnosis of Behcets
disease was suspected in cardiac involvement in a young patient in the presence of genital and oral ulceration, besides the finding of deep vein thrombosis of the
lower limb during the hospitalization: a pathergy test
came back positive, and at the ophtalmplogical control
Figure 3. Image showing a tight angiographic appearance thrombotic coronary stenosis Inter ventricular anterior.
Behcets disease is a systemic inflammatory disease

of unknown origin. It occurs mainly in young adults
with mucocutaneous, ocular, neurological and vascular
signs. The usual treatment is symptomatic, appealing to
anti-inflammatory drugs, including colchicine, immunosuppressive and / or biotherapy. It is a chronic relapsing and which it is impossible to predict the course.
As such, any physician to take care of a patient followed
for Behcets disease should be particularly vigilant in
case of unusual symptoms.
The main emergency situations to consider are:
ophthalmologic complications (at stake visual
prognosis);
vascular complications (estimated 20% mortality);
venous complications (80% of cases) or artery
(20% of cases);
neurological complications (meningoencephalitis
and cerebral venous thrombosis);
digestive perforations.
The pathogenesis of coronary artery disease in
Behets disease is explained by thrombosis coronary.
The thrombogenic risk of Behets disease is currently
known. His pathological substratum is leukocytoclastic vasculitis may cause stenosis, thrombosis or false
aneurysms1. A thrombotic coronary arteritis has been
demonstrated in some autopsy cases2,3. Orem et al.
showed that in these patients the levels of lipoprotein
Benhalla Hanane et al.

Behcet disease: one of the etiologies of myocardial infarction
Lp (a) is often high predisposing to develop thromboembolism complications4. The coagulation disorders
have been implicated with the increase of fibrinogen,
decreased fibrinolytic activity, lack of local activation
of fibrinolysis.
Spasm has been implicated especially as the coronary arteries were previously injured (leukocytoclastic
vasculitis). In the majority of cases the use of colchicine, corticosteroids and immunosuppressants was
needed for other clinical manifestations of the disease.
With a therapeutic-based calcium channel blockers to
prevent coronary spasm5.
Gullu et al.6 showed silent ischemia detected by systematic thallium scintigraphy in 25% of patients investigated with Behcets scalable. This percentage is greater
than in the control group (2.6%) so the primary prevention of complications of coronary artery disease in
Behcets still discussed.

Vol. 24, No. 4, 2014
a poor prognosis for the patient, a test of myocardial

ischemia should probably be associated with other cardiac systematic explorations.
Acknowledgments: None.
Disclosures:The authors declare that there is no conflict of interest.
References:
1.
2.
3.
4.
5.
CONCLUSION
Cardiac involvement in behcet disease remains underdiagnosed in the absence of cardiac signs and remains
6.
Huong DLT, Wechsler B, Kahn JC, Benhamou E, F Cajfinger, Godeau

P and all. Myocardial infarction in Behets disease. Arch. Evil. Heart.
1987 (11): 1663-7.
BayraktarY, Balkanci F, Kansu E, Dundar S, Uzunalimoglu B, Kayhan
B, et al. Cavernous transformation of the portal vein: a common
manifestation of Behets disease. Am J Gastroenterol.1998, 90: 14769.
Laklanpal S, Tani K, Lie JT, Katoh K, Ishigatsubo Y, Ohokubo T. and
all: Pathologic features of Behets syndrome: a review of Japanese
autopsy registry data. Hum Pathol. 1985 90: 1476-9.
Orem A, Dager O, O Memis, Bahadir S, O Ovali, Cimsit G. and all ,aLp
(a) lipoprotein levels as a predictor of risk for thrombogenic events in
patients with Behets disease. Ann Rheum Dis. 1995, 54: 726-9.
Brottier L, Barbier R, Bonnett J, Bricaud H. and all Myocardial infarction: unrecognized complication of Behcets disease. Sem Hosp Paris.
1987, 63: 2469-75.
Gullu IH, Benekli million Mudderisoglu H, Oto A, Kansu E, Kabakci
G, et al. Silent myocardial ischemia in Behet disease. J Rheumatol.
1996, 23: 323-7.
CASE PRESENTATION
Unexplained left ventricular hypertrophy, arrhythmias and

conduction disorders: take into account Anderson-Fabry Disease
(AFD). A case report of a diagnosed and under treatment AFD
in a heterozygous female, with severe left ventricular hypertrophy
and conduction disorders
Cristina Vcrescu1, Daniel Lighezan3, Monica Mangea1, Emilia Goan1, Tiberiu Ruhmann1, Drago Cozma1,2
Introduction Anderson-Fabry disease is a lysosomal disorder where alpha galactosidase deficiency causes accumulation of lipid particles in different cells, including myocardial cells, renal, endothelial cells. Cardiac and renal failure are
the main cause of death in Fabry-Anderson disease. Case report 76 y.o. female, with Anderson-Fabry disease, was diagnosed
with intermittent symptomatic second-degree atrioventricular block. Heterozygous patient with measured levels of alpha-galactosidase below normal, is following enzyme replacement therapy. The patient was previously diagnosed with renal impairment and heart disease (left bundle branch block, hypertrophic cardiomyopathy). Concentric left ventricular hypertrophy was
confirmed by the transthoracic echocardiography performed at admission (1,5 cm septum and posterior left ventricular wall
in parasternal long axis; 1,7 cm mediobasal septum in apical 4 chamber-view; severely abnormal LV mass index 219 g/m).
Unicameral pacemaker implantation was performed, with favorable evolution. Discussions It has been stated that Fabry
disease remains asymptomatic among heterozygous women; recent information shows the opposite. The patient developed
complications of the disease despite enzyme replacement therapy performed correctly since the time of diagnosis. AndersonFabry disease should be suspected in young patients with unexplained left ventricular hypertrophy, rhythm and conduction
disorders, with coexistent renal or neurological impairment.
Keywords: Fabry-Anderson Disease, unexplained left ventricular hypertrophy, arrhythmias, conduction disorders
Abstract:
Rezumat: Introducere Boala Fabry-Anderson este o maladie lizozomal n care deficitul de alfagalactozidaz determin
acumularea de particule lipidice n diverse celule din organism printre care celulele miocardice, renale, endoteliale. Afectarea
cardiac i renal reprezint principala cauz de mortalitate n boala Fabry. Prezentare de caz Pacient n vrst de 76 de ani,
cunoscut cu boala Fabry, este diagnosticat cu bloc atrioventricular gradul II Mobitz II simptomatic, intermitent. Pacienta
heterozigot, cu un nivel msurat al alfagalactozidazei plasmatice sub valoarea normal, se afl n tratament de subtituie enzimatic. Pacienta a fost diagnosticat n antecedente cu boal renal i cardiac (bloc major de ramur stng, cardiomiopatie
hipertrofic). Ecografia cardiac transtoracic efectuat la internare a confirmat hipertrofia ventricular stng concentric
(1,5 cm septul i peretele posterior n parasternal ax lung; 1,7 cm septul mediobazal n apical 4 camere; masa indexat a VS
= 219 g/m - sever anormal). S-a realizat implant de stimulator cardiac unicameral cu evoluie ulterioar favorabil. Discuii
Dei s-a considerat c boala Fabry rmne asimptomatic printre femeile heterozigote, studiile recente demonstreaz contrariul. De remarcat c pacienta a dezvoltat complicaii ale bolii n ciuda tratamentului de substituie enzimatic efectuat
corect din momentul diagnosticrii. Hipertrofia ventricular stng de cauz neexplicat asociat tulburrilor de ritm sau de
conducere, la un individ la care coexist afectare renal sau neurologic trebuie s ridice suspiciunea bolii Fabry-Anderson.
Cuvinte cheie: Boala Fabry-Andreson, hipertrofie ventricular stng de cauz neexplicat, tulburri de ritm, tulburri de
conducere
INTRODUCTION
Anderson-Fabry disease (AFD) results from hereditary
deficiency of the lysosomal enzyme -galactosidase A
(-Gal A). This disease is marked by progressive intracellular accumulation of globotriaosylceramide (Gb3)
1
Institute of Cardiovascular Diseases Timioara, Romania

2
Department of Cardiology, University of Medicine and Pharmacy Victor
Babe Timioara, Romania
3
Clinic of Cardiology, Timisoara Municipal Hospital
and digalactosylceramide, the major glycosphingolipid substrates of -galactosidase A. Many cell types
are affected, including renal epithelial cells, myocardial cells, neuronal cells, endothelial cells, pericytes, and
vascular smooth muscle cells1.
Contact address:
Vcrescu Cristina, MD, Institute of Cardiovascular Diseases,
13A, G.Adam Str., Timisoara, Romania
Tel. +40765862362
Email: vacarescucristina@yahoo.com
Cristina Vacarescu et al.

Anderson-Fabry Disease
The -galactosidase A gene is comprised of seven

exons. Molecular analyses have shown that a wide variety of molecular lesions can cause AFD; approximately 57% of disease alleles are missense mutations, 11%
nonsense mutations, 18% partial gene deletions, 6%
insertion, and 6% RNA processing defects due to aberrant splicing. Mutations are found in all seven exons.
The -galactosidase A gene defect may be associated
with no detectable enzyme activity or protein (as a result of an unstable mRNA transcript), no enzymatic
activity but detectable levels of enzyme protein (mutations that involve the catalytic site or result in improper folding of the protein), and measurable residual
-galactosidase A activity (mutations that alter protein
folding, substrate binding, or the turnover rate). The
inheritance pattern of Fabry disease is recessively Xlinked. A female carrier of the disease has a 50% chance
of transmitting the defective gene to her sons who will
develop Fabry disease. In addition, she has a 50% chance of transmitting the gene to her daughters who will be
carriers like their mother. If a male with Fabry disease
and an unaffected (non-carrier) female have children,
all of their daughters will be Fabry carriers and none of
their sons will be affected with Fabry disease2,3.
AFD is pan-ethnic, but due to its rarity, determining
an accurate disease frequency is difficult. Reported incidences, ranging from 1 in 476,000 to 1 in 117,000 in
the general population, may largely underestimate the
true prevalence. Newborn screening initiatives have
found an unexpectedly high prevalence of the disease,
as high as 1 in ~3,100 newborns in Italy and have identified a surprisingly high frequency of newborn males
with FD (approximately 1 in 1,500) in Taiwan4.
Most patients experience a long diagnostic history
before they are finally diagnosed as having Fabry disease. The deficiency of -galactosidase A is characteristic
and pathognomonic for male patients. In contrast, in
females, the situation is much more complicated due to
mainly normal or subnormal -galactosidase A activity
and a broad phenotypic spectrum, not showing a clear
genotypephenotype correlation. In males, the most
efficient and reliable method of diagnosing Fabry disease is the demonstration of deficient -galactosidase
A (-Gal A) enzyme activity in plasma, isolated leukocytes, and/or cultured cells. In females, measurement
of -Gal A enzyme activity is unreliable; although demonstration of decreased -Gal A enzyme activity is
diagnostic of the carrier state, many carrier females
have normal -Gal A enzyme activity. GLA is the only
gene in which mutations are known to cause Fabry

Vol. 24, No. 4, 2014
disease. Nearly 100% of affected males have an identifiable mutation. Molecular genetic testing is the most
reliable method of diagnosing carrier females5,6.
Clinical manifestations of Anderson-Fabry disease
include excruciating pain in the extremities (acroparesthesia), skin vessel ectasia (angiokeratoma), corneal and lenticular opacity, cardiovascular disease,
stroke and renal failure. One of the earliest and most
debilitating symptoms is the onset of acroparesthesia
in childhood. During the third and fourth decade of
life, the disease is characterized by a progressive course
and severe morbidity due to cardiac, renal and cerebrovascular involvement. One of the most severely affected organs in Fabry disease is the kidney. Renal involvement can be detected in early adulthood as mild to
heavy proteinuria and microhematuria. The majority of
patients show progressive renal failure and eventually
develop endstage renal disease. The leading cardiac
manifestation in Fabry disease is concentric left ventricular hypertrophy. Some studies report constrictive
cardiomyopathy and congestive heart failure as well as
disturbances in the conduction system with reduced
PR interval. Late cardiac manifestations are hypertrophic cardiomyopathy, myocardial ischemia, heart
failure and ventricular arrhythmias associated with
sudden cardiac death. The average age of onset for cerebrovascular symptoms in hemizygous individuals is 33
years. It includes hemiparesis, vertigo/dizziness, diplopia, dysarthria, nausea/vomiting, headache and hemiataxia. There is an elevated risk for transient ischemic
attacks, premature stroke and dementia7,8.
Enzyme replacement therapy (ERT) is available for
the treatment of Fabry disease, but it is a costly treatment. Alternative therapeutic approaches, including
small molecule chaperone therapy, are currently being
explored. ERT supplies recombinant -Gal A to cells
and reverses several of the metabolic and pathologic
abnormalities. ERT has been available for the treatment
of Fabry disease since 2001 and is administered intravenously once every two weeks. ERT has been shown to
have a positive effect on kidney and heart manifestations at an early phase of the disease, lessening pain and
improving quality of life. However, the long-term clinical benefits of ERT for Fabry patients are still unclear, especially regarding its ability to prevent premature
strokes. Therapeutic management of Fabry disease requires a multidisciplinary approach by medical specialists experienced in treating this rare condition. Such
a team approach necessitates active participation and
communication between the geneticist, nephrologist,
cardiologist, neurologist, and others9,10.

Vol. 24, No. 4, 2014

CASE REPORT
We present the case of a 76 y. o. female, who was admitted to our clinic presenting dizziness and pronounced fatigue during ordinary physical activity. The patient was diagnosed in a regional hospital with intermittent second-degree atrioventricular block with 2:1
conduction, and transferred to our clinic for pacemaker implant.
The patient was first diagnosed with AFD in 2006,
when she donated a kidney to her son. After a renal
biopsy both mother and son were diagnosed with AFD.
The son, deceased in 2010 of kidney failure, was hemizygous, and the mother is heterozygous, with a level of plasma alpha galactosidase (measured in 2006)
= 6.75 nmol/h/ml (normal values = 7-20 nmol/h/ml).
Since 2006 the patient was following enzyme replacement therapy (ERT) with Fabrazyme (agalsidase beta,
1 mg/kg body weight, once every two weeks). During
2006-2014 the patient has developed a number of complications that can be attributed to AFD. The patient
was diagnosed with chronic tubulointerstitial nephritis and stage 3 KDOQI chronic renal failure. The patient also developed hypertrophic cardiomyopathy, left
bundle branch block and first degree atrioventricular
block. The patient is also diagnosed with second degree
hypertension, type 2 diabetes balanced through diet,
dyslipidemia, cataracts on both eyes (solved by surgery).
Physical examination at admission revealed the presence of pigmented macular lesions bilaterally in the
lumbar region angiokeratoma, skin lesions typical for
AFD (Figure 1). The routine admission electrocardiography showed sinus rhythm, heart rate = 70 b/min,
first degree atrioventricular block and left bundle branch block (PR interval = 320 ms, QRS complex = 160 ms)
(Figure 2). Transthoracic echocardiography (TTE) was
performed and revealed important concentric left ventricular hypertrophy (LVH). The septum and the posterior left ventricular wall measured in parasternal long
axis were both 1,5 cm (Figure 3). In the apical 4-chamber view the mediobasal septum was 1,7 cm. The TTE
also revealed moderate left atrium (LA) dilatation: LA
surface = 20 cm2, LA volume = 72.9 ml. The patient has
a good wall motion, with a calculated ejection fraction
= 50% (telediastolic volume = 80 ml, telesistolic volume
= 40 ml), MAPSE = 1.3 cm, without significant valvular
disease. Diastolic dysfunction was confirmed by the ratio E/Em = 20 (Tissue Doppler: Em = 0.03 m/s, Pulsed
Doppler: E = 0.6 m/s, E wave fused with A wave due
to the first degree atrioventricular block). We found no
evidence of right ventricular hypertrophy.
Figure 1. Angiokeratoma - skin lesion typical for AFD.
Figure 2. The electrocardiogram performed at admission - first degree atrioventricular block, left bundle branch block.
The patient was first diagnosed with hypertension

in 2006, and since then she was under treatment with
different classes of antihypertensive drugs. During hospitalization, the patient received treatment with converting enzyme inhibitor and calcium channel blocker,
in different doses, with blood pressure values ranging
from 160 to 120 mmHg the systolic pressure and 100
70 mmHg the diastolic pressure. High blood pressure is
an important cause of left ventricular hypertrophy, but
in this case it should be noted the increased left ventri


Vol. 24, No. 4, 2014
moment the patient has a normal cholesterol level, in

the past she was diagnosed with dyslipidemia, and she
received treatment with statins. Taking in account that
the patient is also diabetic, we decided to maintain the
statin therapy (Rosuvastatin 10 mg/day).
A study published in 2009 from the Fabry Registry12
advises that all patients with Fabry disease, regardless
of age or gender, should be monitored for possible cerebrovascular complications, as stroke can occur in the
absence of other key signs of the disease. Considering
this information we decided to recommend antiplatelet
therapy (Aspirin 100 mg / day).
DISCUSSIONS
Figure 3. TTE parasternal long axis - showing concetric left ventricle hypertrophy.
IVS = interventricular septum; LVID = left ventricle internal dimension;
LVPW = left ventricle posterior wall; s systolic; d diastolic.
cular mass (367 g) and the severely abnormal LV mass

index 219 g/m2 are unusual (>122 g/m2 is severly
abnormal for a female).
The biological investigations revealed impaired renal
function, with a serum creatinine levels between 1.53
1.3 mg/dl, corresponding to stage 3 chronic renal failure. Currently the renal pathology is stationary, without
notable changes of the biological samples compared to
the last three years.
On admission, the patient presented two Holter
ECG/12 hours recordings, made in the last month,
based on which she was diagnosed with intermittent
second-degree atrioventricular block with 2:1 conduction. The AFD is mentioned in the 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization
therapy11, but in the absence of prospective trials the
guideline suggest adherence to conventional pacing indications, so the patient has a class I indication, level of
evidence C for pacemaker implant. The next day after
admission, we performed, under antibiotic protection,
single chamber pacemaker implant. We used the left
subclavian vein approach, without any intraoperatory
or postoperatory complications. The pacemaker was
programed VVI 60 beats/minute, and the patient presented intermittent pacing after implantation.
The treatment for this patient requires a multidisciplinary approach, with periodic reassessments. Regarding the cardiologic treatment we have recommended
antihypertensive therapy with converting enzyme inhibitor (Zofenoprilum 30 mg/day) and calcium channel
blocker (Lercanidipinum 10 mg/day). Although at this
Cardiac involvement is common in Fabry disease, both

in hemizygous men and heterozygous women, and it
is one of the three major causes of morbidity and mortality. Cardiac hypertrophy associated with depressed
contractility and diastolic filling impairment often
occurs. In addition, coronary insufficiency, atrioventricular conduction disturbances, arrhythmias and valvular involvement may be present. In patients with the
atypical cardiac variant, the disease manifestations
may be limited to the heart. Storage of globotriaosylceramide (Gb3) is found in various cells of the heart, including cardiomyocytes, conduction system cells, valvular fibroblasts, endothelial cells within all types of
vessels, and vascular smooth muscle cells. Gb3 storage
by itself, however, is unable to explain the observed level of cardiac hypertrophy, conduction abnormalities
and other cardiac manifestations. Autopsy of an individual with Fabry disease who had an extremely hypertrophied heart revealed a relatively limited contribution of the stored material to the enormous increase in
cardiac mass. It appears that storage induces progressive lysosomal and cellular malfunctioning that, in
turn, activates common signalling pathways leading to
hypertrophy, apoptosis, necrosis and fibrosis. A study
published in 2010 concluded that concentric LVH was
the predominant cardiac pathology seen in patients
with Fabry disease, and was prevalent in both genders
by the third decade of life. Left ventricular mass index
was inversely correlated with -Gal A activity, but was
prevalent even in younger female. A pattern of progressive involvement was also observed in the conduction
system of the heart. Early stages of the disease are associated with accelerated conduction, and late stages are
characterized by progressive bradycardia and atrioventricular conduction defects. Permanent cardiac pacing
is needed for about 10-20% of patients13-15.


Vol. 24, No. 4, 2014
Until recently, general medical textbooks have emphasized that females are largely asymptomatic. More recently published textbooks, however, reflect the changing view of the expression of Fabry disease in females.
This changing view is reflected in an on-line updated
version of Harrisons Principles of Internal Medicine,
where in May 2005 it is written that: Up to 70% of heterozygous females may exhibit clinical manifestations,
including central nervous system and cardiac disease,
but usually do not develop renal failure16.
Recent studies have shown that Fabrys disease may
be much more common among patients with left ventricular hypertrophy (LVH) than previously thought.
Up to 7% of male patients with left ventricular hypertrophy and up to 12% of female patients with unexplained LVH were found to suffer from Fabrys disease.
Thus, this disease should be considered in patients with
unexplained LVH17.
Data from 2848 patients in the Fabry Registry were
summarized to analyze the life expectancy at birth in
patients with AFD compared with the United States general population. The life expectancy of males with Fabry disease was 58.2 years, compared with 74.7 years in
the general population. The life expectancy of females
with Fabry disease was 75.4 years, compared with 80.0
years in the United States. Most (57%) patients who
died of cardiovascular disease had previously received
renal replacement therapy18.
Based upon current literature, there is evidence of
improvement with ERT in some aspects of AFD: stabilization of nephropathy with stable proteinuria and
GFR, stabilization of cardiomyopathy with stable or declining LVMI, LV wall thickness, normalization of PR
interval, reduction in neuropathic pain, improvement
or resolution of diarrhea, abdominal cramps or pain,
nausea, vomiting and heartburn associated with AFD.
The Canadian Fabry Disease Treatment Guidelines published in 2012 admits that other clinical features of Fabry disease have not been yet shown to respond to ERT:
tachy or brady arrhythmias, stroke, proteinuria, depression, hearing loss. A study published in 2013 about
the long term ERT for AFD points out that long term
ERT does not prevent disease progression, but the risk
of developing a first or second complication decreases
with increasing treatment duration. ERT in advanced
Fabry disease seems of doubtful benefit. Treatment failure also occurs frequently and seems related to age and
severe pre-treatment disease. Early diagnosis appears
to be the key to a favorable response to treatment19-21.
Take home messages: Suspected AFD when encountering young patients with a history of stroke, impaired renal function, unexplained left ventricular hyper-
trophy associated with arrhythmias or conduction disorders. Recommend plasmatic screening for AFD in
high risk patients.
Conflict of interest: none declared.
References
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Kampmann C, Baehner F, Ries M, Beck M, - Cardiac Involvement in

Anderson-Fabry Disease, JASN June1, 2002 vol. 13 no. suppl 2 S147S149
Pastores GM, Lien YHH, - Biochemical and Molecular Genetic Basis
of Fabry Disease, J Am Soc Nephrol 13:S130S133, 2002
Icahn School of Medicine at Mount Sinai, Research > Programs >
International Center for Fabry Disease > Faby Disease, http://icahn.
mssm.edu/
Germain DP, - Fabry Disease, Orphanet Journal of Rare Diseases
2010, 5:30
Havndrup O, Christiansen M, Stoevring B, i col. - Fabry disease mimicking hypertrophic cardiomyopathy: genetic screening needed for
establishing the diagnosis in women, Eur J Heart Fail (2010) 12 (6):
535-540 doi:10.1093/eurjhf/hfq073
Mehta A, Hughes DA. Fabry Disease. 2002 Aug 5, Pagon RA, Adam
MP, Ardinger HH, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from: http://
www.ncbi.nlm.nih.gov/books/NBK1292/
Whybra C, Kampmann C, Willers I, si col. - Anderson-Fabry disease:
clinical manifestations of disease in female heterozygotes. J Inherit
Metab Dis, 2001 Dec;24(7):715-24.
Breuning F, Wanner C, - Enzyme replacement therapy for Fabry disease: proving the clinical benefit, Nephrol. Dial. Transplant. (2003)
18 (1): 7-9.
Motabar O, Sidransky E, Goldin E, Zheng W, - Fabry Disease Current Treatment and New Drug Development, Curr Chem Genomics.
2010; 4: 5056.
Eng CC, Germain DP, Banikazemi M, si col. - Fabry disease: Guidelines for the evaluation and management of multi-organ system involvement, Genetics in Medicine (2006) 8, 539548;
Brignole M, Auricchio A, Baron-Esquivias G, si col, - 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy, European Heart Journal (2013) 34, 22812329,doi:10.1093/eurheartj/
eht150
Sims K, Politei J, Banikazemi M, Lee P, - Stroke in Fabry disease
frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry. Stroke
2009;40:788-794, doi: 10.1161/STROKEAHA.108.526293
Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry Disease: Perspectives from 5 Years of FOS, Oxford: Oxford PharmaGenesis; 2006.
Wu JC, Ho CY, Skali H, si col - Cardiovascular manifestations of Fabry disease: relationships between left ventricular hypertrophy, disease severity, and a -galactosidase A activity, European Heart Journal
(2010)31, 10881097
Shah J, Mehta A, Hughes D, et al. Arrhythmia in Anderson-Fabry disease. Eur Heart Journal 2004;25:539.
Deegan P, Bhner F, Barba M, Hughes DA, Beck M. - Fabry disease
in females: clinical characteristics and effects of enzyme replacement
therapy, Oxford PharmaGenesis; 2006
Linthorst GE, Vedder AC, Bouma BJ, Dekker LRC, and Hollak CEM,
- Unexplained left ventricular hypertrophy: consider a diagnosis of
Fabrys disease, Neth Heart J. Mar 2006; 14(3): 100105.
Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P. - Life expectancy
and cause of death in males and females with Fabry disease: findings
from the Fabry Registry, Genet Med. 2009 Nov;11(11):790-6.
West ML, Robin C, Clarke J, si col. Canadian Fabry Disease Treatment Guidelines 2012,
Rombach SM, Smid BE, Bouwman MG - Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and
brain. Orphanet J Rare Dis. 2013 Mar 25;8:47. doi: 10.1186/17501172-8-47.
Vedder AC, Linthorst GE, Houge G, si col. - Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose
of 0.2 mg/kg. PLoS One. 2007 Jul 11;2(7):e598.
What could hide an oncologic patient with exertional dyspnea?

Roxana Silite1, Mara Jidveian2, Raluca Ianula1, Dan Sptaru1
e present a case of a 54 years old male, referred to

our clinic for exertional dyspnea, from the Oncology Department. He was diagnosed one year before
with right upper lobe lung cancer. He underwent right upper lobectomy, lymph node dissection and right
pulmonary artery resection. The histopathologic exam
showed poorly differentiated squamous cell carcinoma
(SCC). He received four cycles of chemotherapy (Paclitaxel/CBDCA). After six month of chemotherapy, an
upper polar left renal tumor was found on abdominal
CT scan. He underwent a left nephrectomy. The histopathologic exam confirmed a SCC metastasis from the
lung cancer. He started a new chemotherapy scheme
with Docetaxel 75 mg/mp.
Six months later he was addressed to our clinic for
evaluation. He complains of progressively installed
exertional dyspnea, atypical chest pain and weight loss.
On physical examination we found normal vital signs,
no cardiomegaly, no heart murmur, no pulmonary
crackles, no edema. Laboratory tests showed mild leukocytosis, inflammatory syndrome, and high values
of NTproBNP (5300 ng/dl). CK, CKMB and troponin
were in normal range. The resting ECG revealed sinus
tachycardia and minor RBBB. The chest X-ray showed
normal cardiothoracic index, a small nodular lesion in
the right lower lobe, ascended right hemidiaphragm
and right pleural adhesion (Figure 1). The echocardio-
graphy showed normal valves, no dilation of cavities,

normal left ventricular (LV) systolic function with an
estimated EF of 60%, mild pulmonary hypertension
(sPAP= 40 mmHg) and a small pericardial effusion. In
the parasternal view we noticed in the basal segment
of the LV posterior wall a large intramyocardial mass
(2,7/4,63 m). The mass had a different echogenicity
compared to normal myocardium (Figure 2A, 2B, 2C).
Another mass, with the same echogenicity, could be
seen between left atrium (LA) and aorta (AO) (Figure
3A, B). We have also seen a small mobile mass attached to the LA roof (corresponding to above mentioned mass, as well as spontaneous contrast into the LA
(Figure 3A, B). The thoracic CT scan showed a large
intrapericardial mass (5,4/3,8 cm) with intimate contact with right pulmonary artery, aorta, left atrium,
right atrium and superior right pulmonary veins (Figure 4A). Another hypodense lesion (4,4/3,2 cm) was
seen into the myocardium of the postero-inferior LV
wall (Figure 4B). The patient received anticoagulants,
betablockers and a new chemotherapy scheme (Gemcitabine/Carboplatine). He survived only six month after
the diagnosis of intramyocardial and intrapericardial
metastasis.
Contact address:
Roxana Silite, MD
Cardiology and Internal Medicine Department, Coltea Clinical Hospital,
Bucharest; U.M.F Carol Davila
Cardiology and Internal Medicine Department, Coltea Clinical Hospital,

Bucharest; U.M.F Carol Davila
2
Oncology Department, Coltea Clinical Hospital, Bucharest
Conflict of interest: none declared.
Roxana Siliste et al.

Oncologic Patient with Dyspnea

Vol. 24, No. 4, 2014
Figure 1. Chest X ray shows a small nodular lesions in the right lower lobe (red arrow), ascended right hemidiaphragm and right pleural adhesion.
RV
LV
Ao
LA
2A
2B
2C
Figure 2. Echocardiography: parasternal long axis view (2A, 2B) and parasternal short axis view (2C) shows a large intramyocardial mass (red arrow).
(LV= left ventricle, Ao = aorta, RV = right ventricle, LA = left atrium).
3A
3B
Figure 3. Echocardiography: a left atrium optimized parasternal long axis view shows a mass between aorta (AO) and left atrium (LA) (between red arrows)
and a small mobile mass in the LA. (green arrow).
Roxana Siliste et al.

Oncologic Patient with Dyspnea
4A
Figure 4. CT scan.
4A - A pericardial mass (between red arrows), pericardial effusion (white arrow)
4B - An intramyocardical hypodense mass.

Vol. 24, No. 4, 2014
4B

Lucian Predescu1, Marin Postu1, Pavel Platon1, Mihaela Rugina1, Madalina Gavanescu1, Marian Croitoru1,
Adrian Bucsa1, Lucian Zarma1, Dan Deleanu1
We present a case of a 65 years old male patient, admitted with intermittent claudication of lower limbs at
200 meters. The cardiovascular risk factors of the patient were: stage III hypertension, dyslipidemia and smoking. The results of a clinical examination were unremarkable. A lower limbs arterial Doppler echography
was made, that showed 50-60% stenosis with calcified
plaques in both superficial femoral arteries and we proceeded to peripheral arteriography.
During the procedure, after sheath has been introduced, a local hematoma rapidly developed, which was
treated by manual compression. Terminal aorta, common and external iliac arteries, and common femoral
arteries had plaques and calcifications without significant stenosis. The angiogram showed right superficial
femoral artery blood extravasation at the level of vascular access, an abnormal image that raise the suspicion
of an extensive dissection (Figure 1), acute thrombotic

occlusion of right popliteal artery and permeable left
popliteal artery with calcified plaques (Figure 2), absent
blood flow below the right knee and normal right calf
arteries. Because the suspicion of an extensive dissection persisted, we removed the right femoral sheath and
we achieved hemostasis by manual compression. We
used a left femoral approach (5F) with cross over and
the new images invalidate the diagnosis of superficial
femoral artery dissection (Figure 3) and confirm the
acute thrombotic occlusion of right popliteal artery
(Figure 4).
Local Heart Team had to decide between: 1) thrombolysis, which is a safe and effective alternative to
surgery with a 86% success rate, but with high risk of
hemorrhagic complications1, 2) popliteal thromboaspiration, which has excellent early and mid-term results
Figure 1. Superficial femoral artery

blood extravasation at the level of
vascular access (white arrow) and an
abnormal image that raise the suspicion of an extensive dissection (black
arrow).
Figure 3. Angiogram of the right femoral artery after cross over from
the left femoral artery. There are no
signs of dissection.
Figure 2. Acute thrombotic occlusion of right popliteal artery (arrow).

Permeable left popliteal artery with
calcified athermanous plaques.
Emergency Institute for Cadiovascular Diseases Prof. Dr. C. C.

Iliescu,Bucharest, Romania
Figure 4. Acute thrombotic occlusion

of right popliteal artery with absent
blood flow below the right knee (arrow).
Contact address:
Lucian Predescu, MD
Emergency Institute for Cadiovascular Diseases Prof. Dr. C. C. Iliescu,
sos. Fundeni 258, sector 2, 022328, Bucharest, Romania.
L. Predescu et al.

Vol. 24, No. 4, 2014
Figure 5. Massive thrombus extraction after popliteal direct catheter thromboaspiration.
Figure 6. Final result - repermeabilization of right popliteal artery with minimal residual thrombus in the anterior tibial artery (arrow).
in selected cases, with short occlusions2 and 3) arterial embolectomy using Fogarty catheter. The choice
was for popliteal thromboaspiration. We used a right
common femoral artery antegrade approach, with a
7F sheath. Repetitive and progressive direct catheter
thromboaspiration using a 7F multipurpose catheter
until the level of calf arteries has been done with massive thrombus extraction (Figure 5). The final result
was good, with repermeabilization of right popliteal
artery and minimal residual thrombus in the anterior
tibial artery (Figure 6). Unfractionated heparin was
administrated for 24 hours with good clinical evolution. Thrombophilia tests were positive for a protein S
deficiency.
Although peripheral arteriography is a relatively safe
procedure (major vascular complication rate 1.9%), it
remains an invasive investigation that carries a risk of
major complications3. Its important of balancing the

risks of the procedure with the firmness of the indications and the benefits of the procedure for every patient.
Percutaneous thrombus aspiration in acute thrombotic
occlusion of the popliteal artery is an effective and safe
alternative to surgery.
Conflict of interests: none declared.

References:
1.
2.
3.
Van Damme, H., et al., Intra-arterial thrombolysis of thrombosed popliteal artery aneurysm. A series of six cases. Acta Chir Belg, 2006.
106(6): p. 679-83.
Desgranges, P., et al., Acute occlusion of popliteal and/or tibial arteries: the value of percutaneous treatment. Eur J Vasc Endovasc Surg,
2000. 20(2): p. 138-45.
Egglin, T.K., et al., Complications of peripheral arteriography: a new
system to identify patients at increased risk. J Vasc Surg, 1995. 22(6):
p. 787-94.
Ghidul european de prevenie a bolilor cardiovasculare n

practica clinic (versiunea 2012)
Al Cincilea Comitet al Societii Europene de Cardiologie i a altor Societi de
Prevenie a Bolilor Cardiovasculare n Practica Clinic (constituit din reprezentani
ai nou societi i experi invitai)
Dezvoltat cu contribuia special a Asociaiei Europene pentru Prevenie i Reabilitare
Cardiovascular (EACPR)
Autori/ Membri ai Grupului de Lucru: Joep Perk (Preedinte) (Suedia)*, Guy De Backer1 (Belgia), Helmut
Gohlke1 (Germania), Ian Graham1 (Irlanda), eljko Reiner2 (Croaia), W.M. Monique Verschuren1 (Olanda),
Christian Albus3 (Germania), Pascale Benlian1 (Frana), Gudrun Boysen4 (Danemarca), Renata Cifkova5
(Republica Ceh), Christi Deaton1 (UK), Shah Ebrahim1 (UK), Miles Fisher6 (UK), Giuseppe Germano1 (Italia),
Richard Hobbs1,7 (UK), Arno Hoes7 (Olanda), Sehnaz Karadeniz8 (Turcia), Alessandro Mezzani1 (Italia),
Eva Prescott1 (Danemarca), Lars Ryden1 (Suedia), Martin Scherer7 (Germania), Mikko Syvnne9 (Finlanda),
Wilma J.M. Scholte Op Reimer1 (Olanda), Christiaan Vrints1 (Belgia), David Wood1 (UK),
Jose Luis Zamorano1 (Spania), Faiez Zannad1 (Frana).
Ali experi care au contribuit la pri ale ghidului: Marie Therese Cooney (Irlanda).
Comitetul ESC pentru Ghiduri de Practic (CPG): Jeroen Bax (Preedinte) (Olanda), Helmut Baumgartner (Germania), Claudio Ceconi
(Italia), Veronica Dean (Frana), Christi Deaton (UK), Robert Fagard (Belgia), Christian Funck-Brentano (Frana), David Hasdai (Israel),
Arno Hoes (Olanda), Paulus Kirchhof (Germania), Juhani Knuuti (Finlanda), Philippe Kolh (Belgia), Theresa McDonagh (UK), Cyril
Moulin (Frana), Bogdan A. Popescu (Romnia), eljko Reiner (Croaia), Udo Sechtem (Germania), Per Anton Sirnes (Norvegia), Michal
Tendera (Polonia), Adam Torbicki (Polonia), Alec Vahanian (Frana), Stephan Windecker (Elveia).
Revizori ai documentului: Christian Funck-Brentano (Coordonator Revizor CPG) (Frana), Per Anton Sirnes (Coordonator Revizor
CPG) (Norvegia), Victor Aboyans (Frana), Eduardo Alegria Ezquerra (Spania), Colin Baigent (UK), Carlos Brotons (Spania), Gunilla
Burell (Suedia), Antonio Ceriello (Spania), Johan De Sutter (Belgia), Jaap Deckers (Olanda), Stefano Del Prato (Italia), Hans-Christoph
Diener (Germania), Donna Fitzsimons (UK), Zlatko Fras (Slovenia), Rainer Hambrecht (Germania), Piotr Jankowski (Polonia), Ulrich
Keil(Germania), Mike Kirby (UK), Mogens Lytken Larsen (Danemarca), Giuseppe Mancia (Italia), Athanasios J. Manolis (Grecia),
John McMurray (UK), Andrzej Pajk (Polonia), Alexander Parkhomenko (Ucraina), Loukianos Rallidis (Grecia), Fausto Rigo (Italia),
Evangelista Rocha (Portugalia), Luis Miguel Ruilope (Spania), Enno van der Velde (Olanda), Diego Vanuzzo (Italia), Margus Viigimaa
(Estonia), Massimo Volpe (Italia), Olov Wiklund (Suedia), Christian Wolpert (Germania).
Declaraiile de interese ale autorilor i revizorilor sunt disponibile pe site-ul ESC: www.escardio.org/guidelines
Societi: 1Societatea European de Cardiologie (ESC); 2Societatea European de Ateroscleroz (EAS); 3Societatea Internaional de
Medicin Comportamental (ISBM); 4Organizaia European pentru Accidentele Vaculare Cerebrale (ESO); 5Societatea European de
Hipertensiune (ESH); 6Asociaia European pentru studiul Diabetului (EASD); 7Societatea European de Medicin General/Medicin de
Familie (ESGP/ FM/WONCA); 8Federaia Internaional de Diabet - Europa (IDF-Europe); 9Reeaua European a Inimii (EHN).
Ghidurile ESC reprezint punctul de vedere al ESC i a fost conceput dup analiz atent a dovezilor disponibile la momentul elaborrii.
Medicii sunt ncurajai s-l foloseasc n momentul deciziei clinice. Ghidul nu acoper responsabilitatea individual a medicului n luarea
deciziilor adecvate, care are i responsabilitatea de a verifica regulile aplicabile substanelor medicamentoase i dispozitivelor la momentul
prescrierii lor.
* Autor corespondent: Joep Perk, School of Health and Caring Sciences, Linnaeus University, Stagneliusgatan 14, SE-391 82 Kalmar, Suedia. Tel: +46 70
3445096, Fax: +46 491 782 643, Email: joep.perk@lnu.se
Alte entiti ESC care au participat la dezvoltarea acestui document :
Asociaii: Asociaia European de Ecocardiografie (EAE), Asociaia European de Intervenii Cardiovasculare Percutane (EAPCI), Asociaia European de
Ritm cardiac (EHRA), Asociaia pentru Insuficiena Cardiac (HFA)
Grupuri de Lucru: Ingrijire Acut Cardiac, e-Cardiology, Farmacologia Cardiovascular i Terapia Medicamentoas, Hipertensiunea i Inima
Consilii: tiine Fundamentale Cardiovasculare, Practica n Cardiologie, Imagistica Cardiovascular, Ingrijirea Cardiovascular i Profesiile Afiliate, Ingrijirea Primar Cardiovascular
Ghidul european de prevenie a bolilor cardiovasculare

n practica clinic (versiunea 2012)

Vol. 24, No. 4, 2014
Coninutul acestor ghiduri ale Societii Europene de Cardiologie (ESC) a fost publicat strict n scop profesional i educaional. Utilizarea comercial nu
este autorizat. Nici o parte a Ghidului ESC nu poate fi tradus sau reprodus indiferent de forma fr permisiunea scris din partea ESC. Permisiunea
poate fi obinut prin depunerea unei solicitri scrise la Oxford University Press, editor al European Heart Journal i parte autorizat s se ocupe cu aceste
acorduri n numele ESC.
Nota. Ghidurile ESC reprezint punctul de vedere al ESC i au fost redactate dup o atent analiz a evidenelor disponibile la momentul redactrii
lor. Personalul medical este ncurajat s le foloseasc n practica lor clinic. Cu toate acestea, ghidurile nu se substituie responsabilitii individuale a
profesionitilor din domeniul sntii n luarea deciziilor potrivite n ngrijirea pacienilor. Intr, de asemenea,n responsabilitatea cadrelor medicale verificarea regulilor i reglementrilor privitoare la medicamente i dispozitive medicale, la momentul prescrierii acestora.
Declaratiile de interese ale autorilor si revizorilor sunt disponibile pe website-ul ESC www.escardio.org/guidelines
Societatea European de Cardiologie 2012. Toate drepturile rezervate. Solicitri de permisiuni se pot adresa prin email la: journals.permissions@oxfordjournals.org.
Traducere realizat de ctre membrii Grupului de lucru de Cardiologie Preventiv (n ordine alfabetic: Cornelia Clinescu (revizor), Daniel Gherasim
(revizor), Mircea Iurciuc, Florin Mitu, Dana Pop, Iulia Roca, Mihai Roca, M.I.Popescu, Adrian Tase, Mihaela Suceveanu)
Cuvinte cheie: Boli cardiovasculare Prevenie Evaluarea riscului

Managementul riscului Fumat Nutriie Activitate fizic Factori
psihosociali
CUPRINS
Abrevieri i acronime ............................................................ 302
1. Ce este prevenia bolilor cardiovasculare? ................... 303
1.1 Introducere ................................................................ 303
1.2 Dezvoltarea ghidului ................................................ 304
1.3 Metode de evaluare ................................................... 304
1.4 Combinarea metodelor de evaluare........................ 305
2. De ce este necesar prevenia bolilor cardiovasculare? .....
306
2.1 Magnitudinea problemei.......................................... 306
2.2 Prevenia bolilor cardiovasculare: o abordare pe
tot parcursul vieii ..................................................... 307
2.3 Prevenia bolilor cardiovasculare d rezultate ...... 308
2.4 Numeroase posibiliti de ameliorare .................... 309
3. Cine ar trebui s beneficieze? ........................................ 309
3.1 Strategii si estimarea riscului ................................... 309
3.1.1 Introducere ......................................................... 310
3.1.2 Strategii ............................................................... 310
3.1.3 Estimarea riscului .............................................. 311
3.2 Genetica...................................................................... 319
3.3 Vrsta i sexul ............................................................ 319
3.4 Factorii de risc psihosociali ..................................... 320
3.4.1 Factori de risc ..................................................... 321
3.4.2 Agregarea factorilor de risc psihosociali i
mecanisme bio-comportamentale................... 321
3.4.3 Evaluarea factorilor de risc psihosociali ......... 322
3.5 Ali biomarkeri pentru risc ...................................... 322
3.5.1 Factori de risc inflamatori: proteina C reactiv
nalt sensibil, fibrinogenul .............................. 323
3.5.2 Factori de risc trombotici ................................. 323
3.6 Metode imagistice n prevenia bolilor
cardiovasculare .......................................................... 323
3.6.1 Depistarea precoce prin rezonan magnetic
a bolilor cardiovasculare la pacienii
asimptomatici ..................................................... 324
3.6.2 Scorul de calciu coronarian .............................. 324
3.6.3 Ecografia carotidian ........................................ 325

3.6.4 Indicele glezn-bra ........................................... 325
3.6.5 Oftalmoscopia .................................................... 326
3.7 Alte boli cu risc crescut pentru afeciunile
cardiovasculare .......................................................... 326
3.7.1 Gripa.................................................................... 326
3.7.2 Boala renal cronic .......................................... 326
3.7.3 Sindromul de apnee n somn ........................... 327
3.7.4 Disfuncia erectil ............................................. 327
3.7.5 Bolile autoimune................................................ 327
3.7.5.1 Psoriazisul .................................................. 327
3.7.5.2 Artrita reumatoid .................................... 327
3.7.5.3 Lupusul eritematos ................................... 327
3.7.6 Parodontoza ....................................................... 328
3.7.7 Boala vascular dup radioterapie .................. 328
3.7.8 Boala vascular post transplant ....................... 328
4. Cum poate fi folosit prevenia bolilor cardiovasculare? ..
328
4.1 Principii pentru schimbarea comportamentului .. 328
4.1.1 Introducere: de ce este dificil modificarea
stilului de via? ................................................. 328
4.1.2 Comunicarea eficient i strategiile cognitivcomportamentale ca i mijloace de schimbare a
stilului de via ................................................... 328
4.1.3 Interventiile comportamentale multimodale 329
4.2 Fumatul ...................................................................... 330
4.2.1 Introducere ......................................................... 330
4.2.2 Doza i tipul ....................................................... 330
4.2.3 Fumatul pasiv ..................................................... 330
4.2.4 Mecanismul prin care fumatul crete riscul ... 330
4.2.5 Renunarea la fumat .......................................... 331
4.2.6 Intervenii farmacologice ................................. 332
4.2.7 Alte intervenii n vederea opririi fumatului.. 333
4.3 Nutriia ....................................................................... 333
4.3.1 Introducere ......................................................... 333
4.3.2 Nutrienii ............................................................ 334
4.3.3 Alimente i grupele de alimente ...................... 336
4.3.4 Alimente funcionale ........................................ 337
4.3.5 Obiceiuri alimentare ......................................... 337
4.4 Activitatea fizic ........................................................ 338

Vol. 24, No. 4, 2014
4.4.1 Introducere ......................................................... 338

4.4.2 Argumentul biologic ......................................... 338
4.4.3 Persoanele sntoase ......................................... 339
4.4.4 Pacienii cu boal cardiovascular cunoscut 340
4.5 Managementul factorilor psihosociali ................... 341
4.5.1 Introducere ......................................................... 341
4.5.2 Intervenii specifice pentru reducerea depresiei,
anxietii i strii de suferin .......................... 342
4.6 Greutatea corporal .................................................. 342
4.6.1 Introducere ......................................................... 343
4.6.2 Greutatea corporal i riscul ............................ 343
4.6.3 Care indice de obezitate este cel mai bun
predictor al riscului cardiovascular? ............... 343
4.6.4 Paradoxul obezitii n boala arterial
coronarian cunoscut...................................... 345
4.6.5 Tratament ........................................................... 345
4.7 Tensiunea arterial .................................................... 346
4.7.1 Introducere ......................................................... 346
4.7.2 Definiia i clasificarea hipertensiunii arteriale ....
346
4.7.3 Evaluarea n scop diagnostic ............................ 346
4.7.4 Msurarea tensiunii arteriale ........................... 347
4.7.5 Msurarea tensiunii arteriale la cabinet sau n
clinic .................................................................. 347
4.7.6 Monitorizarea ambulatorie i la domiciliu a
tensiunii arteriale ............................................... 347
4.7.7 Stratificarea riscului n hipertensiunea arterial ..
347
4.7.8 Pe cine tratm i cnd iniiem tratamentul
antihipertensiv ................................................... 348
4.7.9 Cum tratm ........................................................ 349
4.8 intele terapeutice la pacienii cu diabet zaharat tip 2
352
4.8.1 Introducere ......................................................... 353
4.8.2 Dovezi ale recomandrilor actuale privind
prevenirea bolilor cardiovasculare n diabet .. 353
4.8.3 Controlul glicemiei............................................ 353
4.8.4 Valorile int ale glicemiei ................................ 353
4.8.5 Meta-analize si recenzii sistematice ................ 354
4.8.6 Tensiunea arterial ............................................ 354
4.8.7 Dislipidemia ....................................................... 355
4.8.8 Terapia antitrobotic ......................................... 355
4.8.9 Microalbuminuria i interveniile
multifactoriale .................................................... 356
4.9 Lipidele ....................................................................... 356
4.9.1 Introducere ......................................................... 356
4.9.2 LDL Colesterolul................................................ 356
4.9.3 Apolipoproteina B ............................................. 357
4.9.4 Trigliceridele ...................................................... 357
4.9.5 HDL Colesterolul............................................... 357
4.9.6 Lipoproteina (a) ................................................. 357
4.9.7 Raportul apolipoprotein B/apolipoprotein A1 .
358
4.9.8 Variabilele lipoproteice calculate ..................... 358
4.9.9 Excluderea dislipidemiei secundare ................ 358

4.9.10 Cine ar trebui tratat i care sunt obiectivele? .358

4.9.11 Pacienii cu boal arterial periferic ........... 359
4.9.12 Prevenirea accidentului vascular cerebral ... 359
4.9.13 Pacienii cu boal renal ................................ 359
4.9.14 Pacienii cu transplant .................................... 359
4.9.15 Pacienii cu sindrom coronarian acut .......... 360
4.9.16 Medicamente ................................................... 360
4.9.17 Combinaii medicamentose........................... 361
4.9.18 Afereza LDL ..................................................... 361
4.10 Antitromboticele ................................................. 362
4.10.1 Terapia antiagregant plachetar la indivizii
fr boal cardiovascular manifest .............. 362
4.10.2 Terapia antiagregant plachetar la indivizii
cu boal cardiovascular sau cerebrovascular
manifest............................................................. 362
4.10.3 Tratamentul antitrombotic n fibrilaia atrial ...
363
4.10.4 Aderena ........................................................... 363
4.10.5 De ce pacienii nu ader la medicaia prescris?
363
5. Unde ar trebui s fie instituite programele de prevenie a
BCV? ................................................................................. 364
5.1 Prevenia bolilor cardiovasculare n ngrijirea
primar: rolul asistentei medicale ........................... 365
5.1.1 Programe de prevenie coordonate de asisteni
medicali eficiente n diferite sisteme de sntate..
365
5.1.2 Legtura continu este necesar pentru
modificarea stilului de via ............................. 366
5.2 Prevenia bolilor cardiovasculare n practica
general ...................................................................... 367
5.2.1 Identificarea persoanelor la risc....................... 367
5.2.2 Utilizarea scorurilor de risc n practica clinic.....
367
5.2.3 Obstacole n implementarea evalurii de rutin
a riscului cardiovascular ................................... 367
5.2.4 Metode pentru mbuntirea gradului de
contientizare i de implementare a calculrii
scorului de risc ................................................... 368
5.2.5 mbuntirea managementului factorilor de risc
368
5.3 Prevenia bolii cardiovasculare n ngrijirea primar:
rolul cardiologului .................................................... 369
5.3.1 Cardiologul n practica general: rol de
consultant ........................................................... 369
5.3.2 Implementarea medicinei bazate pe dovezi ... 369
5.3.3 mbuntirea serviciilor medicale prin folosirea
unei baze de date electronice ........................... 369
5.4 Programe de autongrijire ........................................ 370
5.5 Programe care se bazeaz pe serviciile oferite n
spitale .......................................................................... 371
5.5.1 Necesitatea recomandrilor bazate pe dovezi la
externare pentru un tratament optim ............. 371
5.5.2 Programele de mbuntire sistematic a
calitii serviciilor medicale sunt eseniale..... 371

5.6 Programe n spital: centre de prevenie specializate ....

372
5.6.1 Centrele de recuperare cardiac ajut la
mbuntirea stilului de via ......................... 372
5.6.2 Recuperarea cardiac este cost-eficient ........ 372
5.6.3 Provocri pentru recuperarea cardiac: sexul
feminin i comorbiditile ................................ 372
5.6.4 Sesiunile repetate mbuntesc compliana .. 373
5.7 Programele organizaiilor non-guvernamentale... 373
5.8 Aciunea de la nivel politic european ..................... 373
Bibliografie ............................................................................ 374
ABREVIERI I ACRONIME
ACCORD
Action to Control Cardiovascular Risk

in Diabetes
ADVANCE
Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
AGREE
Appraisal of Guidelines Research and
Evaluation
AHA
American Heart Association
apoA1
apolipoproteina A1
apo B
apolipoproteina B
BPAC
by-pass aorto-coronarian
CARDS
Collaborative AtoRvastatin Diabetes
Study
CCNAP
Council on Cardiovascular Nursing
and Allied Professions
CHARISMA Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation,
Management, and Avoidance
BCI
boal coronarian ischemic
BRC
boal renal cronic
COMMIT
Clopidogrel and Metoprolol in Myocardial Infarction Trial
CURE
Clopidogrel in Unstable Angina to
Prevent Recurrent Events
BCV
boal cardiovascular
DALYs
ani de via pierdui prin disabilitate
DCCT
Diabetes Control and Complications
Trial
DE
disfuncie erectil
eGFR
rata de filtrare glomerulara estimat
EHN
European Heart Network
EPIC
European Prospective Investigation
into Cancer and Nutrition
EUROASPIRE European Action on Secondary and
Primary Prevention through Intervention to Reduce Events
GFR
rata de filtrare glomerular
GOSPEL
Global Secondary Prevention Strate

Vol. 24, No. 4, 2014
GRADE
HbA1c
HDL
HF-ACTION
HOT
HPS
HR
hsCRP
HVS
HYVET
ICD
IGB
IMT
INVEST
JTF
LDL
Lp(a)
LpPLA2
MATCH
MDRD
MET
MONICA
NICE
NRT
NSTEMI
ONTARGET
OSA
OMS
PAD
PCI
PCR
PROactive
gies to Limit Event Recurrence After

MI
Grading of Recommendations Assessment, Development and Evaluation
Hemoglobina glicozilat
high-density lipoprotein
Heart Failure and A Controlled Trial
Investigating Outcomes of Exercise
TraiNing
Hypertension Optimal Treatment
Study
Heart Protection Study
hazard ratio
proteina C reactiv cu nalt sensibilitate
hipertrofie ventricular stng
Hypertension in the Very Elderly Trial
Clasificarea Internationala a Bolilor
indice glezn-bra
indicele intim-medie
International Verapamil SR/Trandolapril
Joint Task Force
low-density lipoprotein
lipoproteina (a)
fosfolipaza 2 asociata lipoproteinei
Management of Atherothrombosis
with Clopidogrel in High-risk Patients
with Recent Transient Ischaemic Attack or Ischaemic Stroke
Modification of Diet in Renal Disease
echivalent metabolic
Multinational MONItoring of trends
and determinants in Cardiovascular
disease
National Institute of Health and Clinical Excellence
terapie de substituie nicotinic
infarct miocardic fr supradenivelare
de segment ST
Ongoing Telmisartan Alone and in
combination with Ramipril Global
Endpoint Trial
sindrom de apnee n somn
Organizaia Mondial a Sntii
boal arterial periferic
intervenie coronarian percutan
proteina C reactiv
Prospective Pioglitazone Clinical Trial
in Macrovascular Events

Vol. 24, No. 4, 2014
PWV
QOF
RCT
RR
SCORE
SEARCH
SHEP
STEMI
SU.FOLOM3
TNT
TAS
TAD
UKPDS
VADT
VALUE
VITATOPS
VLDL
velocitatea undei de puls

Quality and Outcomes Framework
trial clinic randomizat
risc relativ
Systematic Coronary Risk Evaluation
Project
Study of the Effectiveness of Additional Reductions in Cholesterol
Systolic Hypertension in the Elderly
Program
infarct miocardic cu supradenivelare
de segment ST
SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty
acids Syst-Eur Systolic Hypertension
in Europe
Treating to New Targets
tensiunea arterial sistolic
tensiunea arterial diastolic
United Kingdom Prospective Diabetes
Study
Veterans Affairs Diabetes Trial
Valsartan Antihypertensive Longterm Use
VITAmins TO Prevent Stroke
very low-density lipoprotein
I. CE ESTE PREVENIA BOLILOR CARDIOVASCULARE?

1.1 Introducere
Boala cardiovascular aterosclerotic (BCV) este o
boal cronic ce se dezvolt insidios pe parcursul vieii
i de obicei progreseaz pn la un stadiu avansat nainte de apariia simptomelor. Rmne cauza major de
deces prematur n Europa, chiar dac mortalitatea prin
BCV a sczut considerabil n ultimele decenii n multe ri europene. Se estimeaz c n momentul de fa
peste 80% din decesele prin BCV apar n rile n curs
de dezvoltare.
BCV determin dizabiliti majore: n urmtoarele
decenii, anii de via pierdui prin dizabilitate (DALYs)
sunt estimai s creasc de la o pierdere de aproximativ 85 de milioane DALYs in 1990 la o pierdere de
aproximativ 150 milioane DALYs global n 2020, rmnnd astfel cauza somatic principal de pierdere a
productivitii1.
BCV este strns corelat cu stilul de via, mai ales
cu utilizarea tutunului, obiceiurile alimentare nesntoase, inactivitatea fizic i stressul psihosocial2. Organizaia Mondial a Sntii (OMS) a declarat c peste

trei sferturi din toate decesele cauzate de BCV ar putea fi prevenite prin schimbri adecvate ale stilului de
via. Prevenia BCV, rmnnd o provocare major n
egal msur pentru populaia general, politicieni i
cei care lucreaz n sistemul de sntate, este definit
ca fiind un set de aciuni coordonate, la nivel public i
individual, cu scopul de a eradica, elimina sau minimiza impactul bolilor cardiovasculare i a disabilitilor
care le nsoesc. Bazele preveniei sunt nrdcinate n
epidemiologie i n medicina bazat pe dovezi3.
Scopul ghidului din 2012 de la a 5-a reuniune a grupului de lucru (JTF) a Societilor Europene pentru
Prevenia Bolilor Cardiovasculare n Practica Clinic
este de a actualiza cunotinele actuale n cardiologia
preventiv, ale medicilor i ale altor categorii profesionale din domeniul sntii. Documentul difer de
ghidul din 2007 prin mai multe aspecte: se pune un
accent mai mare asupra unor noi cunotine stiinifice.
Utilizarea sistemelor de clasificare [European Society
of Cardiology (ESC) and Grading of Recommendations
Assessment, Development, and Evaluation (GRADE)]
permite ca mai multe recomandri bazate pe dovezi s
fie adaptate necesitilor din practica clinic.
Cititorul va gasi rspunsuri la ntrebari cheie n ceea
ce privete prevenia BCV, n cinci seciuni: ce este prevenia BCV, de ce este necesar, cine ar trebui s beneficieze de ea, cum poate fi aplicat prevenia BCV i cnd
este momentul oportun pentru a interveni i n fine,
unde ar trebui recomandate programele de prevenie.
O documentare din literatur asupra ghidurilor clinice avnd ca scop evaluarea riscului cardiovascular
n practica clinic a identificat peste 1900 publicaii4.
Cnd acestea au fost evaluate utiliznd instrumentul de
evaluare Appraisal of Guidelines Re-search and Evaluation (AGREE), doar apte au ndeplinit nivelul de rigoare de considerat. Prea multe ghiduri i prea puin
impact? Distana dintre cunostinele de ultim or i
implementarea lor n practica clinic rmne mare,
dup cum au artat ultimele studii precum EUROASPIRE III5. Medicii de familie ar putea fi copleii de numeroasele recomandri din domeniul larg al medicinii
de familie. A gsi timp pentru a citi i a implementa
multiplele ghiduri poate fi o sarcin suprasolicitant
ntr-un centru aglomerat de ngrijiri primare sau ntrun spital regional.
Grupul de lucru care a elaborat recomandrile din
2012 a ales s limiteze dimensiunea la nivelul unui rezumat al publicaiilor JTF anterioare. Toate materialele
de referin relevante sunt disponibile pe pagina dedicat pentru Ghidul de prevenie a BCV a website-ului

ESC (www.escardio.org/guidelines). Va exista un rezumat de o pagin a tuturor recomandrilor importante

conform sistemului GRADE, care ar putea stimula implementarea; va fi disponibil i o versiune de buzunar
pentru utilizarea clinic zilnic.
1.2 Dezvoltarea ghidurilor
Primele recomandri (1994) reflectau nevoia unui
consens din partea ESC, Societii Europene de Ateroscleroz i a Societii Europene pentru Hipertensiune
i pledau pentru evaluarea riscului total n prevenia
primar. O revizuire a fost publicat n 1998 de al doilea JTF care a inclus cele trei societi menionate la
care s-au adugat Societatea European pentru Medicin General/Medicin de Familie, Reeaua European
a Inimii (EHN) i Societatea Internaional de Medicin Comportamental.
Apreciind c era necesar un nivel i mai larg de expertiz, al treilea JTF a fost extins pentru a include opt
societi: s-au alturat Asociaia European pentru Studiul Diabetului i Federaia Internaional pentru Diabet-Europa. Al treilea JTF a lrgit recomandrile de la
cele pentru boala coronarian ischemic (BCI), la cele
pentru BCV i a introdus conceptul de evaluare a riscului total pentru BCV utiliznd baza de date SCORE
(Systematic Coronary Risk Evaluation Project).
Tabele de risc speciale bazate pe SCORE au fost produse att pentru rile cu risc mic ct i pentru cele cu
risc nalt i au fost larg acceptate n toat Europa. Conceptul de prevenie primar i secundar a fost nlocuit
cu recunoaterea faptului c ateroscleroza este un proces continuu. Au fost propuse prioriti pe patru niveluri: pacieni cu boal diagnosticat, indivizi asimptomatici cu risc nalt de mortalitate prin BCV, rudele de
gradul nti ale pacienilor cu BCV prematur i ali
indivizi ntlnii n practica clinic de rutin.
n actualizarea din 2007, al patrulea JTF reflect
consensul a nou societi tiinifice, adugndu-se
grupului i Iniiativa European pentru Accidentul
Vascular Cerebral. Din partea ESC, Asociaia European Pentru Prevenie i Reabilitare Cardiovascular a
contribuit cu specialiti din domeniile: epidemiologie,
prevenie i reabilitare. Noutile au fost legate de o
contribuie crescut din partea medicilor de familie si a
asistentelor din domeniul cardiovascular, fiind elemente cheie n implementarea preveniei. I s-a acordat
o mai mare importan consilierii n ceea ce privete
stilul de via, i a fost revizuit abordarea riscului de
BCV la tineri, utiliznd tabelele de risc relativ SCORE.
Actualizarea actual din partea celui de-al cincilea
JTF reflect consensul asupra aspectelor mai largi ale

Vol. 24, No. 4, 2014
preveniei BCV din partea a nou organizaii participante. Pentru recomandri mai detaliate, sunt fcute
referine la ghidurile specifice din partea societilor
participante, care sunt n deplin acord cu aceast publicaie.
Societile partenere coopereaz prin Comitetul Societilor de Implementare, care are ca scop stimularea
rspndirii ghidurilor, acceptarea lor la nivel naional i
formarea de aliane naionale pentru a transpune recomandrile n practica clinic. Programul Call for Action a fost unul din eforturile acestui comitet6.
Implementarea a fost bine primit la nivel politic la
nivelul Uniunii Europene (EU) dup lansarea European
Heart Health Charter n Parlamentul European n iunie 20076. Aceast declaraie de sntate public a fost
susinut de majoritatea statelor membre EU, definind
profilul unui individ pentru meninerea strii de sntate:
Nefumtor
Activitate fizic adecvat: cel puin 30 minute, de
cinci ori pe sptmn
Obiceiuri alimentare sntoase
Fr exces ponderal
Tensiunea arterial sub 140/90 mmHg
Colesterolul seric sub 5 mml/l (190 mg/dl)
Metabolism normal al glucozei
Evitarea stresului excesiv
1.3 Metode de evaluare
Un ghid bun reprezint un mecanism important
pentru mbuntirea serviciilor de sntate i pentru
ameliorarea prognosticului pacienilor7. Ghidurile bazate pe dovezi credibile au o probabilitate mai mare de
a fi implementate n practica clinic8. Ghidul actual urmeaz criteriile de calitate pentru dezvoltarea ghidurilor, care pot fi gsite pe www.escardio.org/ knowledge/
guidelines/rules.
Pe scurt, experii a nou organizaii au efectuat o
recenzie extensiv i o evaluare critic a procedurilor
diagnostice i terapeutice, inclusiv evaluarea raportului
risc/beneficiu. Nivelul de eviden i clasa de recomandare au fost gradate conform recomandrilor ESC (Tabelele 1 i 2).
Declaraiile pentru conflictele de interese ale grupului de lucru sunt disponibile pe website-ul ESC. Modificri n conflictele de interese care au aprut n timpul
perioadei de scriere au fost notificate.
Pregtirea i publicarea raportului celui de-al cincilea JTF a fost suportat financiar de ctre ESC fr implicarea vreunei firme farmaceutice. Odat ce documentul
a fost finalizat de catre experii celui de-al cincilea JTF,


Vol. 24, No. 4, 2014
a fost prezentat pentru o revizuire extern extensiv independent. Dup aceast revizuire i dup acceptarea
de ctre Comitetului ESC pentru Ghidurile de Practic
Clinic i organizaiile care au cooperat cu al cincilea
JTF, documentul a fost publicat.
1.4 Combinarea metodelor de evaluare
O noutate important n evaluarea calitii dovezilor
i stabilirea recomandrilor o reprezint folosirea att a
metodei de evaluare recomandat de ESC, ct i a sistemului de rating GRADE9. Spre deosebire de ghidurile
din 2007, comitetul JTF a ales s ofere recomandri folosind ambele sisteme, astfel nct cititorii familiarizai
cu vechea metod i cei care prefer GRADE s gseasc recomandrile adaptate cerinelor lor, dar congruente, n tabelele de recomandri combinate.
JTF a introdus sistemul GRADE deoarece acesta folosete un proces transparent i riguros pentru evaluarea calitii dovezilor, lund n cosiderare dac cercetri ulterioare ar schimba sau nu gradul de ncredere
n efectele interveniei sau acurateea diagnosticului10.
Indicatori de calitate specifici sunt: limitrile studiului;
inconsistena rezultatelor; caracterul indirect al dovezilor; imprecizia; i eroarea (bias) legat de publicare (Tabelul 3). Acestea sunt aplicate fiecrui rezultat de importan critic pentru procesul decizional, n aprecierea grupului de redactori ai ghidului (de ex. reducerea
evenimentelor clinice este de obicei critic; modificarea
variabilelor biochimice nu este de regul critic). Ulterior, n funcie de aceti indicatori, se apreciaz ca-
litatea dovezilor ca fiind nalt (este puin probabil ca

cercetri ulterioare s schimbe ncrederea n estimarea
efectului), moderat, sczut, sau foarte sczut. Aceast apreciere se realizeaz n funcie de calitatea dovezilor pentru rezultatele critice, i nu pentru cele care nu
sunt critice pentru procesul decizional.
Valoarea acestei noi abordri const n faptul c dovezile din articolele de bilan (review-uri) sau din trialuri clinice randomizate (RCT) care sunt inconsistente,
imprecise, sau cu diverse surse de eroare pot fi retrogradate din categoria dovezilor de calitate nalt n cele
cu calitate moderat sau joas. n mod similar, date observaionale din studii de cohort sau caz-control pot
fi trecute din categoria moderat sau joas (ca n cazul
vechii abordri pe nivele-de-eviden) la calitate nalt
dac erorile sunt puin probabile, i rezultatele sunt coerente i exacte. Acest fapt este foarte util n evaluarea
dovezilor n domeniul preveniei cardiovasculare, unde
studiile clinice randomizate asupra stilului de via sntos sunt dificil de efectuat i pot fi neltoare.
Metoda GRADE face de asemenea diferena ntre
calitatea dovezilor i gradul de recomandare9. Dovezi
puternice nu duc neaprat la recomandri ferme. Recomandrile se bazeaz pe calitatea dovezilor, gradul
de incertitudine asupra raportului risc-beneficii al interveniei, incertitudinea asupra valorilor i preferinelor pacientului, i incertitudinea dac intervenia reprezint o utilizare justificat a resurselor. n locul mai
multor clase de recomandri (de ex. Clas I-Clas III),
sistemul GRADE folosete doar dou categorii reco-
Tabelul 1. Clase de recomandri

Clasa de recomandare
Definiie
Clasa I
Dovezi sau/i acord general cu privire la faptul c un anumit tratament sau procedur sunt benefice, utile, eficiente.
Clasa II
Dovezi contradictorii sau/i divergen de opinii asupra utilitii/eficacitii unui anume tratament sau proceduri
Clasa II a
Dovada/opinia este mai degrab n favoarea utilitii/eficienei
Clasa II b
Utilitatea/eficiena este mai puin susinut de dovezi/opinii
Dovezi sau acord general c un anume tratament sau procedur nu este util/eficace i n anumite cazuri poate fi chiar
Clasa III
duntoare
Tabelul 2. Nivel de eviden

Nivel de eviden A
Nivel de evident B
Nivel de eviden C
Sugestii pentru utilizare

Este recomandat/este indicat
Ar trebui luat n considerare
Poate fi luat n considerare
Nu este recomandat
Date derivate din multiple trialuri clinice randomizate sau meta-analize

Date derivate dintr-un singur trial clinic randomizat
sau din studii largi non-randomizate
Consens de opinii ale experilor sau/i studii mici, studii retrospective, registre
Tabelul 3. Categoriile folosite n GRADE pentru calitatea dovezilor9

Limitrile studiului
Alocarea pe grupuri nu este inut secret; evaluarea rezultatului nu se face n orb; pierderea unui numar mare de pacieni la urmrire;fr analiz intenie
de a trata (intention-to-treat)
Rezultate inconsistente
Variabilitate datorat diferenelor ntre pacienii studiai, intervenii, rezultate evaluate.
Caracterul indirect al dovezilor
Comparaia cap la cap (head-to-head) este direct; intervenia A vs control i B vs control este indirect n evaluarea A vs B
Imprecizia
Numr mic de pacieni, ceea ce duce la intervale de ncredere mari
Eroarea de publicare (publication bias)
De regul studiile clinice care arat c intervenia nu a avut nici un efect nu sunt publicate, sau sunt publicate n jurnale locale neindexate.

mandri puternice sau slabe (care sunt facultative sau

condiionale). Implicaiile unei recomandri puternice:
majoritatea pacienilor informai ar alege intervenia
recomandat (i ar solicita discuia despre aceasta dac
nu li s-ar oferi opiunea); clinicienii ar trebui s se asigure c majoritatea pacienilor au parte de intervenie;
i recomandarea ar fi adoptat ca politic de sistemele
de sntate. n schimb, n cazul recomandrilor slabe,
unii pacieni ar dori intervenia, dar majoritatea nu; clinicienii ar alege pacienii s aleag n funcie de valorile
i preferinele individuale; responsabilii de politicile de
sntate ar cere dezbateri ntre diferiii factori implicai, nainte de a decide asupra rolului interveniei.
Metoda GRADE poate fi aplicat strategiilor diagnostice n acelai mod, cu cteva modificri minore
ale criteriilor de calitate folosite9, i poate fi folosit i
alturi de evaluarea utilizrii resurselor i a eficienei
n privina costurilor10. Totui, cum resursele sunt evaluate diferit n diverse pri ale Europei, nu este fezabil
ca n acest ghid s se formuleze judeci asupra folosirii
adecvate a resurselor pentru interveniile i strategiile
de diagnostic luate n considerare aici.
2. DE CE ESTE NEVOIE DE PREVENIA BOLILOR

CARDIOVASCULARE?
Mesaje eseniale
BCV aterosclerotic, n special BC, rmne principala cauz de decese premature la nivel mondial.
BCV afecteaz i brbaii i femeile; dintre toate
decesele sub vrsta de 75 ani, din Europa, 42% se
datoreaz BC la femei i 38% la brbai.
Mortalitatea prin BCV este n curs de schimbare,
cu scderea ratelor mortalitii standardizate n
funcie de vrst n majoritatea rilor europene,
rmnnd ridicate n Europa de Est.
Prevenia este eficient: >50% din scderea mortalitii prin BCI se datoreaz interveniei asupra
factorilor de risc, i 40% mbuntirii tratamentelor.
Eforturile de prevenie ar trebui s dureze toat
viaa, de la natere (dac nu chiar mai devreme)
pn la vrstele naintate.
Strategiile de prevenie la nivel populaional i
cele pentru categoria de risc nalt trebuie s fie
complementare; eficiena este mai sczut dac
se au n vedere doar persoanele cu risc crescut;
este nc nevoie de programe de educare a populaiei.
Dei unele chestiuni rmn incomplet nelese,
exist numeroase dovezi care s justifice efortu

Vol. 24, No. 4, 2014
rile intense de prevenie la nivelul sntii publice i la nivel individual.

nc mai pot fi aduse ameliorri semnificative n
controlul factorilor de risc, chiar i la persoanele
cu risc crescut.
2.1 Magnitudinea problemei

Boala coronarian (BC) reprezint astzi principala cauz de mortalitate la nivel mondial; este n cretere
i a atins proporiile unei pandemii care nu cunoate
granie. Aceast afirmaie de pe site-ul OMS11, din
2009, nu difer mult de avertizrile emise n 1969 de
Comitetul Executiv al OMS: Cea mai important epidemie pe care a cunoscut-o umanitatea: BC este de proporii enorme, afectnd tot mai din ce n ce mai mult
subiecii tineri. Va duce n anii care urmeaz la cea mai
mare epidemie cu care s-a confruntat umanitatea, dac
nu vom reui s inversm aceast tendin prin cercetri intense asupra cauzei i preveniei BCI12. Cea de-a
doua BCV accidentul vascular cerebral reprezint
o alt important cauz de mortalitate i morbiditate.
Din acest motiv, al cincilea ghid emis de JTF se refer la
toate manifestrile BCV aterosclerotice.
Decizia de a evalua BCV aterosclerotic n totalitatea manifestrilor ei ar putea da impresia c nimic nu
s-a schimbat n ultimii 40 ani, ceea ce nu este adevrat.
Dimpotriv, epidemia a fost i este nc extrem de dinamic i este influenat att de modificrile factorilor
de risc cardiovascular, ct i de creterea oportunitii
interveniilor intite n domeniul preveniei i al tratamentului BCV. Aceasta duce la fluctuaii n ambele sensuri ale morbiditii i mortalitii cardiovasculare pe
perioade scurte de timp, cu o mare variabilitate la nivel
global, incluznd i rile n curs de dezvoltare, unde e
cea mai mare proporie de evenimente cardiovasculare.
n diverse pri ale globului, dinamica epidemiei variaz mult ca evoluie specific, magnitudine, i distribuie n timp13. n Europa, ponderea BCV rmne nsemnat: acestea rmn o cauz important de decese
premature i pierderi de DALY (disease adjusted life
years) un indicator compus care nsumeaz decesele
premature i perioada de via afectat de boal. Nu se
acord destul importan faptului c BCV reprezint
principala cauz de deces prematur la femei: BVC a fost
responsabil de 42% din totalul deceselor sub 75 ani la
femeile din Europa i de 38% din totalul deceselor sub
75 ani la brbai14. Totui, n numeroase ri europene
s-a observat o scdere a mortalitii standardizate n
funcie de vrst, datorate BC i BCV, ntre anii 1970
i anii 1990, cu scderea cea mai timpurie i cea mai
important n rile mai bogate, ceea ce ilustreaz posi-

Vol. 24, No. 4, 2014
bilitatea prevenirii deceselor premature i a prelungirii

speranei de via n condiii de sntate. n mai multe
ri est-europene, totui, mortalitatea prin BCV i BC
rmne ridicat15.
Responsabilii de politicile de sntate public trebuie s tie dac principalii factori care contribuie la
morbiditate i mortalitate precum BCV sunt n cretere
sau n scdere. Este nevoie n permanen de o descriere corect i actualizat a epidemiei, tinnd cont de
loc, timp, i caracteristici personale, pentru ghidarea i
susinerea politicilor de sntate public.
n prezent nu exist nici o surs standardizat la nivelul ntregii Europe care s furnizeze date de morbiditate a BCV. Rezultatele proiectului MONICA (MONitoring of trends and determinants in CArdiovascular
disease) au indicat o tendin heterogen a incidenei
BCV n Europa n anii 1980 i 199016. Se poate ca acest
tablou s se fi schimbat, i rezultatele rapoartelor recente sugereaz ntr-adevr c mortalitatea i morbiditatea
prin BCV sunt staionare, mai ales n rndurile adulilor tineri17, 18. Ar trebui s nelegem, de asemenea, c
datorit mbtrnirii populaiei i a creterii ratei de supravieuire n sindroamele coronariene acute, numrul
total al persoanelor care triesc cu BCV crete. Majoritatea acestor pacieni dezvolt boala la o vrst naintat, ducnd la fenomenul de compresie a morbiditii
n grupul persoanelor foarte vrstnice i la creterea
speranei de via ntr-o stare de sntate bun. Baza
de date Global Health Observatory a OMS (http://apps.
who.int/ghodata/?vid=2510) furnizeaz date privind
ratele mortalitii prin BCV n prezent, la nivel global.
2.2 Prevenia bolilor cardiovasculare:
o abordare pe tot parcursul vieii
Prevenia BCV ncepe n mod ideal n cursul sarcinii
i dureaz pn la sfritul vieii. n practica curent,
eforturile de prevenie se adreseaz de regul brbailor
i femeilor de vrst mijlocie sau mai mare, care prezint deja BCV (prevenie secundar) i persoanelor la
risc nalt de a dezvolta un prim eveniment cardiovascular [de ex. persoanelor care prezint combinaia fumat,
tensiune arterial (TA) crescut, diabet sau dislipidemie (prevenie primar)]; prevenia BCV la tineri, la
cei foarte vrstnici sau la persoanele cu un risc mic sau
moderat este nc limitat, dar poate aduce beneficii
semnificative. Prevenia este mprit tipic n prevenie primar sau secundar, dei n BCV distincia ntre
cele dou este arbitrar, avnd n vedere evoluia continu a procesului aterosclerotic care st la baza acestor afeciuni. De la recomandrile lui Geoffrey Rose
din urm cu cteva decenii, se iau n considerare dou

abordri ale preveniei BCV: strategia populaional i

strategia riscului nalt19.
Strategia populaional i propune s reduc incidena BCV n populaie prin modificri ale stilului de
via i ale mediului, adresndu-se ntregii populaii.
Aceast strategie este realizat n principal prin aplicarea unor politici ad-hoc i a unor intervenii comunitare. Ca exemplu se pot da msurile de interzicere a fumatului i reducerea coninutului de sare din alimente.
Avantajul este c se pot aduce mari beneficii populaiei,
dei ofer prea puin individului. Impactul unor asemenea abordri asupra numrului total de evenimente
cardiovasculare n populaie poate fi semnificativ, deoarece se adreseaz tuturor persoanelor, iar majoritatea
evenimentelor au loc n grupul numeros al persoanelor
care au doar un risc modest.
n strategia riscului nalt, msurile preventive i
propun s reduc nivelul factorilor de risc la persoanele cu risc crescut, fie indivizi fr BCV dar n partea
de sus a distribuiei riscului cardiovascular, fie indivizi
cu BCV manifest. Dei persoanele crora li se adreseaz aceast strategie au anse mai mari s beneficieze
de interveniile preventive, impactul la nivel populaional este mic, deoarece sunt puine astfel de persoane cu
risc crescut. Timp ndelungat, strategia populaional a
fost considerat mai eficient la nivelul costurilor dect
strategia riscului nalt, dar odat cu apariia unor medicamente hipolipemiante foarte eficiente, mbuntirea
programelor de renunare la fumat i scderea costului
medicamentelor antihipertensive, eficiena strategiei
riscului nalt a crescut20. Exist un consens c efectul
preventiv cel mai mare se obine prin combinarea acestor dou abordri.
Este important de semnalat acumularea n ultimele decenii a dovezilor c riscul cardiovascular crescut
apare la vrste (foarte) tinere. Chiar i expunerea nainte de natere la factorii de risc poate influena riscul
cardiovascular pe parcursul ntregii viei21, dup cum
arat studiile pe copiii femeilor care erau nsrcinate n
timpul foametei din al doilea rzboi mondial n Olanda22. Dei copiii au un risc absolut foarte mic pentru
BCV, cei care au un risc relativ crescut comparativ cu
persoane de aceeai vrst, rmn cu un risc crescut de
apariie a unor evenimente cardiovasculare mai trziu
n via, datorit trenrii factorilor de risc (indivizii
aflai spre limita superioar a distribuiei unui factor de
risc la vrste tinere au tendina de a rmne n partea
superioar a distribuiei)23. Prin urmare, un stil de via
sntos la tineri este esenial, dei diverse motive, printre care cele etice, mpiedic acumularea unor nivele
puternice de eviden bazate pe studii clinice randomi

zate privind beneficiile, n termeni de reducerea a incidenei BCV, de exemplu programele colare de educaie
pentru sntate sau aciuni avnd drept scop renunarea la fumat. De asemenea, atenia sczut acordat
preveniei BCV la vrstnici s-a dovedit nejustificat.
Studiile au artat c msurile preventive (cum ar fi scderea TA sau ncetarea fumatului) sunt benefice pn la
vrste avansate24,25. Aceste fapte dovedesc c eforturile
preveniei cardiovasculare ar trebui s se ntind de-a
lungul ntregii viei, dei efectele benefice n termeni
de, spre exemplu, scderea incidenei evenimentelor
cardiovasculare fatale i non-fatale sau ameliorarea calitii vieii, ar trebui ntotdeauna comparate cu potenialele efecte nocive pe care le pot avea msurile specifice (cum ar fi efectele secundare ale medicamentelor sau
efectele psihologice ale etichetrii unor indivizi sntoi drept pacieni) i cu costurile implicate.
2.3 Prevenia bolilor cardiovasculare d rezultate
Pentru a putea interpreta dinamica epidemiei BCV,
este important s difereniem efectul reducerii ratei de
mortalitate a unui eveniment acut de schimbrile datorate prevenirii apariiei evenimentelor clinice. Unii
autori atribuie meritul folosirii pe scar tot mai larg
a tratamentelor bazate pe dovezi cum ar fi tromboliza,
aspirina, inhibitorii enzimei de conversie a angiotensinei (IEC), interveniilor coronariene percutane (PCI),
i chirurgia de by-pass aorto-coronarian (BPAC)26,27, n
timp ce alii atribuie meritul ameliorrii managementului factorilor majori de risc cum ar fi fumatul, hipertensiunea, i dislipidemia28.
Proiectul MONICA, derulat n anii 1980 i 1990, a
artat c doar o parte din variaia n timp a tendinelor ratelor evenimentelor coronariene pot fi prezise n
funcie de variaia factorilor de risc16. A existat o relaie
important ntre modificrile scorurilor factorilor de
risc i modificrile ratelor evenimentelor; variaia factorilor de risc a explicat aproape jumtate din modificarea ratei evenimentelor la brbai i, ntr-o msur
mai mic, la femei.
Mai mult, a existat o asociere semnificativ ntre modificrile tratamentului i rata de deces. Prin urmare,
s-a concluzionat c att prevenia primar, ct i tratamentul evenimentelor cardiovasculare influeneaz
mortalitatea. n multe dintre centrele unde s-a desfurat studiul MONICA s-au nregistrat variaii substaniale, cretere sau descretere, a evenimentelor datorate
BCV pe perioade mai mici de 10 ani. Singura explicaie
rezonabil este c att schimbrile de mediu, n special
legate de stilul de via, ct i mbuntirea tratamentului, sunt importante.

Vol. 24, No. 4, 2014
O alt abordare n nelegerea modificrilor n mortalitatea i incidena BCV o reprezint aplicarea unor
modele precum modelul de mortalitate IMPACT29. Pe
baza informaiilor despre modificarea factorilor de risc
coronarian i a tratamentului, obinute din rezultatele
RCT (studiilor clinice randomizate) privind eficacitatea
diverselor metode de tratament, acesta estimeaz influena ateptat asupra mortalitii prin BCV n funcie
de sex i vrst. Acest model a fost aplicat n diverse
ri; rezultatele acestor studii sunt destul de concordante i similare cu ceea ce s-a observat n alte studii pe
aceeai tem, dup cum ilustreaz Figura 1. Reducerea
benefic a factorilor de risc majori mai ales fumatul,
HTA, i colesterolul a fost responsabil pentru mai
bine de jumtate din scderea deceselor prin BCV, dei
au fost contracarate de creterea prevalenei obezitii
i a diabetului de tip 2; 40% din scderea ratei de deces prin BCV se datoreaz unor tratamente mai bune
pentru infarctul miocardic acut, insuficiena cardiac,
i celelalte afeciuni cardiace. Rezultatele studiilor clinice i ale experimentelor naturale arat, de asemenea, c
o scdere a mortalitii prin BCV poate fi nregistrat
rapid dup modificri la nivel individual sau populaional ale dietei sau statusului de fumtor30.
Potenialul pe care l au pentru prevenie un stil de
via sntos, managementul corespunztor al factorilor clasici de risc i utilizarea selectiv a medicamentelor cardioprotectoare este evident. Argumentele umane
i economice n favoarea preveniei BCV au fost estimate recent de ctre Institutul Naional pentru Sntate
i Excelen Clinic (NICE)32 ca fiind extrem de pozitive, i numeroase comitete din alte ri au aproape aceeai viziune33. Conform raportului NICE, implementarea strategiei populaionale ar putea aduce numeroase
beneficii i economii:
Reducerea inegalitilor din sntate.
Reducerea costurilor prin numrul de evenimente cardiovasculare evitate.
Figura 1. Procentul scderii deceselor datorate bolii coronariene atribuite

tratamentului i modificrilor factorilor de risc n diverse populaii (adaptat dup Di Chira et al.31).

Vol. 24, No. 4, 2014
Prevenirea unor alte afeciuni precum cancerul,

bolile pulmonare, i diabetul zaharat tip 2.
Reducerea costurilor asociate cu bolile cardiovasculare, cum ar fi cele legate de medicaie, prezentrile n urgen i consulturile ambulatorii.
Reducerea costurilor n general n economie prin
scderea pierderilor legate de scderea produciei datorat mbolnvirilor la persoanele active,
scderea plilor compensatorii, i scderea costurilor datorate pensionrilor premature prin
mbolnvire.
mbuntirea calitii vieii i prelungirea vieii.
2.4 Numeroase posibiliti de ameliorare

n cadrul programului comprehensiv de prevenie al
BCV al ESC sunt realizate studii pentru a se documenta
ct de bine sunt implementate ghidurile n practica clinic. Aceste studii se numesc EUROASPIRE; rezultatele din braul pacienilor spitalizai din EUROASPIRE
III33 (2006-2007), care cuprinde 8966 pacieni cu BCV
manifest din 22 de ri europene, au artat c o mare
parte dintre pacieni nu ating intele stabilite n 2003 de
al treilea JTF, n ceea ce privete stilul de via, nivelul
factorilor de risc i intele terapeutice. Proporia pacienilor care atinseser intele privind diferite recomandri i managementul factorilor de risc este prezentat
n Tabelul 4; ideal ar fi ca 100% dintre pacieni s ating
intele, dar n practic acest lucru se ntmpl n mai
puin de jumtate din cazuri.
Mai mult, schimbrile nregistrate ntre EUROASPIRE I (1996) i EUROASPIRE III relev faptul c
proporia fumtorilor nu s-a modificat, iar controlul
TA nu s-a ameliorat, n ciuda unei creteri a utilizrii
medicamentelor antihipertensive, n timp ce numrul
pacienilor cu obezitate (central) continu s creasc.
Pe de alt parte, controlul dislipidemiilor s-a ameliorat
semnificativ5. n EUROASPIRE III, indivizii asimptomatici cu risc nalt au fost inclui n grupul de prevenie primar; aderena la recomandrile privind stilul de
via i proporia celor care atinseser intele privind
TA, nivelul lipidelor serice i glicemia a fost i mai redus34.
Aceste rezultate subliniaz necesitatea unor programe extinse i multidisciplinare care s-i implice i pe
pacieni i familiile lor. Eficacitatea i sigurana unor
asemenea programe a fost demonstrat de proiectul
EUROACTION un proiect demonstrativ al ESC care
arat c recomandrile privind modificarea stilului de
via i managementul factorilor de risc pot fi atinse i
susinute n practica clinic, att la nivelul asistenei
primare, ct i a celei secundare35.

Ce rmne incert
nelegerea noastr asupra motivelor modificrilor de comportament, la nivelul individual, ct i
la nivel populaional, este incomplet
Mecanismele prin care asemenea modificri ale
comportamentului se regsesc n modificri ale
tiparului bolii sunt de asemenea incomplet nelese.
Verificarea i studierea celor mai eficiente msuri
de prevenie reprezint prin urmare o provocare.
Este nevoie de mai multe cercetri n domeniul
preveniei cardiovasculare, ncepnd cu vrste
foarte mici sau chiar n timpul vieii intrauterine.
Nu se tie cu certitudine dac aparia BCV este
doar amnat prin msurile preventive sau dac
poate fi evitat complet.
Este nevoie n continuare de o descriere valid i
exact a morbiditii i mortalitii cardiovasculare la nivel mondial.
3. CINE AR TREBUI S BENEFICIEZE?

3.1 Strategii i estimarea riscului
Mesaje cheie*
*Diagramele SCORE detaliate cu valorile HDL-colesterol integrate pot fi gsite la adresa http://www.
escardio.org/guidelines-surveys/escguidelines/Pages/
cvd-prevention.aspx n seciunea de materiale suplimentare.
La persoanele aparent sntoase, riscul cardiovascular este cel mai frecvent rezultanta interaciunii a multipli factori de risc.
Estimarea riscului printr-un sistem de tipul diagramelor SCORE poate ajuta la formularea unor
decizii logice privind managementul pacientului
i astfel se poate evita tratamentul excesiv sau
dimpotriv, incomplet.
Anumite persoane sunt la risc cardiovascular nalt fr a fi necesar utilizarea scorurilor de risc
i necesit intervenii terapeutice imediate pentru controlul tuturor factorilor de risc.
La subiecii tineri, un risc absolut sczut poate
masca un risc relativ foarte nalt i astfel, utilizarea diagramelor de calcul a riscului relativ sau
calcularea ,,riscului conform vrstei ar putea
reprezenta instrumente utile n consilierea acestora privind necesitatea eforturilor intensive de
schimbare a stilului de via.
n timp ce femeile par a prezenta un risc cardiovascular mai mic dect al brbailor, acest aspect
ar putea induce n eroare, deoarece riscul este
mai degrab amnat cu 10 ani i nu evitat

Toate sistemele de calcul a riscului sunt relativ

brute i, de aceea, necesit atenie n utilizarea
acestora.
Factorii suplimentari care influeneaz riscul
pot fi introdui n sisteme electronice de estimare a riscului ca de exemplu HeartScore (www.
heartscore.org).
Abordarea riscului cardiovascular total este
flexibil: dac nu este posibil optimizarea unui
factor de risc, riscul total poate fi, totui, redus
prin controlul mai strns al altor factori de risc.
3.1.1 Introducere
ncurajarea utilizrii estimrii riscului total drept instrument crucial pentru a ghida managementul pacientului a reprezentat o trstur de referin a ghidurilor
nc de la prima ediie38. Aceasta se datoreaz faptului
c medicii trateaz persoana (i nu factorii de risc individuali), a crei risc cardiovascular reflect de obicei
efectele combinate a mai multor factori de risc care pot
interaciona, uneori multiplicat. Avnd n vedere acest
fapt, implicarea estimrii riscului cardiovascular total,
n mod logic, este asociat cu mbuntirea rezultatelor clinice comparativ cu alte strategii care nu au fost
testate adecvat. Dei clinicienii solicit adesea valoarea prag la care s declaneze o intervenie terapeutic,
acest lucru este problematic deoarece riscul reprezint
un continuum i nu exist un punct exact de la care,
spre exemplu, un medicament este indicat n mod automat, sau sub care consilierea privind stilul de via
ar putea s nu fie util. Acest aspect este dezbtut n
detaliu n aceste ghiduri, aa cum este i problema cu
subiecii tineri cu risc absolut sczut, dar cu risc relativ
nalt, precum i faptul c toate persoanele vrstnice ar
putea avea un risc crescut de deces i ar putea fi supraexpuse la tratamente medicamentoase.
Tabelul 4. Recomandrile ghidurilor vs. rezultatele obinute la pacienii
cu boal coronarian manifest n EUROASPIRE III
Recomandarea ghirurilor
Proporia celor care au atins inta
Oprirea fumatului
48
Exerciiu fizic regulat
34
IMC sub 25 kg/m2
18
Circumferina taliei
<94 cm (brbai)
25
<80 cm (femei)
12
Tensiunea arterial <149/90 mmHg
50
Colesterol total <175 mg/dl (4,5 mmol/L)
49
LDL colesterol <100 mg/dl (2,5 mmol/L)
55
La pacienii cu diabet zaharat tip 2:
Glicemia jeun <125 mg/dl ( 7 mmol/L)
27
HbA1c <6,5%
35
IMC=indice de mas corporal; HbA1c=hemoglobin glicozilat; LDL=lipoproteine cu densitate
mic.

Vol. 24, No. 4, 2014
Prioritile sugerate n aceast seciune vin pentru a

ajuta medicul n tratamentul individual al pacientului.
Astfel, se cunoate faptul c persoanele cu cel mai nalt
nivel al riscului obin cele mai multe beneficii din managementul factorilor de risc. ns, aa dup cum este
notat n alt parte, majoritatea deceselor ntr-o comunitate provin din rndul subiecilor cu risc sczut, pentru simplul motiv c acetia sunt mai numeroi19.
3.1.2 Strategii
Riscul cardiovascular, aa cum este descris n aceste
ghiduri, nseamn probabilitatea ca un subiect s dezvolte un eveniment cardiovascular aterosclerotic ntr-o
perioad de timp definit.
Riscul total implic o estimare n funcie de efectele factorilor de risc majori: vrsta, sexul, fumatul, tensiunea arterial i nivelul lipidelor serice. Termenul este
utilizat pe scar larg; cu toate acestea, riscul total nu
este comprehensiv deoarece efectul altor factori de risc
nu este considerat, cu excepia situaiilor eligibile.
Importana estimrii riscului total anterior lurii deciziilor terapeutice este ilustrat n Tabelul 5 i Figura
2. Figura arat faptul c efectul nivelului lipidelor asupra riscului este modest la femei, care de altfel prezint risc sczut, i, c avantajul este pierdut dac acestea
prezint combinaia: fumtoare i cu hipertensiune arterial moderat. Tabelul 5 arat c o persoan cu o valoare a colesterolului de 8 mmol/L (310 mg/dL) poate
prezenta un risc de 10 ori mai redus fa de un subiect
cu un colesterol de 5 mmol/L (190 mg/dL), dac acesta
din urm este brbat, hipertensiv i fumtor. Trialurile
clinice randomizate privind un singur factor de risc nu
ofer suficiente date pentru a aborda n totalitate aceste
aspecte. n timp ce studii ca EUROASPIRE538,39, sugereaz managementul inadecvat al factorilor de risc la
pacienii cu risc foarte nalt, este de asemenea, probabil
ca, n cazul subiecilor cu risc sczut, care nu au prezentat un eveniment vascular, s existe o utilizare excesiv a medicaiei, consecina extrapolrii inadecvate a
Recomandri privind estimarea riscului
Recomandri
Clasaa
Estimarea riscului total utiliznd mai muli factori
de risc (ca de exemplu SCORE) este recomandat
I
pentru adulii asimptomatici fr eviden de BCV
Subiecii cu risc nalt pot fi identificai prin
prezena BCV, a diabetului zaharat, a bolii renale
moderate sau severe, a unui nivel foarte nalt
I
a factorilor de risc individuali sau a unui risc
SCORE nalt i reprezint o prioritate nalt pentru
controlul intensiv privind toi factorii de risc.
Clasa de recomandri
Nivelul de eviden
c
Referine
a
b
Nivelb
GRADE
Refc
Puternic
36
Puternic
36,37

Vol. 24, No. 4, 2014
rezultatelor trialurilor care includ predominant brbai

cu risc foarte nalt la indivizii cu risc sczut.
n general, femeile, subiecii vrstnici i tinerii sunt
slab reprezentai n trialurile clasice cu medicaie conform cu ghidurile actuale.
Este esenial pentru clinicieni s fie capabili s evalueze rapid riscul i cu suficient acuratee astfel nct
s le permit luarea unor decizii logice privind managementul pacienilor. Aceasta a condus la realizarea
diagramei privind riscul utilizat n ghidurile din anii
1994 i 199838,40. Aceast diagram, derivat dintr-un
concept de pionierat dzvoltat de ctre Anderson et
al.41, utiliza parametrii vrst, sex, statusul de fumtor,
colesterolul total i tensiunea arterial sistolic (TAS)
pentru a estima riscul dezvoltrii la 10 ani a unui prim
eveniment cardiovascular fatal sau nonfatal. Au existat
cteva probleme cu aceste diagram, subliniate n al patrulea ghid JTF de prevenie37, care au condus la sistemul actual recomandat de estimare a riscului, SCORE.
3.1.3 Estimarea riscului
Cnd evaluez riscul total? Aa cum s-a subliniat n
seciunea prioriti, subiecii cu BCV diagnosticat se
afl deja la un risc foarte nalt de evenimente ulterioare i necesit controlul prompt al tuturor factorilor de
risc, n timp ce la persoanele aparent sntoase riscul
total trebuie estimat utiliznd sistemul SCORE.
Dei la modul ideal toi adulii ar trebui evaluai pentru determinarea riscului de BCV, acest lucru ar putea
s nu fie posibil pentru multe societi. Aceast decizie trebuie luat de fiecare ar, depinznd de resursele
existente. Este recomandat ca screeningul factorilor de
risc, incluznd profilul lipidic, s fie luat n discuie la
brbaii cu vrsta >40 ani i la femeile cu vrsta >50 ani
sau post-menopauz42.
Majoritatea subiecilor se prezint la medicul de familie cel puin o dat la 2 ani, oferind astfel posibilitatea de evaluare a riscului. Bazele de date provenind din
Figura 2. Relaia ntre raportul colesterol total (CT)/ HDL-colesterol i

evenimentele cardiovasculare fatale la 10 ani, la subieci de sex masculin i
feminin, n vrst de 60 ani, cu sau fr factori de risc, pe baza unei funcii
de calculare a riscului derivat din proiectul SCORE.

medicina primar ar putea fi utile pentru a stoca datele

privind factorii de risc i a identifica persoanele la risc
nalt. Se recomand ca estimarea riscului total s fie
efectuat n cadrul unei consultaii dac:
Subiectul solicit acest lucru.
Sunt cunoscui/prezeni unul sau mai muli factori de risc ca fumatul, obezitatea/supraponderea sau hiperlipemia.
Exist antecedente familiale de BCV prematur
sau de prezen a unor factori de risc majori ca
hiperlipemia.
Exist simptome sugestive pentru boli cardiovasculare.
Eforturi suplimentare trebuie fcute pentru estimarea riscului la subieci defavorizai social care sunt mai
susceptibile s prezint un cumul de factori de risc43.
Ghidul din 200344 a utilizat diagrama SCORE pentru
estimarea riscului45, sistem bazat pe datele provenite
din 12 studii europene de cohort, care au inclus 205
178 de subieci examinai iniial ntre anii 1970 i 1988,
cu 2,7 milioane ani de urmrire i 7934 decese de cauz
cardiovascular. Sistemul de evaluare a riscului SCORE
a fost validat extern46.
Diagramele de estimare a riscului, cum este SCORE,
sunt concepute n scopul facilitrii evalurii riscului
unor persoane aparent sntoase. Pacienii care au avut
un eveniment clinic, cum ar fi un sindrom coronarian
acut (SCA) sau a un accident vascular cerebral (AVC)
se calific automat pentru evaluarea i managementul
intensiv al factorilor de risc.
SCORE difer de sistemele anterioare de estimare a
riscului prin mai multe elemente importante i a fost
modificat ntr-o oarecare msur pentru acest ghid.
Detalii privind aceste modificri, n cele ce urmeaz.
Sistemul SCORE estimeaz riscul de apariie a unui
prim eveniment aterosclerotic fatal la 10 ani, indiferent
dac este vorba de un infarct miocardic, AVC, anevrism de aort sau altele. Sunt incluse toate codurile
din Clasificarea Internaional a Bolilor (International
Classification of Diseases, ICD) l care, n mod rezonabil,
se presupune c sunt determinate ateroscleroz. Multe
ale sisteme estmeaz doar riscul de boal coronarian.
Tabelul 5. Impactul asocierii factorilor de risc n grila SCORE de apreciere a riscului la 10 ani de boal cardiovascular fatal
Colesterol
Sex
Vrsta (ani)
TA (mmHg)
Fumat
Risc (%)
(mol/l)
F
60
8
120
Nu
2
F
60
7
140
Da
5
M
60
6
160
Nu
8
M
60
5
180
Da
21

Alegerea mortalitii prin BCV, n detrimentul evenimentelor totale (fatale + non-fatale), a fost intenionat, dei nu este larg acceptat. Ratele evenimentelor
non-fatale sunt dependente n mod critic de definiia
aleas i de metodele utilizate pentru confirmarea lor.
De cnd s-au desfurat studiile de cohort care au stat
la baza alctuirii sistemului SCORE au survenit modificri importante ale testelor diagnostice i ale metodelor
terapeutice. Este esenial faptul c utilizarea mortalitii
permite recalibrarea pentru a lua n considerare modificrile n timp ale mortalitii prin BCV. Orice sistem
de estimare a riscului va supraevalua riscul n rile n
care mortalitatea a sczut i va subevalua riscul n rile n care mortalitatea a crescut. Dac sunt disponibile
date actualizate asupra mortalitii i a prevalenei factorilor de risc, poate fi realizat o recalibrare care s ia
n considerare modificrile temporale. Calitatea datelor
nu permite acest lucru pentru evenimentele non-fatale.
Din aceste motive, au fost realizate diagrame ale mortalitii prin BCV, care au fost recalibrate ntr-un numr
de ri europene. Sunt disponibile versiuni calibrate
specifice pentru Cipru, Republica Ceh, Germania,
Grecia, Polonia, Slovacia, Spania i Suedia i versiuni
specifice pentru Bosnia i Heregovina, Croaia, Estonia, Frana, Romnia, Federaia Rus i Turcia, disponibile pe www.heartscore.org. n orice caz, esenial este
estimarea riscului total.
n ghidul din 200344, un risc de deces prin BCV 5%
la 10 ani a fost considerat, n mod arbitrar, risc nalt.
Chiar dac acesta implic o ans de 95% de a nu deceda
prin BCV n decurs de 10 ani, faptul este puin impresionant pentru pacient n procesul de consiliere. Noua
nomenclatur utilizat n ghidul din 2007 preciza c
orice persoan cu risc de deces prin BCV 5% la 10 ani
prezint risc crescut. Desigur c riscul de evenimente
totale, fatale i non-fatale, este mai mare, iar clinicienii
doresc cuantificarea acestuia. Cea mai mare contribuie
la diagrama SCORE pentru riscul nalt a venit din contribuia finlandez pentru MONICA, FINRISK, avnd
date despre evenimentele nonfatale, definite conform
proiectului MONICA47. Calcularea ratelor evenimentelor totale din FINRISK sugereaz faptul c, la nivelul
(5%) la care ar trebui ntrit consilierea asupra riscului, riscul total de evenimente cardiovasculare este de
aproximativ 15%. Aceast multiplicare de trei ori a riscului este ceva mai mic la subiecii vrstnici, la care un
prim eveniment cardiovascular este mult mai probabil
s fie fatal. O examinare a datelor Framingham privind
estimarea riscului total de evenimente cardiovasculare determin concluzii similare: un risc SCORE de 5%

Vol. 24, No. 4, 2014
de evenimente cardiovasculare fatale echivaleaz cu un

risc total de BCV Framingham de 10-25%, depinznd
de funcia din Framingham aleas. i de aceast dat
valoarea inferioar a intervalului se aplic persoanelor
vrstnice.
n rezumat, motivele pentru a reine un sistem care
estimeaz BCV fatale comparativ cu nsumarea BCV
fatale + non-fatale sunt:
Decesul reprezint un end-point cu greutate i
reproductibil; un eveniment non-fatal este variabil i depinde de definiie, criteriile de diagnostic i testele diagnostice, toate acestea putnd
varia n timp. De aceea riscul de 20% din totalul
BCV (sau boala coronarian) utilizat de multiple ghiduri pentru a desemna riscul nalt, este
probabil s fie variabil, instabil n timp i dificil
de validat.
Un risc nalt de deces prin BCV indic automat
un risc nalt de evenimente totale.
Multiplicatorul utilizat pentru a converti BCV
fatale la BCV totale este la fel de instabil i este
adesea sub ateptrile clinicienilor, avnd n vedere c perioada de urmrire se ncheie n toate
sistemele actuale cu apariia unui prim eveniment, iar evenimentele fatale sau nonfatale ulterioare nu sunt luate n considerare.
Utilizarea BCV fatale, drept criteriu, permite recalibrarea cu acuratee la alte ri i culturi pentru variaia n timp a mortalitii i a prevalenei
factorilor de risc, un aspect important avnd n
vedere diversitatea cultural din Europa.
Aa cum s-a menionat n introducere, a determina
praguri de la care s nceap o anumit intervenie este
problematic, riscul fiind un continuum i neavnd o
valoare prag de la care, de exemplu, s fie indicat automat un medicament. O problem particular este
reprezentat de persoanele tinere cu niveluri nalte ale
factorilor de risc un risc absolut mic poate ascunde
un risc relativ nalt, necesitnd iniierea msurilor intensive de schimbare a stilului de via. n Ghidul din
200344, a fost sugerat extrapolarea riscului la cel al unei
persoane de 60 de ani, pentru a accentua faptul c, n
absena msurilor preventive, riscul absolut va fi nalt.
Aceast parte a textului a fost reformulat, iar la diagramele de estimare a riscului absolut, a fost adugat o diagram pentru riscul relativ, pentru a ilustra faptul c,
n special la persoanele tinere, modificrile stilului de
via pot reduce n mod substanial riscul i pot reduce
creterea riscului ce va surveni odat cu naintarea n

Vol. 24, No. 4, 2014
vrst. O nou abordare a acestei probleme n aceste

ghiduri este a riscului cardiovascular legat de vrst
(cardiovascular risk age), dezvoltat ulterior n aceast
seciune.
O alt problem este legat de persoanele vrstnice.
Pentru anumite categorii de vrst, marea majoritate a
subiecilor, n special de sex masculin, va avea un risc
estimat de deces prin BCV peste pragul de 5-10%, numai pe baza vrstei (i sexului), chiar i atunci cnd ali
factori de risc pentru BCV au niveluri relativ reduse.
Aceasta ar putea conduce la utilizarea excesiv a medicamentelor la persoanele vrstnice. Aceast problem
este tratat ulterior n acest seciune.
Rolul lipoproteinelor cu densitate nalt (HDL) n
estimarea riscului a fost reexaminat sistematic utiliznd bazele de date SCORE48,49. Aceste cercetri au
artat c HDL colesterolul poate contribui substanial
la estimarea riscului dac este introdus ca variabil independent. De exemplu, HDL colesterolul modific
riscul la toate nivelurile de risc conform estimrilor
din diagramele SCORE care includ colesterolul50. Mai
mult, acest efect este observat la ambele sexe i la toate
grupele de vrst, inclusiv la femeile vrstnice51. Acest
aspect este deosebit de important la niveluri de risc
chiar sub pragul pentru iniierea msurilor intensive de
modificare a riscului de 5%. Muli dintre aceti subieci
vor necesita recomandri privind msuri intensive de
schimbare a stilului de via dac prezint valori sczute ale HDL colesterol50. Versiunea electronic, interactiv a SCOREHeartScore (disponibil la adresa
www.heartscore.org) este n prezent adaptat pentru a
permite ajustarea privind impactul HDL colesterolului
asupra riscului total.
Rolul valorilor crescute ale trigliceridelor plasmatice
drept predictor pentru BCV este dezbtut de muli ani.
Trigliceridele jeun influeneaz riscul n analiza univariat, dar efectul este atenuat de ajustarea pentru ali
factori de risc, n special HDL colesterol. Dup ajustarea pentru HDL colesterol, nu se constat asociere
semnificativ statistic ntre trigliceride i BCV52. Recent, atenia s-a concentrat pe trigliceridele determinate n cursul zilei i nu jeun, care pot prezenta corelaii
mai strnse cu riscul cardiovascular, independent de
efectele HDL colesterol53-55.
Frecvena cardiac s-a demonstrat a fi un factor de
risc independent pentru BCV n populaia general56,57.
Moartea subit cardiac a fost asociat, n mod special,
cu valorile crescute, n repaus, ale frecvenei cardiace57.
Msurarea frecvenei cardiace de repaus ar trebui realizat n poziie eznd dup 5 minute de repaus i ar

trebui s constituie parte din examenul fizic de rutin,

atunci cnd se evalueaz riscul cardiovascular.
Dou studii observaionale mari au artat creterea
riscului de evenimente cardiovasculare la subiecii la
care frecvena cardiac de repaus crete n timp58,59.
Cu toate acestea relaia invers a fost evideniat doar
n unul din aceste studii; i anume c subiecii la care
frecvena cardiac scade n timp au un risc mai mic de
dezvoltare a BCV. Pn n prezent nu avem nici un trial care s demonstreze c scderea frecvenei cardiace
poate contribui la prevenia BCV la subiecii sntoi;
de aceea, scderea prin mijloace farmacologice a frecvenei cardiace nu poate fi recomandat n prevenia
primar. Frecvena cardiac crescut s-a demonstrat a
fi asociat cu creterea riscului de evenimente cardiace
ulterioare la subiecii cu BCV cunoscut60,61. La pacienii cu un infarct miocardic i la subiecii cu insuficien
cardiac, utilizarea beta-blocantelor n doze titrate cu
atenie, este asociat cu ameliorarea prognosticului62,63.
Studii mai noi, la pacienii cu frecven cardiac de repaus 70 bti/minut i cu funcie ventricular stng sczut (fie consecina bolii coronariene, fie a insuficienei cardiace), au artat beneficii prin scderea
frecvenei cardiace64,65. Nu exist, la momentul actual,
suficiente dovezi pentru a recomanda o valoare int
pentru frecvena cardiac.
Luarea n considerare a impactului unor factori de
risc adiionali, cum sunt HDL colesterolul, greutatea
corporal, istoricul familial i noii markeri ai riscului, este dificil de realizat pentru varianta tiprit a
diagramei. Versiunea electronic, interactiv a SCORE HeartScore - este mai puin limitativ. n prezent,
aceasta reprezint o copie n format electronic a SCORE, dar va fi utilizat pentru includerea rezultatelor
noilor analize SCORE, cum sunt cele legate de HDL
colesterol, pe msura verificrii i validrii acestora.
Totui, trebuie menionat faptul c, dei au fost identificai muli ali factori de risc [cum sunt valorile proteinei C reactive (CRP) i ale homocisteinei] pe lng
cei puini inclui n funciile disponibile de evaluare
a riscului, contribuia lor la estimarea riscului absolut
pentru BCV la pacieni (alaturi de factorii de risc clasici) este, n general, modest66.
A fost reexaminat impactul diabetului zaharat autoraportat. Chiar dac cohortele sunt heterogene, impactul diabetului zaharat asupra riscului apare fie mai
mare dect n sistemele de estimare a riscului bazate pe
cohorta de la Framingham, riscul relativ fiind de aproximativ 5 pentru femei i 3 pentru brbai.
Unele dintre avantajele utilizrii diagramelor de evaluare a riscului pot fi rezumate dup cum urmeaz:

Avantajele utilizrii diagramei de estimare a riscului SCORE
Instrument intuitiv, uor de utilizat
Ia n considerare natura multifactorial a BCV
Permite un management flexibil dac nu poate fi atins nivelul ideal al unui factor de risc,
riscul total poate fi totui redus prin reducerea altor factori de risc
Permite o evaluare mai obiectiv a riscului n timp
Stabilete un limbaj comun din punct de vedere al riscului pentru clinicieni
Arat cum riscul crete cu vrsta
Noua diagram pentru riscul relativ arat cum o persoan tnr cu risc absolut sczut poate
avea un risc relativ substanial mai mare i reductibil
Calcularea individual a riscului legat de vrst risk age poate fi, de asemenea, folosit n
aceast situaie.
rile cu risc nalt pentru BCV sunt toate acelea care

nu sunt listate sub diagrama pentru rile cu risc sc-

Vol. 24, No. 4, 2014
zut (Figura 4). Dintre acestea, unele sunt cu risc foarte

nalt i diagramele pentru riscul nalt ar putea subestima riscul pentru acestea. Aceste ri sunt Armenia,
Azerbaijan, Belarus, Bulgaria, Georgia, Kazakstan, Kirgizstan, Letonia, Lituania, Macedonia FYR, Moldova,
Rusia, Ucraina i Uzbekistan
Diagramele SCORE de estimare a riscului sunt reprezentate n Figurile 3-5; este inclus, de asemenea, o
diagrama a riscului relativ. Instruciunile privind utilizarea lor urmeaz.
V rugm s reinei c diagrama din Figura 5 arat
riscul relativ i nu riscul absolut. Astfel, o persoan din
Figura 3. Diagrama SCORE: riscul pe 10 ani de BCV fatal, n rile cu risc nalt de BCV, n funcie de urmtorii factori de risc: vrst, sex, fumat, tensiune
arterial sistolic i colesterol total.

Vol. 24, No. 4, 2014
caseta din dreapta sus are un risc de 12 ori mai mare

dect o persoan din stnga jos. Acest aspect ar putea fi
util atunci cnd oferii recomandri privind necesitatea
schimbrii stilului de via unui tnr cu un risc absolut sczut, dar cu risc relativ nalt.
rile cu risc sczut pentru BCV sunt Andora, Austria, Belgia, Cipru, Danemarca, Finlanda, Frana, Germania, Grecia, Islanda, Irlanda, Israel, Italia, Luxemburg, Malta, Monaco, Olanda, Norvegia, Portugalia,
San Marino, Slovenia, Spania, Suedia, Elveia, Marea
Britanie.

Riscul vrst cardiovascular

Riscul vrst (sau vst risc sau asociat vrstei,risk
age) a unei persoane cu mai muli factori de risc cardiovascular este vrsta unei persoane cu acelai nivel
al riscului, dar cu niveluri ideale ale factorilor de risc.
Astfel un subiect de 40 de ani cu risc nalt, poate avea
o vrst risc 60 ani. Vrsta riscului reprezint un mod
intuitiv i uor de neles de a ilustra scderea speranei
de via la o persoan tnr, care prezint un risc absolut sczut, dar un risc relativ nalt pentru boli cardiovasculare, dac nu sunt adoptate msuri de prevenie.
Figura 4. Diagrama SCORE: riscul pe 10 ani de BCV fatal, pentru rile cu risc sczut de BCV, n funcie de urmtorii factori de risc: vrst, sex, fumat,
tensiune arterial sistolic i colesterol total. De notat c riscul total de evenimente cardiovasculare (fatale + non-fatale) va fi de aproximativ trei ori mai mare
dect cel din figuri.

Figura 5. Diagrama riscului relativ pentru mortalitatea la 10 ani. Conversia

colesterolului din mmol/L n mg/dL: 8 =310, 7 =270, 6 =230, 5 =190, 4 =155.
Vrsta riscului poate fi estimat vizual privind diagrama SCORE (aa cum este ilustrat n Figura 6). n
acest tabel, vrsta riscului este calculat comparativ cu
un subiect cu niveluri ideale ale factorilor de risc, considerat nefumtor, cu o valoare a colesterolului total de
4 mmol/L (155 mg/dL) i cu o tensiune arterial de 120
Figura 6. Ilustrarea conceptului vrstei riscului cardiovascular.

Vol. 24, No. 4, 2014
mmHg67. Riscul nalt este, de asemenea, calculat automat ca parte a ultimei versiuni a HeartScore (www.
HeartScore.org).
Vrsta riscului s-a demonstrat a fi independent de
end-point-ul cardiovascular utilizat67, astfel rezolvndu-se dilema alegerii ntre sistemul de estimare bazat
pe mortalitatea prin BCV i cel care estimeaz toate
evenimentelor cardiovasculare, acesta din urm fiind
mai atractiv, dar cu end-point criticabil. Vrsta riscului poate fi utilizat n orice populaie indiferent de valoarea iniial a riscului i de modificrile seculare n
mortalitate i, prin urmare, nu necesit recalibrare.68
n prezent, vrsta riscului este recomandat pentru a
ajuta clinicienii s comunice pacienilor despre riscul
individual, n special subiecilor tineri cu un risc absolut sczut, dar cu un risc relativ nalt. La momentul
actual nu se recomand ca deciziile terapeutice s se
bazeze pe vrsta riscului.


Vol. 24, No. 4, 2014
Care sunt rile cu risc sczut? (rile din Figura 4)

Faptul c mortalitatea prin BCV a sczut n multe
ri din Europa semnific faptul c multe ri au trecut
n categoria de risc sczut. n timp ce orice valoare limit este arbitrar i supus dezbaterii, n aceste ghiduri
valorile limit sunt bazate pe mortalitatea prin BCV i
diabet zaharat corespunztoare anului 2008, la subiecii cu vrste cuprinse n intervalul 45-74 ani (220/100
000 pentru sexul masculin i 160/100 000 pentru sexul
feminin)69. Aceast limit corespunde pentru 21 de ri
i marcheaz un punct la care exist un decalaj semnificativ anterior celei de a 22-a ar (Republica Ceh).
Lista este bazat pe rile Europei care sunt membre
ale ESC. Cu toate acestea, cteva ri europene nu sunt
membre ESC deoarece nu dein societi naionale de
cardiologie sau datorit dimensiunilor rilor respective. n plus, JTF a considerat rezonabil s includ i ri
care sunt membre ESC, dar nu sunt considerate strict
Europene n terminologia OMS.
rile cu risc foarte nalt

Unele ri europene prezint niveluri ale riscului
care sunt mai mult dect duble fa de mortalitatea prin
BCV de 220/100 000 la sexul masculin, atribuit prin
definiie rilor cu risc sczut. Raportul brbai:femei
este mai mic la acestea comparativ cu rile cu risc sczut, sugernd o problem major privind sexul feminin. Chiar i diagramele pentru risc nalt pot subestima riscul n aceste ri. rile cu un risc de mortalitate
prin BCV >500/100 000 pentru brbai i >250/100 000
pentru femei reprezint ri cu risc foarte nalt i sunt
enumerate n Figura 3. Toate rile care rmn sunt ri
cu risc nalt.
Cum se utilizeaz diagramele de evaluare a riscului
Utilizarea diagramelor corespunztoare riscului
sczut este recomandat pentru rile enumerate
n Figura 4. Utilizarea diagramelor corespunztoare riscului nalt este recomandat pentru
toate celelalte ri europene i mediteraneene. De
reinut c mai multe ri au realizat re-calibrri
la nivel naional pentru a actualiza distribuia
factorilor de risc i a identifica tendinele n timp
ale mortalitii. Aceste diagrame sunt ar putea
reprezenta mai bine nivelurile riscului actual.
Pentru a estima riscul de deces prin BCV la 10
ani al unui subiect, identificai csua corect
pentru sexul persoanei respective, pentru statusul de fumtor i pentru vrsta acestuia. n cadrul
csuei identificai csua cea mai apropiat de
valoarea tensiunii arteriale i a colesterolului to-
tal sau a raportului colesterol total: HDL colesterol a persoanei respective. Riscul estimat va
trebui s fie ajustat la un nivel superior atunci
cnd persoana se apropie de urmtoarea categorie de vrst.
Persoanelor care prezint risc sczut li se vor
oferi recomandri pentru meninerea riscului la
acest nivel. Deoarece nu exist o valoare limit
universal aplicabil, intensitatea recomandrilor
ar trebui s creasc simultan cu creterea riscului. n general, pentru subiecii cu un risc de
deces prin BCV 5% sunt necesare recomandri
intensive i, acetia, ar putea beneficia de tratament medicamentos. La un nivel al riscului
>10%, tratamentul farmacologic este necesar
mult mai frecvent. La subiecii cu vrsta >60 ani,
aceste valori prag ar trebui interpretate mai cu
ngduin, deoarece la acetia riscul specific
vrstei este n mod obinuit n jurul acestor niveluri, chiar i atunci cnd ali factori de risc cardiovascular prezint valori normale.
Diagramele privind riscul relativ pot fi utile n
identificarea i consilierea subiecilor tineri, chiar dac la acetia, riscul absolut este sczut.
Diagramele pot fi utilizate pentru a oferi nite
indicaii cu privire la efectele reducerii factorilor
de risc, dat fiind faptul c va exista un decalaj de
timp anterior reducerii riscului, iar rezultatele
studiilor clinice randomizate ofer estimri mai
bune ale beneficiilor. Subiecii care opresc fumatul, n general, i reduc riscul la jumtate.
Calificative
Diagramele pot ajuta la evaluarea i managementul riscului, dar trebuie utilizate n lumina cunotinelor i raionamentului clinicianului, n
special n contextul condiiilor locale.
Riscul va fi supraevaluat n rile n care rata de
mortalitate prin BCV este n scdere i va fi subevaluat n rile n care aceasta este n cretere.
La orice vrst, riscul pare s fie mai mic pentru
femei dect pentru brbai. Analiza diagramelor
arat c riscul este doar amnat n cazul femeilor,
astfel c o persoan de sex feminin cu vrsta de
60 ani prezint un risc asemntor cu un brbat
de 50 de ani.
Riscul poate fi mai mare dect cel indicat de diagram
la:
Subiecii sedentari sau cei cu obezitate central;

aceste caracteristici influeneaz multe dintre aspectele riscului, enumerate mai jos. Riscul cres

cut asociat cu excesul ponderal este mai mare la

pacienii mai tineri comparativ cu subieci mai
vrstnici.
Persoanele defavorizate social i cele din minoritile etnice.
Subiecii cu diabet zaharat: diagramele SCORE
ar trebui utilizate doar n cazul persoanelor cu
diabet zaharat de tip 1 fr leziuni ale organelor
int. Riscul crete odat cu creterea valorilor
glicemiei, chiar anterior instalrii diabetului.
Subiecii cu valori reduse ale HDL colesterolului,
cu valori crescute ale trigliceridelor, fibrinogenului, apolipoproteinei B (apoB) i lipoproteinei(a)
[Lp(a)], n special n combinaie cu hipercolesterolemia familial i probabil cu creterea proteinei C nalt sensibile (hsCRP). n particular,
un nivel sczut al HDL colesterolului va indica
un risc nalt la ambele sexe, la toate grupele de
vrst i la toate nivelurile de risc51.
Subiecii asimptomatici cu dovezi de ateroscleroz preclinic, de exemplu cu plac de aterom
evideniat la ecografia carotidian.
Subiecii cu insuficien renal cronic moderat
spre sever [rata filtrrii glomerulare (RFG) <60
mL/min/1,73 m2].
Subiecii cu istoric familial de BCV prematur.
Prioriti
Cu ct este mai nalt riscul cu att mai mari sunt beneficiile care rezult din eforturile de prevenie, ceea ce
duce la urmtoarele prioriti:
1. Risc foarte nalt
Subiecii cu oricare din urmtoarele elemente:
BCV documentat prin teste invazive sau noninvazive (ca angiografia coronarian, rezonana
magnetic nuclear, ecocardiografia de stres, evidenierea plcii de aterom carotidiene la ecografie), antecedente de infarct miocardic, sindrom
coronarian acut, revascularizare coronarian
(PCI, CABG) i alte proceduri de revascularizare arterial, accident vascular cerebral ischemic,
boal arterial periferic .
Diabet zaharat (tip 1 sau tip 2) cu unul sau mai
muli factori de risc cardiovasculari i/sau cu
leziuni ale organelor int (ca de exemplu microalbuminuria: 30-300 mg/24 h).
Boal cronic de rinichi sever (RFG <30 mL/
min/1,73 m2).
Un risc SCORE calculat 10%.

Vol. 24, No. 4, 2014
2. Risc nalt
Subiecii cu oricare din urmtoarele elemente:
Un singur factor de risc cu valori extrem de ridicate, ca de exemplu dislipidemie familial sau
hipertensiune arterial sever.
Diabet zaharat (tip 1 sau tip 2), dar fr factori
de risc cardiovascular sau leziuni ale organelor
int.
Boal cronic de rinichi moderat (RFG 30-59
mL/min/1,73 m2).
Un risc SCORE calculat 5% i <10% de deces
prin BCV la 10 ani.
3. Risc moderat
Subiecii sunt considerai a prezenta risc moderat
cnd riscul lor SCORE este 1 i <5% la 10 ani. Muli
subieci de vrst medie aparin acestei categorii. Acest
risc este, mai departe, modulat de factorii menionai
anterior.
4. Risc sczut
Categoria de risc sczut se aplic subiecilor cu un
risc SCORE <1% i care nu prezint caracteristici care
ar putea s i ncadreze n categoria de risc moderat.
Aceste categorii de risc sunt compatibile cu ghidurile comune ale Societii Europene de Ateroscleroz/
ESC privind dislipidemiile70. Ghidurile comune ofer
recomandri suplimentare asupra tratamentului dislipidemiilor bazate pe aceste categorii de risc.
Concluzii
Estimarea riscului cardiovascular total rmne o
parte esenial a acestui ghid. Sistemul SCORE a fost
actualizat cu o estimare a riscului total de BCV, ct i
a riscului de deces prin BCV. Sunt incluse informaii
noi referitoare la diabetul zaharat. Pe lng informaiile
referitoare la riscul absolut, sunt adugate i informaii asupra riscului relativ, pentru a facilita consilierea
persoanelor tinere al cror risc absolut sczut poate ascunde un risc substanial i modificabil, legat de vrst.
Prioritile definite n acest capitol sunt pentru uz
clinic i reflect faptul c persoanele cu cel mai mare
risc de evenimente cardiovasculare au cel mai mult de
ctigat din msurile preventive. Aceast abordare ar
trebui s completeze aciunile publice care urmresc
reducerea nivelului factorilor de risc n comunitate i
promovarea unui stil de via sntos.
Principiile de evaluare a riscului i definirea prioritilor reflect ncercarea de a face problemele complexe
simple i accesibile, dar ele trebuie s fie interpretate


Vol. 24, No. 4, 2014
n lumina att a datelor detaliate privind pacientul pe

care le deine clinicianul, ct i a condiiilor i ghidurilor locale.
Lacunele rmase
Sistemul actual de clasificare a dovezilor acord
mai mult importan studiilor clinice randomizate. n timp ce acest aspect este necesar, multe
din msurile privind schimbarea stilului de via
sunt mai puin pretabile la astfel de evaluare comparativ cu tratamentele medicamentoase, acestora tinznd s li se acorde o poziie superioar din
punct de vedere a eficienei. n timp ce sistemul
GRADE ncearc s rezolve aceast problem,
mai multe studii sunt necesare .
Nu exist trialuri clinice randomizate recente
privind abordarea riscului total n ceea ce privete: (i) evaluarea riscului; sau (ii) managementul riscului.
Subiecii tineri, femeile, persoanele vrstnice i
minoritile etnice continu s fie slab reprezentate n trialurile clinice.
Este necesar o comparaie sistematic a ghidurilor internaionale actuale pentru a defini ariile
de consens, precum i motivele care genereaz
discrepane.
nu este suficient pus n aplicare. n SCORE, evaluarea

istoricului familial este probabil foarte brut i n mod
sigur subestimat. Istoricul familial reprezint o combinaie variabil ntre genetic i mediul nconjurtor.
Exist dovezi privind importana major a ereditii
pentru muli factori de risc cardiovascular.
Un numr de polimorfisme genetice (variante de
secvene genetice ce apar cu o frecven <1%) par s fie
asociate cu efecte semnificative statistic asupra riscului
la nivel populaional. Datorit determinanilor poligenici i polifactoriali ai celor mai frecvete BCV, impactul
unui singur polimorfism rmne mai curnd modest.
Testele genetice pot identifica variantele asociate cu
creterea riscului pentru factorii de risc cardiovascular
individuali, pentru boala coronarian sau pentru accidentul vascular cerebral. Sunt disponibile recent teste
comerciale pentru a prezice riscul genetic individual,
inclusiv testarea direct la consumator. Beneficiile clinice ale testelor comerciale nu au fost demonstrate pn
n prezent74.
n anumite condiii procesul de consiliere genetic
poate fi optimizat i extins prin utilizarea screeningului n cascad, care identific pacienii la risc i permite
tratamentul n timp util al rudelor afectate, ca de exemplu, n cazul hipercolesterolemiei familiale72,75.
3.3 Vrsta i sexul
Mesaje cheie
BCV reprezint, de departe, cea mai important
cauz de mortalitate la sexul feminin.
Riscul dezvoltrii BCV la femei, precum i la
brbai poate fi redus prin lipsa fumatului, activitate fizic, evitarea obezitii, controlul valorilor
tensiunii arteriale i a colesterolului seric (i a le
trata n cazul n care prezint valori crescute).
3.2 Genetica
Mesaje cheie
Importana prevalenei familiale a BCV premature nu este nc suficient neleas n practica
clinic.
Recomandri privind testarea genetic
Recomandri
Clasaa
n prezent, testele bazate pe ADN pentru
polimorfisme genetice comune nu contribuie
semnificativ la diagnosticul, predicia riscului
III
sau managementul pacientului i nu pot fi
recomandate.
Genotiparea suplimentar, ca alternativ sau
n plus fa de fenotipare, pentru un manageIII
ment mai bun al riscului i pentru prevenia
timpurie la rude, nu poate fi recomandat.
a
Clasa de recomandri
b
Nivelul de eviden
c
Referine
Nivelb
GRADE
Refc
Puternic
71
Puternic
72
Prevalena familial a bolii aterosclerotice sau a factorilor de risc major (hipertensiunea arterial, diabetul
zaharat, hiperlipidemia) ar trebui cercetat sistematic
la rudele de gradul I ale oricrui pacient care prezint
boli cardiovasculare premature, vrsta <55 ani pentru
brbai i <65 ani pentru femei73. Aceast recomandare
Recomandri privind vrsta i sexul

Recomandri
Femeile i persoanele vrstnice ar trebui incluse n
evaluarea riscului pentru BCV n acelai mod ca alte
grupuri populaionale pentru a determina necesitatea
tratamentului specific.
a
b
c
Clasaa
I
Nivelb GRADE
B
Puternic
Refc
76,77
Clasa de recomandri
Nivelul de eviden
Referine
Vrsta naintat i sexul masculin cresc riscul pentru

BCV i reprezint caracteristici fixe utilizate pentru a
stratifica riscul45.
A fost susinut utilizarea vrstei 55+ ca unic factor
de risc n determinarea necesitii de terapie farmacologic cu o combinaie de antihipertensive n doz
mic, de statine i de aspirin78. Totui expunerea la

factorii de risc comuni crete, de asemenea, cu vrsta,

i ntre o treime i o jumtate din diferenele n riscul
pentru BCV legate de vrst (ntre 25-49 vs. 50-59 i
60-64 ani) la populaia finlandez sunt explicate de fumat, raportul HDL:colesterol total, tensiunea arterial
sistolic, indicele de mas corporal (IMC) i diabetul
zaharat76. Ali factori de risc ca de exemplu, sedentarismul i statusul socio-economic precar pot contribui, de
asemenea, la diferenele de risc legate de vrst.
Vrsta reprezint un marker bun privind durata expunerii la factori de risc cardiovascular cunoscui sau
necunoscui. Subiecii relativ tineri prezint un risc
absolut sczut de evenimente cardiovasculare n urmtorii 10 ani, n ciuda faptului c dein o gam complet
de factori de risc. De exemplu, un brbat de 45 ani care
fumeaz, care prezint o tensiune arterial sistolic de
180 mmHg i o valoare a colesterolului plasmatic de 8
mmol/L prezint un risc de evenimente cardiovasculare fatale de doar 4% la 10 ani (conform diagramelor
SCORE), ceea ce sugereaz c nu ar fi necesar tratamentul farmacologic. Cu toate acestea, diagrama riscului relativ (Figura 5) indic faptul c acest risc este
deja de 12 ori mai mare comparativ cu al unui brbat
fr factori de risc. Cinci ani mai trziu, cnd acesta
va avea 50 ani, riscul acestuia va crete n zona periculoas de 14% la 10 ani i acesta va necesita tratament
farmacologic. Consideraii similare se aplic la femei
care prezint un risc absolut sczut la vrste tinere i
pot avea niveluri mari ale factorilor de risc specifici. n
aceste circumstane, este necesar raionamentul clinic
- scorurile de risc nu dicteaz deciziile terapeutice. Msuri adiionale, ca imagistica prin computer tomografie
pentru a obine scorurile de calciu la nivel coronarian,
ar putea fi utile79, dar adaug costuri suplimentare considerabile, precum i timp, iar beneficiile rmn nedovedite80.
BCV reprezint o cauz major de mortalitate la femeile din toate rile europene; la vrste sub 75 ani,
42% din persoanele de sex feminin decedeaz prin
BCV comparativ cu 38% din brbai14. Ratele mai mici
ale bolii coronariene la femei dar nu i a accidentului vascular cerebral pot fi interpretate prin efectul
protectiv oferit de hormonii estrogeni endogeni. Cu
toate acestea, analiza tendinelor n timp i ntre statele europene arat c aceast relaie variaz, fcnd
din aceasta o explicaie implauzibil81. Diferenele ntre
sexe n ceea ce privete aportul de grasimi alimentare
(mai degrab dect fumatul n exces la brbai) pot fi
responsabile81. Mortalitatea prin BCV nu crete la femeile la menopauz, indicnd faptul c la sexul feminin riscul este mai degrab amnat dect evitat total.

Vol. 24, No. 4, 2014
American Heart Association (AHA) a publicat o actualizare a ghidurilor privind prevenia BCV la femei82,
care subliniaz c recomandrile sunt aceleai la ambele sexe, cu cteva excepii. Utilizarea scorului Framingham este recomandat, i include, la momentul actual,
o categorie denumit sntate cardiovascular ideal
care cuprinde absena nivelurilor ridicate a factorilor
de risc, IMC <25 kg/m2, activitate fizic regulat moderat sau intensiv i o diet sntoas. n US Womens
Health Initiative, doar 4% din femei s-au ncadrat n
statusul ideal i alte 13% nu prezentau factori de risc,
dar nu au reuit s urmeze un stil de via sntos83.
S-a identificat o diferen de 18% privind evenimentele
majore cardiovasculare n favoarea stilului de via ideal vs. grupul fr factori de risc: 2,2% i respectiv 2,6%
la 10 ani.
Cele mai importante noi informaii
Femeile asimptomatice i persoanele vrstnice
beneficiaz de evaluarea riscului pentru a determina managementul optim al acestora.
Lacune rmase
Investigaiile clinice care s ajute deciziile terapeutice la persoane tinere cu un nivel nalt al factorilor de risc necesit evaluri suplimentare.
3.4. Factorii de risc psihosociali
Mesaje cheie
Statusul socioeconomic precar, lipsa suportului
social, stresul profesional i familial, depresia,
anxietatea, ostilitatea i tipul D de personalitate,
toate acestea contribuie la riscul de a dezvolta
BCV i la agravarea clinic i prognostic a BCV.
Aceti factori acioneaz drept bariere n calea
aderenei la tratament i a eforturilor de mbuntire a stilului de via, precum i a promovrii
strii de sntate i bunstare la nivel individual,
de pacient i populaional. n plus, au fost identificate mecanisme psiho-biologice distincte,
care sunt implicate direct n patogeneza BCV.
Recomandri privind factorii psihosociali
Recomandri
Clasaa
Factorii de risc psihosociali ar trebui evaluai prin
anamnez sau chestionar standardizat. Managementul
clinic adaptat la pacient ar trebui luat n considerare
IIa
pentru a mbunti calitatea vieii i prognosticul
privind BCV.
a
b
c
Clasa de recomandri
Nivelul de eviden
Referine
Nivelb GRADE
Puternic
Refc
84-86

Vol. 24, No. 4, 2014

3.4.1 Factori de risc

Statusul socio-economic precar
Multiple studii prospective au artat c femeile i
brbaii cu status socioeconomic precar, definit ca nivel
educaional sczut, cu venituri mici, care dein un loc
de munc cu statut sczut sau locuiesc ntr-o arie rezidenial srac, prezint un risc crescut de mortalitate
global, precum i prin BCV. [risc relativ (RR) ~1,32,0]87-91.
0,7). O mortalitate mare a putut fi observat doar la

pacienii cu infarct miocardic, cu funcia ventricular
stng redus postinfarct (HR 1,3), sugernd efectele
diametral opuse ale anxietii la diferite subgrupuri de
pacieni cu BCV110. Cu toate acestea, dou meta-analize recente au confirmat c anxietatea este un factor
de risc independent pentru BCV (HR 1,3)111 i pentru
evenimente adverse dup un infarct miocardic (OR 1,5
i, respectiv, 1,7)112.
Izolarea social i suportul social sczut

Analize sistematice recente au confirmat c persoanele care sunt izolate sau fr legturi cu alte persoane
prezint un risc crescut de deces prematur prin BCV. n
mod similar lipsa suportului social conduce la scderea
supravieuirii i la prognostic nefavorabil printre subiecii cu manifestri clinice de BCV (RR ~1,5-3,0)92,93.
Ostilitatea i furia
Ostilitatea este o caracteristic a personalitii caracterizat prin resimirea excesiv de nencredere, mnie
i furie i tendina de a se implica n relaii sociale agresive, maladaptative. O meta-analiz recent a confirmat
c furia i ostilitatea sunt asociate cu riscul crescut de
evenimente cardiovasculare att la subiecii sntoi,
ct i la persoanele cu BCV (HR 1,2)113. Incapacitatea
de a-i exprima furia ar putea fi de o importan deosebit, astfel c pacienii cu BCV care i suprim furia
prezint un risc crescut de evenimente cardiace adverse
(OR 2,9)114.
Stresul la locul de munc i n familie

n conformitate cu analizele studiilor recente, exist
dovezi medii c stresul profesional (de exemplu cerine
psihologice nalte, lipsa suportului social i presiunea la
locul de munc) reprezint factori de risc pentru evenimente cardiovasculare la sexul masculin [odds ratio
(OR) 1,5]94,95. Studiile care implic persoane de sex feminin sunt prea puine pentru a contura concluzii ferme94. Conflictele, situaiile de criz i condiiile stresante n viaa familial s-au demonstrat, de asemenea, a
crete riscul pentru BCV [hazard ratio (HR) ~2,7-4,0],
n special la femei (RR~2,9-4,0)96,97.
Depresia
Cteva analize sistematice i meta-analize au artat
c depresia clinic i simptomele depresive prezic evenimentele cardiovasculare (RR 1,6 i 1,9)98-100 i nrutesc prognosticul acestora (OR 1,6 i 2,4)100-102. Percepia suportului social pare s contracareze efectele
adverse ale depresiei103, n timp ce lipsa suportului social s-a dovedit a ntri efectele adverse ale depresiei104.
Anxietatea
Studii epidemiologice de amploare indic faptul c
atacurile de panic cresc riscul apariiei evenimentelor
cardiovasculare (HR 1.7 i, respectiv, 4.2)105,106, i anxietatea fobic, generalizat i atacurile de panic pot
nruti evoluia unei BCV deja instalate (OR 1,01 i,
respectiv, 2,0)107-109. n contradicie cu aceste constatri,
o analiz recent post-hoc a unui studiu prospectiv, de
cohort, de amploare a artat o mortalitate general, de
toate cauzele, sczut la pacienii anxioi cu BCV (HR
Tipul D de personalitate
n contrast cu simptomele anxioase i depresive izolate, care adesea apar episodic, tipul D de personalitate
(distressed) implic o tendin de durat de a exprima
un spectru larg de emoii negative (afectivitate negativ) i a-i inhiba autoexprimarea n raport cu alte persoane (inhibiie social). Tipul D de personalitate s-a
dovedit a prezice prognosticul nefavorabil la pacienii
cu BCV (OR 3,7), chiar i dup corecia pentru simptome depresive, stres i furie115.
3.4.2 Agregarea factorilor de risc psihosociali i
mecanisme bio-comportamentale
n majoritatea situaiilor, factorii de risc psihosociali
se cumuleaz la aceiai indivizi i grupuri. De exemplu,
att femeile, ct i brbaii cu status socio-economic
sczut i/sau stres cronic sunt mai predispui la a fi deprimai, ostili i izolai social116,117.
Mecanismele care leag factorii psihosociali de creterea riscului pentru BCV includ stilul de via nesntos (mai frecvent fumatul, alegeri alimentare nesntoase i mai puin efort fizic), creterea accesrilor
serviciilor de ngrijiri pentru sntate i scderea aderenei la recomandrile de schimbare a stilului de via
sau la medicaia cardiac88,90,116-119. Barierele financiare
pentru accesarea serviciilor de ngrijiri pentru sntate
au fost, de asemenea, demonstrate a avea efecte negative dup un infarct miocardic91.


Vol. 24, No. 4, 2014
n plus, persoanele i pacienii cu depresie i/sau

stres cronic prezint alterri ale funciei autonome (incluznd reducerea variabilitii ritmului cardiac), ale
axului hipotalamo-hipofizar i ale altor markeri endocrini, care afecteaz procesele hemostatice i inflamatorii, funcia endotelial i perfuzia miocardic117,118,120.
Riscul crescut la pacienii cu depresie poate fi parial
datorat, de asemenea, efectelor antidepresivelor triciclice121,122.

Meta-analize recente au artat c simptomele de
anxietate i tipul D de personalitate cresc riscul
pentru BCV i contribuie la rezultate clinice nefavorabile.
Lacune rmase
Exist dovezi limitate conform crora screeningul de rutin pentru factorii de risc psihosociali
contribuie la apariia a mai puine evenimente
cardiace viitoare, precum i faptul c screeningul
nu s-a tradus nc n alctuirea de modele utile
mbuntirii ngrijirilor strii de sntate.
3.4.3 Evaluarea factorilor de risc psihosociali

Evaluarea factorilor de risc psihosociali la pacienii
i persoanele cu factori de risc psihosociali este crucial ca mijloc de a stratifica eforturile preventive viitoare
n funcie de profilul de risc individual al pacientului.
Chestionarele standardizate pentru depresie, anxietate,
ostilitate, status socio-economic, suport social, stres
psihosocial i tipul D de personalitate sunt disponibile
n multe limbi i n multe ri115,123. Alternativ, o evaluare preliminar a factorilor psihosociali poate fi realizat
prin intermediul interviului clinic de ctre medic, conform Tabelului 6.
Tabelul 6. ntrebri cheie pentru evaluarea factorilor de risc psihosociali n practica clinic
Status socio-economic
Care este nivelul dumneavoastr educaional?
sczut
Suntei muncitor?
Stres la locul de munc i Pierdei controlul asupra ndeplinirii sarcinilor de serviciu?
familial
Considerai c munca dumneavoastr este rspltit inadecvat?
Avei probleme grave n relaia cu partenerul dumneavoastr
de via?
Izolarea social
Locuii singur?
V lipsete un confident apropiat?
Depresia
V simii drmat, deprimat i fr speran?
V-ai pierdut interesul i plcerea de a tri?
Anxietatea
V simii frecvent nervos, anxios sau marginalizat?
Vi se ntmpl frecvent s nu putei s oprii sau s controlai
ngrijorarea?
Ostilitatea
V simii frecvent furios pe lucruri mrunte?
V simii de multe ori deranjat de obiceiurile altor oameni?
Tipul D de personalitate
n general, v simii anxios, iritabil sau deprimat?
Evitai s v mprtii gndurile i sentimentele altor
persoane?
Prezena doar a nvmntului obligatoriu i/sau un

rspuns de da la una sau mai multe ntrebri indic un
risc mai mare dect cel apreciat cu diagramele SCORE sau cu categoriile prioritare. Relevana factorilor
psihosociali cu privire la calitatea vieii i implicaiile
medicale ar trebui discutat cu pacientul i, n plus,
trebuie luat n considerare managementul clinic adaptat pacientului (Seciunea 4.5). Screeningul de rutin
pentru depresie nu contribuie la un prognostic cardiac
mai bun, n absena schimbrilor n modul actual de
ngrijire cardiovascular124.
3.5 Ali biomarkeri pentru risc

Mesaje cheie
Noii biomarkeri prezint doar valoare suplimentar limitat atunci cnd se adaug evalurii riscului cardiovascular prin utilizarea algoritmului
SCORE.
Proteina C reactiv (CRP) de nalt sensibilitate
i homocisteina ar putea fi utilizate la persoane
cu risc cardiovascular moderat.
Recomandri privind biomarkerii inflamatori
Recomandri
Clasaa
CRP de nalt sensibilitate poate fi msurat ca parte a
evalurii de finee a riscului la pacienii cu un profil al
IIb
riscului cardiovascular neobinuit sau moderat.
CRP de nalt sensibilitate nu ar trebui msurat la
subiecii asimptomatici cu profil de risc sczut sau la
III
pacienii cu risc nalt, pentru a estima riscul de BCV
la 10 ani.
Fibrinogenul poate fi msurat ca parte a evalurii
de finee a riscului la pacienii cu un profil al riscului
IIb
cardiovascular neobinuit sau moderat.
Fibrinogenul nu ar trebui msurat la subiecii asimptomatici cu profil de risc sczut sau la pacienii cu risc
III
nalt, pentru a estima riscul de BCV la 10 ani.
Nivelb GRADE
Refc
Slab
125
Puternic
126
Slab
127
Puternic
127
Nivelb GRADE
Refc
Clasa de recomandri
Nivelul de eviden
c
Referine
a
b
Recomandri pentru biomarkerii trombotici

Recomandri
Clasaa
Homocisteina poate fi msurat ca parte a evalurii
de finee a riscului la pacienii cu un profil al riscului
IIb
cardiovascular neobinuit sau moderat.
Homocisteina nu ar trebui msurat pentru a monitoriIII
za prevenia riscului cardiovascular.
LpPLA2 poate fi msurat ca parte a evalurii de
finee a riscului la pacienii cu risc nalt de recuren a
IIb
evenimentelor aterotrombotice acute.
LpPLA2 = fosfolipaza asociat lipoproteinei
a
Clasa de recomandri
b
Nivelul de eviden
c
Referine
Slab
128
Puternic
128
Slab
129


Vol. 24, No. 4, 2014
Dei numrul de poteniali noi factori de risc se extinde tot mai mult, n fieccare an, acest numr se reduce
la un nivel apropiat de unitate o dat ce un posibil candidat a trecut de clasificarea dovezilor clinice. Biomarkeri emergeni au fost selectai din datele publicate, n
condiiile n care au fost testai ca alternative sau avnd
valoare superioar factorilor de risc clasici, pentru abilitatea de a prezice sau modifica morbiditatea sau mortalitatea cardiovascular la 10 ani. Doar biomarkerii
circulani evaluai prin metode standardizate sau validate (i identificai ca factori de risc a cror valoare
poate fi utilizat n practica clinic) au fost considerai
n aceste ghiduri, n contextul cost-eficienei pentru
evaluarea riscului individual n populaia general.
Dup ndeprtarea noilor biomarkeri cu relevan
pentru metabolismul glucidic, lipidic sau biomarkeri
specifici unui anumit organ, care sunt inclui ntr-o
seciune specific (a se vedea Seciunea 4), au fost identificate dou grupuri de biomarkeri sistemici relevani
pentru evaluarea riscului pentru BCV:
Inflamatori: hsCRP, fibrinogenul.
Protrombotici, cu risc trombogen: homocisteina, fosfolipaza asociat lipoproteinei (LpPLA2).
3.5.1 Factori de risc inflamatori: proteina C
reactiv nalt sensibil, fibrinogenul
Proteina C reactiv nalt sensibil a demonstrat consisten n studii prospective ample ca factor de risc
integrnd multipli factori de risc metabolici i inflamatori de grad sczut cu rol n dezvoltarea plcii de aterom instabile, cu o magnitudine a efectelor echivalent
cu a factorilor de risc clasici majori. Acest marker a dovedit un nivel moderat al riscului n evaluarea clinic a
factorilor de risc cardiovasculari majori125,126. Cu toate
acestea, exist cteva puncte slabe privind includerea
acestui nou biomarker pentru evaluarea riscului:
Multitudinea de factori de confuzie: dependen
de ali factori de risc majori clasici
Lipsa de precizie: fereastr diagnostic ngust
pentru valorile hsCRP i riscul de BCV.
Lipsa de specificitate: valoare similar privind
riscul pentru alte cauze de mortalitate i morbiditate non-cardiovascular (de exemplu alte boli
inflamatorii cu grad redus de inflamaie).
Lipsa relaiei doz-efect sau a relaiei de cauzalitate ntre modificrile nivelului hsCRP i riscul
de BCV.
Lipsa strategiilor terapeutice specifice sau a
agenilor terapeutici care s inteasc proteina C
reactiv circulant i care s determine scderea
incidenei BCV.
Pre mare al testrii comparativ cu dozarea factorilor de risc biologici clasici (de exemplu glicemia sau lipidele serice).
Situaii similare sunt i pentru fibrinogen127.
3.5.2 Factori de risc trombotici

Homocisteina
S-a demonstrat c homocisteina este un factor de
risc independent pentru BCV. Intensitatea efectului
asupra riscului este modest, i consecvena adesea lipsete, n principal din motive nutriionale, metabolice
(de exemplu, bolile renale), i ale stilului de via128. n
plus, studiile intervenionale care au folosit vitamina B
pentru a reduce nivelul plasmatic al homocisteinei s-au
dovedit ineficiente n reducerea riscului de BCV128.
Homocisteina rmne un marker de linia a doua
pentru estimarea riscului BCV i datorit costului de
determinare.
Fosfolipaza A2 asociat lipoproteinei
Recent s-a stabilit c LpPLA2 reprezint un marker
important ca factor de risc independent pentru instabilitatea plcii i evenimente aterotrombotice. Intensitatea efectului asupra riscului rmne modest la nivelul populaiei generale. LpPLA2 rmne marker de a
doua linie pentru estimarea riscului BCV i datorit
costurilor de determinare129.
n general, utilizarea acestor biomarkeri poate aduce un beneficiu suplimentar n anumite situaii, pentru
a evalua mult mai precis riscul de BCV n subgrupuri
specifice de pacieni, cu risc moderat, neobinuit sau
nedefinit (de exemplu, pacieni asimptomatici fr
multiplii factori de risc majori clasici, dar care sunt
cunoscui cu o afectare rar metabolic, inflamatorie,
endocrin, sau cu statut social asociat cu ateroscleroza
sau semne de progresie aterosclerotic).
Lacune rmase
Pentru utilizarea, att a biomarkerilor bine cunoscui,
ct i pentru biomarkerii viitori, exist nevoia de a redefini subgrupuri specifice (cu risc intermediar, nedefinit,
sau neobinuit de BCV) care ar beneficia cel mai mult
de utilizarea acestor biomarkeri, n special n prevenia
primar.
3.6 Metode imagistice n prevenia bolilor
cardiovasculare
Mesaje cheie
Metodele imagistice pot fi relevante n evaluarea
riscului de BCV la persoanele cu risc moderat.

Consecinele aterosclerozei coronariene pot fi evaluate obiectiv neinvaziv, folosind o varietate de tehnici,
cum ar fi testarea ECG la efort pe biciclet sau covor
rulant, ecocardiografia de stres, sau scintigrafia miocardic. Din pcate, moartea subit de cauz cardiac este
pentru multe persoane prima manifestare a BCV. Identificarea pacienilor asimptomatici, dar bolnavi, este
crucial pentru un program de prevenie adecvat
La fiecare nivel de expunere la factori de risc, exist
o variaie substanial n ceea ce privete nivelul afectrii aterosclerotice. Aceast variaie a bolii este probabil datorat susceptibilitii genetice, combinaiei ntre
factori de risc diferii, precum i interaciunii dintre
genetic i factorii de mediu. Astfel diagnosticarea bolii
subclinice poate fi util n mbunatirea prediciei riscului de BCV. Testele non-invazive, cum ar fi ecografia
carotidian, tomografia computerizat cu fascicul de
electroni, tomografia computerizat multislice, indicele glezn bra i tehnicile de rezonan magnetic,
ofer o modalitate de msurare i monitorizare direct
sau indirect a aterosclerozei la persoanele asimptomatice, dar trebuie s se ia in considerare raportul costeficien.
3.6.1 Depistarea precoce prin rezonan
magnetic a bolilor cardiovasculare la pacienii
asimptomatici
Rezonana magnetic a fost analizat ca mijloc de
evaluare a stenozei arterelor coronare. Valoarea acestei
tehnici este nc discutabil141,142. n prezent, sensibilitatea i specificitatea acestei tehnici nu sunt suficient de
mari pentru a putea fi folosit n efectuarea screeningului pentru stenozele coronariene la persoanele asimptomatice.
Recent, detectarea prin RMN a remodelrii pozitive a peretelui coronarian la pacienii asimptomatici cu
ateroscleroz subclinic, a deschis un nou domeniu de
cercetare n prevenia BCV143. In vitro, RMN-ul poate

Vol. 24, No. 4, 2014
diferenia componentele plcii de la nivel carotidian,

aortic i coronarian, obinute la autopsie144. mbuntirea rapid a acestei tehnici a condus la utilizarea imagisticii 3D, care permite in vivo distincia dintre pereii
vasculari normali i cei modificai145. n prezent, RMNul reprezint o tehnic de cercetare promitoare, dar
utilizarea sa de rutin rmne limitat, nefiind nc
adecvat pentru identificarea pacienilor cu risc crescut de BCV146.
3.6.2 Scorul de calciu coronarian
Calcifierile coronariene indic ateroscleroz coronarian147. Pe de alt parte, arterele coronare aterosclerotice nu prezint obligatoriu calcificri. Extinderea calcificrilor se coreleaz cu gradul de afectare aterosclerotic coronarian147. Calcifierea coronarian nu este
un indicator nici de stabilitate i nici de instabilitate a
plcii aterosclerotice148. La pacienii cu SCA, gradul de
calcifiere coronarian este mult mai pronunat dect
n grupurile de control fr boal coronarian149. Mai
mult dect att, la pacienii cu SCA150, s-a observat prezena componentelor inflamaiei, subliniindu-se astfel
conceptul de evaluare a afectrii totale aterosclerotice
coronariene prin cuantificarea scorului de calciu coronarian151.
Majoritatea datelor privind evaluarea prezenei i
amploarea calcificrilor coronariene sunt legate de utilizarea scorului Agatston152.
Recent s-a sugerat c acest scor ar trebui nlocuit cu
variabile volumetrice, cum ar fi: volumul total de calciu (mm3), masa de calciu (mg), sau densitatea de calciu (mg/mm3). Din punct de vedere clinic, nu se tie
nc dac aceste noi variabile sunt superioare scorului
Agatston153. Valoarea scorului poate fi mbunatit
i mai mult dac s-ar lua n considerare distributia n
funcie de vrst i sex153.
Prezena calcificrilor coronariene nu corespunde
neaprat cu existena unor stenoze coronariene sem-
Recomandri privind metodele imagistice

Recomandri
Msurarea indicelui intim-medie carotidian i/sau screeningul pentru plci de aterom prin ecografie carotidian ar trebui luate n considerare
pentru cuantificarea riscului cardiovascular la adulii asimptomatici cu risc moderat.
Msurarea indicelui glezn-bra ar trebui luat n considerare pentru cuantificarea riscului cardiovascular la adulii asimptomatici cu risc
moderat.
Tomografia computerizat pentru calcularea scorului de calciu coronarian ar trebui luat n considerare pentru cuantificarea riscului cardiovascular la adulii asimptomatici cu risc moderat.
Electrocardiografia de efort poate fi luat n considerare pentru cuantificarea riscului cardiovascular la aduli asimptomatici cu risc moderat (incluznd adulii sedentari, n vederea iniierii unui program de exerciii fizice intense) n special cnd atenia este ndreptat asupra unor markeri
non-electrocardiografici cum ar fi capacitatea de efort.
Nivel de eviden
c
Bibliografie
a
b
Clasaa
Nivelb
GRADE
Refc
IIa
Puternic
130-132
IIa
Puternic
133-135
IIa
Slab
136-138
IIb
Puternic
46, 139, 140

Vol. 24, No. 4, 2014
nificative, deoarece specificitatea sa n ceea ce privete

prezena unei stenoze 50% este de numai 50%. Erorile n ceea ce privete scorul de calciu coronarian i
extrapolarea acestuia ca semnificnd boal arterial
coronarian, sunt datorate utilizrii greite a definiiei:
n timp ce prezena calcificrilor coronariene indic o
afectare coronarian (ateroscleroza coronarian), acesta nu reflect neaprat boala coronarian ischemic definit ca ngustarea coronarin 50%.
Pe de alt parte, scorul de calciu coronarian are o
valoare predictiv negativ foarte nalt: scorul Agatston de 0 are o valoare predictiv negativ de aproape
100% pentru excluderea unei ngustri coronariene
semnificative154. Cu toate acestea, studiile recente au
pus la ndoial valoarea predictiv negativ a scorului
de calciu, fiind posibil prezena unei stenoze semnificative n lipsa calcificrilor coronariene. Aceasta este
mai frecvent ntalnit n angina pectoral instabil sau
infarctul miocardic fr supradenivelare de segment ST
(NSTEMI), dect in angina pectoral stabil, i apare
mai frecvent la pacienii tineri155. Multe studii prospective au demonstrat relevana prognostic a cantitii de
calciu coronar156.
Scorul Agatston este un marker independent de risc
n ceea ce privete boala coronarian157 i impactul prognostic158. Studiul Rotterdam asupra calcificrilor coronariene a artat o cretere de 12 ori a riscului de infarct
miocardic-independent de factorii clasici de risc-chiar
i la persoanele n vrst159.
Dei scorul de calciu este larg utilizat n prezent, este
cel mai bine aplicabil la pacienii cu risc moderat137.
Expunerea la radiaii cu tehnicile alese n mod corespunztor este de aproximativ 1 mSv. Studii recente au
artat, de asemenea, c angio-CT coronarian multislice
cu nivel de radiaie sczut, este foarte eficient n re-stratificarea post-test a pacienilor, n grupuri de risc sczut
sau nalt160.
3.6.3 Ecografia carotidian
Studiile populaionale au demonstrat o corelaie ntre severitatea aterosclerozei ntr-un teritoriu arterial i
implicarea altor artere130. Prin urmare, depistarea precoce a bolii arteriale la persoanele aparent sntoase
s-a concentrat asupra teritoriului arterial periferic i al
arterelor carotide. Evaluarea riscului folosind ecografia carotidian se face prin msurarea IMT (indicelui
intima-medie) i prin detectarea plcilor i caracteristicilor lor.
IMT nu este doar o metod de cuantificare a aterosclerozei precoce, fiind aplicabil i pentru evaluarea
hipertrofiei/hiperplaziei musculaturii netede, care poa-

te fi corelat cu factori genetici, hipertensiunea arterial i scleroza la vrstnici132. Dei exist o cretere
gradual a riscului cardiovascular cu creterea IMT, o
valoare mai mare de 0,9 mm este considerat anormal. Persoanele fr boal cardiovascular cunoscut cu
un IMT crescut, au un risc mare de evenimente cardiace i accident vascular cerebral. Dei riscul relativ de
evenimente este uor mai sczut dup corecia statistic pentru prezena factorilor de risc tradiionali, riscul
rmne ridicat la un IMT mai mare130.
Cnd IMT este folosit pentru a prezice incidena
unui accident vascular cerebral, riscul este gradual, dar
non-linear, cu un risc n cretere mai rapid la un IMT
mai mic dect la un IMT mai mare130. Riscul de evenimente cardiace la 4-7 ani la pacienii fr boal cardiovascular la momentul iniial este, de asemenea, legat
non-linear de IMT131.
Placa aterosclerotic este definit ca o structur focal de pe interiorul peretelui vascular cu o grosime de
cel puin 0,5 mm (sau peste 50% din IMT-ul de la acest
nivel), sau orice grosime a IMT 1,5 mm. Plcile pot fi
caracterizate prin numr, dimensiune, neregulariti, i
echodensitate ( hipoecogene vs calcificate). Plcile sunt
corelate, att cu boala coronarian obstructiv, ct i cu
riscul de evenimente cerebrovasculare. Plcile hipoecogene implic un risc crescut de evenimente cerebrovasculare, comparativ cu cele calcificate.
Caracteristicile plcii evaluate prin ecografia carotidian s-au dovedit a fi parametrii de predictivitate a
evenimentelor cerebrale ischemice ulterioare131. Pacienii cu plci stenotice hipoecogene au avut un risc mai
mare de evenimente cerebrovasculare, comparativ cu
subiecii cu alte tipuri de plci. Ecografia carotidian
repezint o tehnic non-invaziv de evaluare a aterosclerozei subclinice. IMT-ul carotidian este un factor
predictiv independent pentru evenimente cerebrale i
coronariene, mai ales n cazul sexului feminin. Prin
urmare, ecografia carotidian, pe lng factorii de risc
uzuali, poate aduce informaii suplimentare, care pot
ajuta n luarea deciziei asupra necesitii instituirii tratamentului medical pentru prevenia primar.
A fost demonstrat ca rigiditatea arterial aduce date
suplimentare pentru stratificarea pacieilor. Creterea
rigiditii arteriale este de obicei legat de leziunile
peretelui arterial, aa cum apare la pacienii hipertensivi161,162.
3.6.4 Indicele glezn-bra
Indicele glezn-bra (IGB) este un test reproductibil
i uor de realizat pentru detectarea bolii aterosclerotice asimptomatice. Un IGB <0,9 indic stenoz de cel

puin 50% ntre aort i arterele distale ale membrului

inferior. Datorit unei sensibiliti (79%) i specificiti
acceptabile, un IGB <0,90 este considerat marker fidel
al bolii arteriale periferice133. O valoare a IGB, indicnd afectare arterial periferic semnificativ, aduce
un plus de valoare anamnezei, pentru c 50-89% dintre
pacienii cu un IGB <0,9 nu au claudicaie tipic134. Un
IGB <0,9 poate fi identificat la 12-27% dintre pacienii
asimptomatici cu vrsta peste 55 ani. Chiar i n cadrul populaiei vrstnice (71-93 de ani), un IGB sczut
identific suplimentar un subgrup cu risc mai crescut
de boal coronarian. IGB poate prezice, de asemenea,
dezvoltarea ulterioar a anginei, a infarctului miocardic, a insuficienei cardiace congestive, a CAGB, a accidentului vascular cerebral sau necesitatea chirurgiei
carotidiene135. Valoarea IGB este invers proporional
cu riscul cardiovascular163.
3.6.5 Oftalmoscopia
S-a demonstrat c extinderea aterosclerozei arterelor retiniene se coreleaz cu extinderea aterosclerozei
coronariene i cu nivelele serice ale colesterolului, trigliceridelor i apoproteinei B164. Totui, locul ei n evaluarea riscului bolilor vasculare, rmne neprecizat.
Screeningul ecografic vascular este rezonabil
pentru evaluarea riscului la indivizii asimptomatici cu risc moderat;
Evaluarea calcificrilor arterelor coronare ar
putea fi rezonabil pentru evaluarea riscului cardiovascular la adulii asimptomatici cu risc moderat.
Lacune rmase
Rolul computer tomografiei pentru screeningul
pacienilor asimptomatici necesit investigaii
suplimentare;
Nu exist nc studii prospective care s demonstreze valoarea CT-ului coronarian (nivel A de
eviden);
Imagistica prin rezonan magnetic pentru detectarea plcilor vasculare ar putea fi de interes
n evaluarea riscului cardiovascular la pacienii
asimptomatici, dar studiile nu sunt nc convingtoare.
3.7 Alte boli cu risc crescut pentru afeciunile
cardiovasculare
Ateroscleroza este o boal inflamatorie n care mecanismelel imune interacioneaz cu factorii de risc

Vol. 24, No. 4, 2014
metabolici pentru a iniia, propaga i activa leziunile la

nivelul arborelui arterial170. Mai multe afeciuni n care
procesele inflamatorii infecioase sau neinfecioase
domin tabloul clinic, sunt asociate cu o rat crescut de evenimente cardiovasculare. Conceptul optim de
prevenie n cadrul acestor patologii nu este stabilit i
nu exist studii randomizate pentru a evalua prognosticul. Managementul tuturor factorilor de risc pare totui
indicat, chiar i n absena studiilor randomizate.
3.7.1 Gripa
Epidemiile de grip sunt asociate cu o rat crescut
de evenimente cardiovasculare. Vaccinarea antigripal, ca o msur de prevenie n populaia general,
s-a asociat cu o reducere foarte bun cost-eficien a
evenimentelor clinice171. Vaccinare antigripal anual
este recomandat pacienilor cu boal cardiovascular
diagnosticat172.
3.7.2 Boala renal cronic
Hipertensiunea, dislipidemia i diabetul zaharat,
sunt frecvent ntlnite la pacienii cu boal renal cronic. Acetia sunt factori de risc majori pentru dezvoltarea i progresia disfunciei endoteliale i a aterosclerozei i contribuie la progresia insuficienei renale totui, aceti pacieni tind s fie tratai mai puin
agresiv, dect cei cu funcie renal normal165. n boala
renal cronic, mediatorii inflamaiei i promotorii calcificrii, au nivele crescute, iar inhibitorii calcificrii au
nivele reduse, ceea ce favorizeaz calcificrile vasculare
i afectarea vascular136. Microalbuminuria crete riscul cardiovascular de dou pn la patru ori. O RFG
sczut este un indicator pentru boal cardio-vascular
i mortalitate de orice cauz. ntr-un studiu mare de cohort, anemia, scderea RFG i microalbuminuria, au
fost asociate independent cu boala cardiovascular i,
atunci cnd toate erau prezente, boala cardiovascular
a fost frecvet, iar supravieuirea a fost redus173.
Recomandrile privind alte boli cu risc crescut pentru afeciunile
cardiovasculare
Recomandri
Clasaa Nivelb GRADE
La pacienii cu boal renal cronic, factorii de risc treI
C
Puternic
buie controlai la fel ca la indivizii cu risc foarte nalt
Toate persoanele cu apnee obstructiv de somn ar
trebui evaluate medical, inclusiv prin stratificarea i
IIa
A
Puternic
managementul riscului
Toi brbaii cu disfuncie erectil ar trebui s fie evaluai medical, inclusiv prin stratificarea i managementul
IIa
B
Puternic
riscului.
Clas de recomandare
Nivel de eviden
c
Bibliografie
a
b
Refc
165,
166
167,
168
169

Vol. 24, No. 4, 2014
Exist o asociere cantitativ ntre scderea RFG i

riscul cardiovascular: pacienii cu funcie renal moderat sczut (stadiul 3, RFG 30-59 ml/min/1,73 m2), au
un risc mai crescut de 2 pn la 4 ori, n comparaie cu
persoanele fr boal renal cronic. Riscul crete de
4 pn la 10 ori n stadiul 4 (RFG 15-29 ml/min/ 1,73
m2) i de 10 pn la 50 de ori n stadiul 5 de insuficien renal (stadiul final) (RFG <15 ml/min/1,73 m2 sau
stadiul de dializ)136. Controlul dislipidemiei pare util
la un numr mare de pacieni cu boal renal cronic
avansat, fr istoric de infarct miocardic sau revascularizare coronarian: o reducere a fraciunii lipoproteinelor cu densitate mic (LDL) de 0,85 mmol/l (33
mg/dl) cu 20 mg simvastatina i 10mg ezetimib zilnic,
a redus incidena evenimentelor majore: infarct miocardic non-fatal, moarte de cauz coronarian, AVC
non-hemoragic sau orice procedur de revascularizare
arterial174.
3.7.3 Sindromul de apnee n somn
Sindromul de apnee n somn (SAS) este caracterizat
prin obstrucia recurent, parial sau complet, a cilor aeriene superioare, n timpul somnului. Estimativ,
afecteaz 9% dintre adulii de sex feminin i 24% dintre
adulii de sex masculin175.
Stimulrile repetate ale activitii simpatice, creterea presiunii sanguine i stresul oxidativ, produse de
durere i episoadele de hipoxie asociate cu un nivel
crescut al mediatorilor inflamaiei, sunt considerai a
fi promotori ai disfunciei endoteliale i ai aterosclerozei176. SAS a fost asociat cu o cretere cu 70% a riscului
relativ de mortalitate i morbiditate cardiovascular177.
Riscul se coreleaz la brbaii ntre 40 i 70 de ani cu
indexul apnee-hipopnee167. Screeningul i tratamentul
SAS la pacienii cu boal arterial coronarian178 i hipertensiune arterial poate duce la scderea evenimentelor cardiace i a morii cardiace168.
3.7.4 Disfuncia erectil
Disfuncia erectil (DE), definit ca i inabilitatea
constant a unui brbat de a atinge i menine erecia
satisfacatoare pentru actul sexual, afecteaz ntr-o anumit msur 52% dintre adulii de sex masculin cu
vrste cuprinse ntre 40 i 70 de ani. Se poate datora
unor factori psihologici, neurologici, hormonali, arteriali sau a insuficienei cavernoase, sau unei combinaii
a acestora179-181. DE are o prevalen mare la indivizii cu
multipli factori de risc cardiovasculari i la cei cu boli
cardiovasculare. DE este un marker pentru boala cardiovascular i un predictor al evenimentelor viitoare
n rndul brbailor de vrst mijlocie i avansat, dar
nu mai mare dect cel oferit de scorul de risc Framingham182-184. Modificarea stilului de via i farmacote-

rapia factorilor de risc sunt eficiente n mbuntirea

funciei sexuale a brbailor cu DE169.
3.7.5 Bolile autoimune
3.7.5.1 Psoriazisul
Psoriazisul se pare c este un factor de risc independent pentru infarctul miocardic. Fiziopatologia psoriazisului este caracterizat de creterea activitii antigenilor, a activrii celulelor T i a citokinelor T helper
tip 1, rezultnd plci roii groase, solzoase, iar la unii
pacieni, artrit. Psoriazisul este, de asemenea, asociat
cu markeri inflamatori sistemici, precum niveluri serice crescute de PCR. Riscul de infarct miocardic asociat psoriazisului, este cel mai mare la pacienii tineri cu
forme severe, se atenueaz cu vrsta i rmne crescut
chiar i dup controlul factorilor de risc cardiovasculari clasici. Pacienii cu psoriazis clasificat ca i sever,
au avut un risc mai mare de infarct miocardic dect
pacienii cu forme uoare, fapt concordant cu ipoteza conform creia activitatea imunologic crescut n
psoriazis este relaionat cu un risc crescut de infarct
miocardic i moarte cardiovascular185,186.
3.7.5.2 Artrita reumatoid
Pacienii cu artrit reumatoid au risc dublu fa de
populaia general, de a suferi un infarct miocardic. De
asemenea, acetia au o rat mai crescut de mortalitate dup infarctul miocardic, fapt care ar putea explica
parial sperana de via redus a acestora (5-10 ani mai
puin dect pacienii fr aceast afeciune). Riscul cardiovascular este crescut din stadiile incipiente ale bolii,
iar acest risc crescut, dincolo de factorii de risc clasici,
este posibil legat de inflamaia sitemic i de statusul
protrombotic.
Modificarea factorilor de risc clasici prin modificarea stilului de via, inclusiv modificrile dietetice,
oprirea fumatului, exerciiul fizic zilnic i tratamentul
medicamentos corespunztor, pot avea importan deosebit n reducerea riscului la pacienii cu artrit reumatoid sau psoriazis.
Studiile observaionale nerandomizate, constat reducerea ratei evenimentelor vasculare i a morii cardiovasculare la pacienii cu artrit reumatoid i psoriazis, care au fost tratai sptmnal cu Metotrexat cu
doze ntre 10 i 20 mg187,188.
3.7.5.3 Lupusul eritematos
Lupusul eritematos sistemic este asociat cu disfuncie
endotelial i cu un risc crescut de boal coronarian,
care nu este explicat de factorii de risc clasici pentru
cardiopatia ischemic.

Inflamaia sistemic cronic, la pacienii cu lupus

eritematos sistemic, are drept rezultat disfuncia microvascular, cu anomalii n ceea ce privete fluxul absolut al vascularizaiei miocardice i al rezervei coronariane de snge. Disfuncia microvascular coronarian
este un marker precoce al aterosclerozei coronariene
accelerate i poate contribui la creterea mortalitii i
morbiditii cardiovasculare la aceti pacieni189.
3.7.6 Parodontoza
Parodontoza este asociat cu disfuncie endotelial,
ateroscleroz i cu un risc crescut de infarct miocardic
i AVC. Factori intricai, totui, precum nivelul socioeconomic sczut i fumatul, joac probabil un rol important. Paradontoza poate fi cosiderat un indicator
de risc pentru statusul alterat de sntate cardiovascular, i astfel, este necesar tratamentul ei, precum i managementul celorlali factori de risc cardiovasculari190.
3.7.7 Boala vascular dup radioterapie
Incidena cardiopatiei ischemice i a AVC-ului se
menine crescut muli ani dup radioterapie pentru
limfoame sau cancere mamare, sau pentru cancere la
nivelul capului sau gtului191,192.
Din studii descriptive, leziunile prezint modificri
tipice de ateroscleroz, inclusiv acumulare de lipide, inflamaie i tromboz193. Dup radioterapie, pacienii ar
trebui s-i optimizeze profilul factorilor de risc. Astfel,
ar putea fi indicata utilizarea de statine.
3.7.8 Boala vascular post transplant
Vasculopatia alogrefei cardiace este principala cauz de morbiditate i mortalitate tardiv la pacienii cu
transplant de cord. Dei este un proces complex multifactorial, datorat mecanismelor patogenice imune i
non-imune, management-ul vasculopatiei alogrefei
cardiace s-a axat pe modificrile factorilor de risc clasici i optimizarea imunosupresiei. Factorii de risc nonimuni importani includ dislipidemia, hipertensiunea
arterial, diabetul zaharat tip II i hiperhomocisteinemia. Administrarea statinelor mbuntete funcia
endotelial, ncetinete progresia vasculopatiei de alogref cardiac i mbunatete supravieuirea194.
Tratamentul paradontozei mbuntete disfuncia endotelial, unul dintre cele mai precoce
semne de ateroscleroz.
Lacune rmase
Lipsesc studiile randomizate, cu excepia pacienilor cu boal vascular dup transplant.

Vol. 24, No. 4, 2014
4.CUM POATE FI FOLOSIT PREVENIA BOLILOR

CARDIOVASCULARE?
4.1. Principii pentru schimbarea comportamentului
Mesajul cheie
Metodele cognitiv-comportamentale sunt eficiente n sprijinirea populaiei pentru adoptarea
unui stil de via sntos.
Recomandri pentru modificarea stilului de via
Recomandri
Clasaa Nivelb
Sunt recomandate strategiile congnitiv-comportamentale cu dovezi stabilite (ex:interviul motivaional)
I
A
pentru a facilita schimbarea stilului de via
Cadrele medicale specializate (ex:asistente medicale,
dieteticieni, psihologi, etc.) ar trebui implicate oricnd
II a
A
este necesar i posibil
La indivizii cu risc cardiovascular foarte nalt sunt
recomandate interveniile multidisciplinare, integrnd
I
A
educaia n sensul unui stil de via sntos i resurse
medicale, efortul fizic, managementul stresului i consilierea n privina factorilor de risc psihosociali.
GRADE
Refc
Puternic
195,
196
Puternic
185,
197,
198
Puternic
195,
197,
199,
200
Nivel de eviden
c
Bibliografie
a
b
4.1.1. Introducere: de ce este dificil modificarea

stilului de via?
Stilul de via este de obicei bazat pe modele comportamentale de lung durat. Aceste modele sunt
implementate din timpul copilriei i adolescenei rezultate din interaciunea dintre factorii de mediu i cei
genetici, i sunt meninute i chiar promovate de mediul social al individului ca i adult. Prin urmare, pot
fi observate diferene semnificative n ceea ce privete
comportamentul sntos dintre indivizi, dar i dintre
grupurile sociale. n plus, aceti factori mpiedic capacitatea de a adopta un stil de via sntos, ca i sfaturile confuze sau complexe ale personalului medical.
Creterea gradului de contientizare a acestor factori
faciliteaz empatia i consilierea (sfaturi simple i explicite), favoriznd astfel modificarile comportamentale.
4.1.2. Comunicarea eficient i strategiile
cognitiv-comportamentale ca i mijloace de
schimbare a stilului de via
O interaciune pozitiv i prietenoas este un instrument puternic n creterea capacitii unui individ de a face fa bolii i de a respecta recomandrile
privind modificrile stilului de via i utilizarea medicaiei. Sprijinul social oferit de cadrele medicale este
important pentru a ajuta indivizii s menin obiceiurile sntoase i pentru a urma sfaturile medicale. Este
foarte important analizarea experienelor individuale
ale fiecrui pacient, gndurile i grijile, cunotiinele

Vol. 24, No. 4, 2014
anterioare i circumstanele vieii de zi cu zi. Consilierea individual constituie baza n ctigarea motivaiei
pacientului i angajamentul acestuia. Deciziile luate
trebuie mprtite de ctre cadrul medical i pacient
(incluznd i partenerul de via i familia individului)
n cea mai mare msur posibil, asigurndu-se astfel
implicarea activ, att a individului, ct i a familiei n
modificarea stilului de via i n aderena la tratament.
Utilizarea urmatoarelor principii de comunicare, va facilita tratamentul i prevenia bolilor cardiovasculare
(Tabelul 7).
Tabelul 7. Principiile comunicrii eficiente pentru a facilita modificarea
stilului de via
Petrecerea unui timp suficient cu pacientul pentru a crea o relaie terapeutic - chiar i cteva
minute n plus pot face diferena.
Cunoaterea prerii personale a individului referitor la boal i la factorii de risc.
ncurajai exprimarea nelinitilor i anxietilor, grijilor i evaluai motivaia pentru schimbarea stilului de via i ansele de succes.
Vorbii cu individul pe nelelsul su i spijinii-l la fiecare mbuntire a stilului de via.
Punei ntrebri pentru a verifica dac individul a neles sfaturile date i are sprijinul de care
are nevoie pentru a le urma.
Acceptarea faptului c schimbarea obiceiurilor vechi poate fi dificil i c schimbrile graduale
susinute sunt mai frecvent permanente dect schimbrile rapide.
Acceptai c indivizii pot avea nevoie de sprijin pentru o perioad mai lung de timp i c pot
fi necesare eforturi repetate pentru a ncuraja i menine un stil de via sntos la muli
indivizi.
Asigurai-v c toate cadrele medicale implicate furnizeaz informaii consecvente.
Tabelul 8. Zece pai strategici pentru o mai bun consiliere n schimbarea stilului de via203
1. Dezvoltai o alian terapeutic.
2. Consiliai toate persoanele la risc, cu sau fr boal cardiovascular manifest.
3. Sprijinii persoanele s neleag relaia dintre stilul de via si sntate.
4. Ajutai persoanele s observe barierele n schimbarea stilului de via.
5. Ctigai implicarea persoanelor n schimbarea stilului de via.
6. Implicai persoanele n identificarea i selectarea factorilor de risc care trebuie schimbai.
7. Utilizai o combinaie de strategii, inclusiv consolidarea capacitatii proprii de schimbare.
8. Elaborai un plan de schimbare a stilului de via.
9. Implicai i alt personal medical ori de cate ori este posibil.
10. Urmrii progresele prin controale periodice.
n plus, personalul medical poate construi strategii

cognitiv-comportamentale pentru a aprecia ideile, atitudinea i convingerile persoanei privind capacitatea
de schimbare a comportamentului, ct i contextul n
care ncercrile de schimbare vor fi fcute. Interveniile
comportamentale cum ar fi interviul motivaional201
cresc motivarea i eficiena proprie196. Tentativele anterioare negative, euate, de schimbare a stilului de via,
duc frecvent la o eficacitate mai redus a schimbrilor ulterioare, conducnd frecvent la un nou eec. Un
pas important n transformarea experienelor negative
n pozitive, este acela de a ajuta individul sa i fixeze
obiective realiste, iar fixarea obiectivelor combinat cu
automonitorizarea comportamentului ales, sunt prin-

cipalele metode de obinere a unui rezultat pozitiv202.

Acestea vor crete eficiena proprie n meninerea comportamentului ales, ulterior putnd fi fixate noi obiective. Progresul n pai mici este unul din elementele eseniale ale schimbrii stilului de via pe termen lung202.
Modul n care oferim informaiile necesare trebuie s
fie n concordan cu ideile i sentimentele pacientului.
Cum aceasta este o aptitudine clinic particular, o pregtire n domeniul comunicrii este important pentru
personalul medical calificat.
Cei Zece pai strategici i-au dovedit eficiena n
mbuntirea consilierii n ceea ce privete schimbarea
stilului de via (Tabelul 8)203.
4.1.3 Interveniile comportamentale multimodale
Combinnd cunotinele si experiena clinicienilor
(cum ar fi medici, asistente, psihologi, nutriioniti, experi n recuperare medical i medicin sportiv) n
intervenii comportamentale multimodale, putem optimiza eforturile de prevenie35,202,204,205.
Interveniile comportamentale multimodale sunt recomandate, n special, pentru persoanele cu risc foarte
nalt i pentru cei cu boal cardiovascular clinic manifest. Aceste intervenii includ promovarea unui stil
de via sntos, constnd din modificri ale nutriiei,
antrenament fizic, tehnici de relaxare, controlul greutii, programe de renunare la fumat pentru fumtorii
tenace204. Acestea mbuntesc capacitatea de a face
fa bolii, aderena la tratament, eforturile de schimbare comportamental i prognosticul cardiac195,197,198.
Factorii de risc psihosociali (stresul, izolarea social
i emoiile negative), care pot aciona ca i piedici n
schimbarea comportamental ar trebui abordai n sesiuni adaptate, individuale sau n cadrul edinelor de
consiliere de grup195,204.
Exist dovezi c interveniile mai ample/de mai lung durat pot duce la rezultate mai bune pe termen
lung n ceea ce privete schimbrile comportamentului
i rezultatele somatice195,202. Persoanele cu statut socioeconomic sczut, de vrst naintat sau sex feminin ar
putea avea nevoie de programe adaptate cu scopul de a
rspunde nevoilor lor specifice n ceea ce privete informarea i suportul emoional202,206.
Informaii noi importante
Strategiile cognitiv-comportamentale s-au dovedit a fi componente eseniale ale interveniilor
care vizeaz schimbarea stilului de via.
Limite
n ceea ce privete stabilirea celor mai eficiente
intervenii n grupuri specifice (de exemplu, t


Vol. 24, No. 4, 2014
nr - vrstnic, sex masculin feminin, statut socio-economic sczut-ridicat) dovezile sunt limitate.
4.2 Fumatul
Mesaje-cheie
Schimbarea statutului de fumtor este o piatr de
temelie n mbuntirea strii de sntate cardiovascular.
Msurile de sntate public care includ interzicerea fumatului sunt cruciale pentru perceperea
public a fumatului ca un pericol important pentru sntate.
Recomandri n ceea ce privete fumatul
Recomandri
Clasa
Toate tipurile de fumat sunt un puternic i independent
I
factor de risc pentru BCV i trebuie s fie evitate.
Expunerea la fumatul pasiv crete riscul de BCV i
trebuie
I
s fie evitat.
Tinerii trebuie s fie ncurajai s nu se apuce de
I
fumat.
Tuturor fumtorilor ar trebui s li se acorde
sfaturi de renunare la fumat i s li se ofere
I
asisten.
Nivelb GRADE
Refc
207,
208
Puternic
Puternic
209,
210
Puternic
211
Puternic
212,
213
BCV=boal cardiovascular
a
Clas de recomandare
b
Nivel de eviden
c
Referine
4.2.1 Introducere
Fumatul este o cauz stabilit pentru o serie larg de
boli i este responsabil pentru 50% din totalul deceselor
evitabile la fumtori, jumtate dintre acestea fiind datorate BCV. Fumatul este asociat cu creterea riscului
pentru toate tipurile de BCV - cardiopatie ischemic,
accident vascular cerebral ischemic, boal arterial
periferic i anevrism al aortei abdominale. Conform
estimrilor din SCORE, riscul de evenimente cardiovasculare fatale la 10 ani este aproximativ dublu la
fumtori. Cu toate acestea, n timp ce riscul relativ de
infarct miocardic la fumtorii >60 de ani este dublu, la
fumtorii <50 ani este de 5 ori mai mare fa de nefumtori214,215.
Dei frecvena fumatului n Europa este n scdere,
fumatul este nc foarte rspndit n rndul persoanelor cu un nivel de educaie sczut; reflectarea diferenelor n educaie asupra ratei de abandonare a fumatului s-a observat n mai multe ri europene n ultimii
ani214,216,217. n studiul EUROASPIRE III, 30% dintre
participani au fumat pn la momentul evenimentului
coronarian, numrul acestora scznd la jumtate dup
o perioada medie de 1,5 ani. De asemenea, n urma
acestui studiu s-a constatat c folosirea tratamentului
de renunare la fumat bazat pe dovezi a fost insuficient

utilizat33.
n trecut, fumatul era practicat n special de ctre
brbai, dar n ultimii ani femeile i-au ajuns sau chiar
au depit nivelul fumatului nregistrat n rndul brbailor, n multe regiuni. Riscul asociat fumatului este
proporional mai crescut la femei fa de brbai215,218.
Acest fapt ar putea fi legat de diferenele n metabolizarea nicotinei, deoarece femeile metabolizeaz mai
repede nicotina dect brbaii, n special femeile care
iau contraceptive orale219, cu posibilul efect de a fuma
compensator.
4.2.2 Doza i tipul
Riscul asociat fumatului este n primul rnd legat de
cantitatea de tutun consumat pe zi, cu o relaie clar doz-efect fr a exista o limit inferioar a efectelor nocive220. Durata, de asemenea, joac un rol i, n
timp ce fumatul igaretelor este cel mai ntlnit, toate
tipurile de tutun fumat, inclusiv tutunul cu un coninut
redus de gudron (uoare sau medii), igarete cu filtru, trabucuri i pipe sunt duntoare211. Fumatul este
nociv, indiferent de modul n care este administrat, inclusiv narghileaua221,222. Fumul de tutun este mai nociv
prin inhalare, dar fumtorii care pretind c nu inhaleaz (de ex. fumtorii de pipe) au, de asemenea, un risc
crescut de BCV211,220. De asemenea, i tutunul care nu
se fumeaz se asociaz cu un risc mic, dar semnificativ
statistic, de cretere a riscului de infarct miocardic i
accident vascular cerebral223.
4.2.3 Fumatul pasiv
Dovezile acumulate arat c fumatul pasiv crete
riscul de cardiopatie ischemic, cu un risc relativ mai
mare dect s-ar fi ateptat209,224,225. Un nefumtor care
convieuiete cu un so fumtor are un risc de aproximativ 30% mai mare de BCV224, iar expunerea la locul
de munc este asociat cu un risc suplimentar similar226. Avnd n vedere incidena ridicat a cardiopatiei ischemice i a expunerii pe scar larg la fumul de
tutun din mediul ambiant, este de ateptat c reducerea fumului de tutun din mediul ambiant va aduce un
mare beneficiu pentru sntate. ntr-adevr, interzicerea recent a fumatului n locurile publice n diferite
zone geografice a condus la o scdere semnificativ a
incidenei infarctului miocardic210. Astfel, expunerea la
fumul de tutun din mediul nconjurtor ar trebui s fie
redus la minimum, att la persoanele asimptomatice,
ct i la cele cu cardiopatie ischemic.
4.2.4 Mecanismul prin care fumatul crete riscul
Dei mecanismele exacte prin care fumatul crete
riscul de boal aterosclerotic nu sunt pe deplin n-

Vol. 24, No. 4, 2014
elese, este clar c fumatul intervine att n dezvoltarea

aterosclerozei ct i n apariia fenomenelor trombotice
asociate acesteia. Prin studii observaionale de cohort,
observaii experimentale i studii de laborator efectuate
pe oameni i animale225,227-229, au fost elucidate mecanisme care orienteaz spre efectele fumatului asupra funciei endoteliale230,231, proceselor oxidative232, funciei
plachetare233, fibrinolizei, inflamaiei234-238, alterarrii
lipidelor i a funciei vasomotorii. Speciile reactive de
oxigen -radicalii liberi- prezeni n fumul inhalat conduc la oxidarea particulelor de LDL din plasm; particulele LDL oxidate declaneaz procesul inflamator
la nivelul intimei arterelor prin stimularea adeziunii
monocitare la peretele vasului, rezultnd progresia aterosclerozei232,239-242. n studiile experimentale, cteva din
aceste efecte sunt reversibile, total sau parial, ntr-un
timp foarte scurt243,244. Un rspuns bifazic la ncetarea
fumatului n ceea ce privete riscul de BCV este astfel
superpozabil cu efectul dual al fumatului - un efect acut
i reversibil asupra hemostazei i stabilitaii plcii i un
alt efect mai prelungit asura formrii plcii. Formarea
plcii nu este considerat a fi complet reversibil i, astfel, nu este de ateptat ca fumtorii s ajung la acelai
risc de BCV ca i cel al unui nefumtor. Cele mai recente dovezi sugereaz c expunerea la nicotin datorit
fumatului, are doar efecte minore asupra procesului de
ateroscleroza227,245 i nlocuirea nicotinei nu a avut efecte asupra evoluiei pacienilor cu boli cardiace246,247.
4.2.5 Renunarea la fumat
Beneficiile renunrii la fumat au fost raportate la
scar larg1,37,248. Unele dintre avantaje apar aproape
imediat, altele mai trziu. Studiile efectuate pe subiecii
fr BCV au artat c riscul la fotii fumtori este moderat, ntre fumtori i nefumtori248. Oprirea fumatului dup un infarct miocardic este probabil cea mai
eficient metod de prevenie: un review efectuat i o
meta-analiz a 20 de studii de cohort referitoare la renunarea la fumat dup infarctul miocardic, au artat
un beneficiu privind mortalitatea de 0,64 [95% interval
de ncredere (CI) 0,58-0,71] comparativ cu cei care au
continuat s fumeze249. Beneficiul referitor la mortalitate s-a meninut n ceea ce privete sexul, perioada de
urmrire, locaia i momentul efecturii studiului. Riscul s-a redus rapid dup ncetarea fumatului , cu reducerea semnificativ a morbiditii raportat la 6 luni250.
i datele din trialuri randomizate susin efectul benefic
al renunrii la fumat251,252. Alte dovezi arat c riscul de
BCV se apropie de cel al nefumtorilor n aproximativ
10-15 ani, fr a mai atinge ns acelai nivel248. Reducerea fumatului nu poate fi n general recomandat ca o

alternativ la renunarea la fumat, din cauza fumatului

compensator pentru a evita simptomele de abstinen
la nicotin, ducnd la o reducere mai sczut dect s-a
anticipat, disproporionat, a efectelor nocive. Nu s-a
dovedit c reducerea fumatului crete probabilitatea de
renunare la fumat n viitor, dar unii agreaz reducerea
asistat de nicotin la fumtorii care nu pot sau nu doresc sa renune11,253.
Renunarea trebuie s fie ncurajat la toi fumtorii
(Tabelul 9). Nu exist nicio limit de vrst pentru beneficiile renunrii la fumat. Nefumtorii cu risc nalt si
pacienii cu BCV stabilit ar trebui s fie sftuii n legtur cu efectele fumatului pasiv i s li se recomande
evitarea expunerii. Msurile de sntate public, cum
ar fi interzicerea fumatului, accizele la tutun i campaniile mass-media reprezint o susinere eficient n
prevenirea fumatului, informarea i sprijinirea renunrii la fumat.
Tabelul 9. Cei Cinci A pentru o strategie de ncetare a fumatului n
practica medical de rutin
A-SK (ntrebai)
ntrebai sistematic despre statusul de fumtor cu fiecare ocazie.
A-ADVISE (sftuii)
Sftuii ferm toi fumtorii s renune la fumat.
A-ASSESS (evaluai)
Determinai gradul de dependen i disponibilitatea de a renuna la
fumat pentru fiecare individ n parte.
A-ASSIST (asistai)
Stabilii mpreun strategia de renunare la fumat, incluznd
stabilirea unui termen pentru a renuna, consiliere comportamental
i suport farmacologic.
A-ARRANGE (stabilii) Stabilii un program de evaluare periodic
Terapii pentru renunarea la fumat

Renunarea la fumat este un proces complex i dificil deoarece obiceiul creeaz o puternic dependen
farmacologic i psihologic. Cel mai important factor predictiv pentru succesul renunrii la fumat, este
motivaia, care poate fi susinut cu ajutor profesionist. Sfatul ferm i explicit al doctorului, c persoana
trebuie s opreasc definitiv fumatul, este important n
iniierea procesului de ncetare a fumatului i i crete
rata de success (OR 1,66, 95% CI 1,42-1,94)225,254. Momentul ncetrii fumatului este mai ales important la
momentul diagnosticrii BCV care necesit un tratament invaziv precum CABG, PCI sau chirurgie cardiac. Aprecierea disponibilitii persoanelor de a renuna
la fumat, scurta reexpunere a riscurilor cardio-vasculare i a altor influene negative asupra sntii i convenirea asupra unui plan specific cu reevaluare periodic, sunt primii pai decisivi a unui sfat iniial concis n
practica clinic (Figura 7).
ncetarea fumatului pe perioada spitalizrii ar trebui
s continue pe o perioad ndelungat dup externare
pentru a crete rata succesului255. Un istoric al fuma

tului, incluznd consumul zilnic de igri i gradul de

dependen (cel mai frecvent apreciat prin testul Fagerstrm256), ar trebui s indice gradul de suport i ajutor
farmacologic. Fumtorii trebuie ntiiai n privina
unei posibile creteri ponderale n medie cu 5 kg, dar i
asupra faptului c beneficiile renunrii la fumat asupra
sntii depesc cu mult riscurile datorate creterii n
greutate.
4.2.6 Intervenii farmacologice
Majoritatea fumtorilor renun fr ajutor. Cu toate acestea, asistena farmacologic imbuntete substanial rata de succes. n consecin, adiional sfatului
i ncurajrilor, terapia de substituie cu nicotin (NRT),

Vol. 24, No. 4, 2014
i n unele cazuri, vareniclin sau bupropion, ar trebui

folosite n asistarea ncetrii fumatului. NRT, vareniclin sau bupropion ar trebui s fie prescrise n mod curent ca parte a unui tratament suportiv al abstinenei, n
care fumtorul i ia angajamentul de a nceta fumatul
la o anumit dat253. NRT sub form de gum de mestecat, patch-uri transdermale cu nicotin, spray nazal,
inhalator i tablete sublinguale, au fost folosite pe scar
larg pentru a ajuta fumtorii n primele sptmni sau
luni mai dificile de la ncetarea fumatului225. Toate formele disponibile de NRT sunt eficiente: ntr-o recenzie
sistematic, OR pentru abstinena cu NRT vs. Control
a fost 1,58 (95% IC 1,50-1,66)213. Folosirea patch-urilor
cu nicotin a fost testat cu succes, fr efecte adverse,
Figura 7. Altgoritm de renunare la fumat, modificat dup Organizaia Mondial a Sntii.


Vol. 24, No. 4, 2014
la pacieni care au boal coronarian257. Antidepresivul

bupropion ajut la renunarea la fumat pe termen lung,
cu eficacitate similar cu NRT. O meta-analiz a 36 de
trialuri, n care se compar rata de renunare la fumat
pe termen lung folosind bupropion vs. Control, a generat o rat relativ de succes de 1,69 (95 IC 1,53-1,85),
ns au existat dovezi insuficiente cu privire la un efect
aditiv a asocierii bupropionului la NRT258.
Agonistul parial al receptorului de nicotin, vareniclina, s-a dovedit a crete de dou sau trei ori ansa renunrii cu succes la fumat pe termen lung, comparativ
cu renunarea fr asisten farmacologic, inclusiv la
pacienii cu BCV259,260. Trialurile sugereaz un beneficiu modest al vareniclinei asupra NRT i bupropionului258,261. Efectele adverse sunt rare, dar datorit legturii cu efecte adverse severe, inclusiv depresive, agitaie
i gnduri suicidale, ar trebui evaluat istoricul psihiatric i riscul suicidal al pacientului, naintea prescrierii. Prezena morbiditilor i a simptomelor depresive
sugereaz consilierea cu privire la renunarea la fumat
i amnarea prescrierii de alte medicamente, n afar
de NRT. O meta-analiz bazat pe 14 RCT-uri incluznd 8216 pacieni, a indicat o mic, dar semnificativ cretere a riscului de evenimente cardiovasculare,
asociat cu utilizarea vareniclinei262. Ulterior, European Medicines Agency a anunat c riscul uor crescut
de evenimente cardiovasculare asociat cu vareniclina,
nu depete beneficiile medicamentului pentru sprijinirea pacienilor s renune la fumat263. Cytisina, un
agonist parial al receptorului de nicotin, cu un pre
redus, disponibil n unele ri europene, pare de asemenea s creasc ansa de renunare la fumat, dar pn n
prezent dovezile nu sunt concludente264.
Antidepresivul nortriptylina i medicamentul antihipertensiv, clonidina, ajut la ncetarea fumatului258,265,
dar, datorit efectelor adverse, reprezint alegerea de a
doua linie. Toate terapiile farmacologice pentru ncetarea fumatului ar trebui s fie utilizate pe termen scurt,
deoarece lipsesc date privind sigurana i eficacitatea pe
termen lung.
4.2.7 Alte intervenii n vederea ntreruperii
fumatului
Att interveniile individuale, ct i cele de grup, sunt
eficiente pentru ajutarea renunrii la fumat225,266-268. Suportul din partea partenerului i a familiei este foarte important. Convingerea altor membri fumtori ai
familiei s renune la fumat odat cu pacientul, este
de mare ajutor. Doctorii i persoanele care-i ngrijesc
trebuie s ofere un exemplu prin a nu fuma. Nu exist dovezi consistente c acupunctura, presopunctura,
terapia laser, hipnoterapia sau electrostimularea sunt

eficiente pentru ncetarea fumatului269.
Noi dovezi despre efectele fumatului pasiv, asupra sntii, ntresc recomandrile asupra fumatului pasiv.
Lacune rmase
Msuri mai eficiente, mai sigure i cost-eficiente
pentru renunarea la fumat.
4.3 Nutriia
Mesaje cheie
O diet sntoas are urmtoarele caracteristici:
Acizii grai saturai s reprezinte mai puin de 10% din aportul energetic total, prin nlocuirea
lor cu acizi grai polinesaturai.
Acizi grai trans-nesaturai: ct mai puini posibil, preferabil s nu provin din alimente
procesate, i <1% din totalul aportului energetic de origine natural.
<5 g de sare pe zi.
30-45 g de fibre pe zi, din cereale integrale, fructe i legume.
200 g de fructe pe zi ( 2-3 porii)
200 g de legume pe zi (2-3 porii)
Pete cel puin de 2 ori pe sptmn, dintre care o porie s fie de pete gras.
Consumul de buturi alcoolice ar trebui s fie limitat la dou pahare pe zi (20 g/zi de alcool)
pentru brbai i un pahar pe zi (10 g/zi de alcool) pentru femei.
Aportul energetic trebuie limitat la cantitatea de

energie necesar pentru meninerea (sau obinerea) unei greuti sntoase, adic un IMC
<25 kg/m2.
n general, cnd se aplic regulile pentru o diet
sntoas, nu sunt necesare suplimente dietetice.
Recomandri privind nutriia

Recomandri
O diet sntoas este recomandat ca fiind esenial
pentru prevenia BCV.
Clasaa
I
Nivelb GRADE
B
Refc
Puternic 270-276
BCV=boli cardiovasculare
a
b
Nivel de recomandare
c
Referine
4.3.1 Introducere
Se cunoate c obiceiurile alimentare influeneaz
riscul cardiovascular, avnd att un efect asupra factorilor de risc precum, colesterolul seric, TA, greutate
i diabet, ct i un efect independent de aceti factori.
O diet sntoas reduce, de asemenea, i riscul altor
afeciuni cronice, precum cancerul. Majoritatea dovezilor care certific relaia dintre alimentaie si bolile
cardiovasculare sunt bazate pe studii observaionale.
Impactul dietei poate fi studiat la diferite nivele. Cel
mai detaliat mod este de a realiza cercetri la nivelul

nutrienilor specifici. Cercetrile efectuate la nivelul

alimentelor sau grupurilor de alimente, reprezint un
alt mod de a evalua dieta, care este mai uor de integrat
n recomandrile de diet. Exist un interes n cretere
n ceea ce privete obiceiurile alimentare, dieta Mediteranean fiind cea mai studiat. Abordarea obiceiurilor
alimentare poate fi privit ca i un echivalent de trecere
de la evaluarea factorilor de risc individuali, la evaluarea profilului riscului total. O publicaie recent a EHN
ofer o vedere de ansamblu a dietei i bolilor cardiovasculare277.
4.3.2 Nutrienii
Nutrienii importani n ceea ce privete bolile cardiovasculare sunt acizii grai (care afectez n principal
nivelul lipoproteinelor), mineralele (care afecteaz n
principal TA), vitaminele i fibrele.
4.3.2.1 Acizii grai
Coninutul de grsimi i acizi grai a fost n centrul
ateniei nc din 1950, n ceea ce privete profilaxia bolilor cardiovasculare prin schimbri ale dietei. n profilaxie, coninutul n acizi grai ai dietei, este mai important dect compoziia total n grsimi. Cunotiinele
noastre despre efectele subclaselor de acizi grai (saturai, mononesaturai sau polinesaturai), precum i
despre efectele acizilor grai specifici (n-3 i acizii grai
trans), asupra diferitelor fraciuni de lipoproteine din
snge, s-au mbuntit considerabil.
Acizii grai saturai
n 1965, Keys i colab.278 au descris cum nlocuind
n diet acizii grai saturai cu acizi grai nesaturai,
s-a sczut nivelul colesterolului total. Avnd in vedere
efectul asupra nivelului colesterolului, este plauzibil un
impact asupra apariiei bolilor cardiovasculare. Totui,
dup mai mult de 40 de ani de cercetare, impactul consumului de acizi grai saturai asupra incidenei bolilor
cardiovasculare este n continuare dezbtut. Recent,
o meta-analiz a unor studii de cohort, nu a artat o
cretere a riscului relativ pentru bolile cardiovasculare
sau pentru cardiopatia ischemic la cei cu un consum
mai mare de acizi grai saturai279, chiar dac ar putea
fi mai multe precizri metodologice care ar putea explica aceste concluzii280. Anumite studii au ajustat efectul
acizilor grai saturai asupra bolilor cardiovasculare
pentru nivelurile de colesterol. Un alt aspect important,
este acela de a stabili care nutrieni vor nlocui acizii
grai saturai. Studiile epidemiologice, clinice, care s-au
concentrat asupra mecanismelor, relev rezulate concordante, conform crora, riscul pentru cardiopatia is

Vol. 24, No. 4, 2014
chemic este redus cu 2-3% atunci cnd 1% din energia

primit de la acizii grai saturai este nlocuit de acizi
grai polinesaturai, ns nu este clarificat nlocuirea
cu carbohidrai i acizi grai mononesaturai270. Prin
urmare, scderea aportului de acizi grai saturai pn
la maxim 10% din energie, prin nlocuirea cu acizi grai
polinesaturai, rmne important pentru prevenirea
bolilor cardiovasculare prin diet.
Acizii grai nesaturai
Acizii grai mononesaturai au un efect favorabil
asupra nivelului HDL-colesterolului atunci cnd ei nlocuiesc acizii grai saturai sau carbohidraii din diet281. Acizii grai polinesaturai scad nivelul de LDL-colesterol i cresc n mai mic msur nivelul HDL-colesterol, atunci cnd ei nlocuiesc acizii grai saturai. Acizii grai polinesaturai pot fi n mare divizai n dou
subgrupuri: acizi grai n-6, provenind n principal din
plante, i acizi grai n-3, care se gsesc n uleiurile de
pete i grsime. Sunt importani acizii grai eicosapentaenoic i docosahexaenoic, reprezentani ai grupului
n-3 de acizi grai. Ei nu influeneaz nivelul colesterolului seric, dar s-a dovedit c scad mortalitatea de cauz
ischemic i ntr-o mai mic msur pe cea cauzat de
accidentul vascular271,282. n diverse studii, dozele mici
de acizi grai eicosapentaenoic si docosahexaenoic sunt
asociate cu scderea riscului fatal de cauz ischemic,
dar nu i a celui non-fatal. O ipotez pentru acest efect
diferit, este c ei ar putea preveni aritmiile fatale cardiace271.
Subclasa acizilor grai nesaturai cu aa-numita
configuraie trans, acizii grai trans, s-a dovedit a
crete colesterolul total i a scdea nivelul HDL colesterol. Aceti acizi grai se gsesc n margarin i produsele de panificaie. Industria alimentar a eliminat
o parte din acizi grai trans din produse, dar se poate
ctiga i mai mult dac se elimin i alte produse. O
cantitate mic de acizi grai trans vor continua s rmn n diet, venind de la grasimea din lactate i produsele din carne. nlocuind 1% din energia provenit
de la acizii trans cu acizi saturai, mononesaturai sau
polinesaturai va scdea nivelul raportului colesterol
total/HDL colesterol cu 0,31, 0,54 i respectiv 0,67283.
O meta-analiz a unor studii prospective a artat c, n
medie, o cretere a consumului de acizi grai trans mai
mare de 2% din energie, determin creterea riscului de
cardiopatie ischemic cu 23%272. Este recomandat s se
obin <1% din totalul energetic, din consumul de acizi
grai trans, cu ct mai puin cu att mai bine.

Vol. 24, No. 4, 2014
Colesterolul din diet

Impactul colesterolului provenit din diet asupra
nivelului colesterolului total este sczut, compartiv cu
aportul acizilor grai din diet. Atunci cnd se urmrete o reducere a consumului de grsimi saturate conform ghidurilor,acest lucru duce de obicei i la o scdere a aportului de colesterol provenit din diet. Unele
ghiduri (inclusiv acesta) despre o diet sntoas, nu
specific clar date despre aportul de colesterol, iar altele
recomand un aport limitat la <300 mg/zi.
4.3.2.2 Mineralele
Sodiul
Efectul aportului de sodiu asupra TA este bine stabilit. O meta-analiz estimeaz c, o reducere a consumului de sodiu chiar cu numai 1 g/zi, reduce TAS
cu 3,1 mmHg la pacienii hipertensivi i cu 1,6 mmHg
la normotensivi284. Trialul DASH a aratat relaia dozrspuns ntre reducerea aportului de sodiu i reducerea
TA285. n cele mai multe ri vestice, consumul de sare
este mare (aprox 9-10 g/zi), n timp ce recomandrile sunt de 5 g/zi1. Nivelul optim de consum este mai
mic de 3 g/zi. Alimentele procesate sunt o important
surs de sodiu. Un studiu recent de simulare estimeaz
pentru SUA c o reducere a consumului de sare cu 3
g/zi ar duce la o reducere cu 5,9-9,6% a incideei bolilor cardiace ischemice (estimrile mai sczute sau mai
crescute se bazeaz pe diferite ipoteze), o reducere cu
5,0-7,8% a incidenei accidentului vascular i o reducere a mortalitii de orice cauz cu 2,6-4,1%286.
Potasiul
Potasiul este un alt mineral care influeneaz TA.
Principalele surse de potasiu sunt fructele i legumele.
S-a demonstrat c un consum mai mare de potasiu reduce TA. Riscul de accident vascular cerebral variaz n
funcie de aportul de potasiu: riscul relativ de accident
vascular cerebral asociat cu cea mai mare cantitate de
potasiu consumat (o medie de 110 mmoli/zi), este cu
aproape 40% mai mic dect cel asociat cu cea mai mic
cantitate de potasiu consumat (o medie de 61 mmoli/
zi)287.
4.3.2.3 Vitaminele
Vitaminele A i E
n multe cazuri i studii prospective observaionale
s-a observat o asociere invers ntre nivelele de vitamine A i E i riscul cardiovascular. Acest efect protector
a fost atribuit proprietilor antioxidante. Totui, studiile intervenionale, gndite pentru a demonstra aceast

relaie de cauzalitate, au euat n a confirma rezultatele

obinute din studiile observaionale288.
Vitaminele B (B6, acidul folic i B12) i homocisteina
Vitaminele B6, B12 i acidul folic au fost studiate
datorit potenialului lor de a scdea nivelul de homocistein, care a fost stabilit ca factor de risc pentru bolile cardiovasculare289. Totui, rmne ntrebarea dac
homocisteina este doar un factor de risc, sau face parte
dintr-o legatur de cauzalitate. Organizaia Cochrane
Collaboration a concluzionat ntr-o recent meta-analiz a 8 trialuri randomizate, c interveniile care scad
homocisteina nu reduc riscul de infarct miocardic fatal sau non-fatal (RR 1,03, 95% CI 0,94-1,13), accident
vascular cerebral (RR 0,89, 95% CI 0,73-1,08), sau mortalitatea de orice cauz (RR 1,00, 95% CI 0,92-1,09)290.
Ulterior, s-au publicat trei studii mari de prevenie secundar291-293. Toate studiile (Study of the Effectiveness of
Additional Reductions in Cholesterol and Homocysteine
(SEARCH), VITAmins TO Prevent Stroke (VITATOPS)
i Supplementation with Folate, vitamin B6 and B12
and/or OMega-3 fatty acids (SU.FOL.OM3)] au concluzionat c administrarea suplimentar de acid folic,
vitamine B6 i B12 nu ofer protecie mpotriva bolilor
cardiovasculare. Astfel, suplimentarea cu vitamine B
pentru a scdea nivelul de homocistein nu scade riscul
cardiovascular.
Vitamina D
Unele studii epidemiologice au artat existena unei
asocieri ntre deficitul de vitamin D i bolile cardiovasculare. Totui, nu exist dovezi concludente care
s arate c administrarea de suplimente de vitamina
D mbuntete prognosticul bolilor cardiovasculare,
dar exist trialuri n desfurare n acest sens294.
4.3.2.4 Fibrele
Consumul de fibre reduce riscul bolilor cardiovasculare. Chiar dac mecanismul nu este complet elucidat, se cunoate faptul c un aport crescut de fibre
reduce glicemia post-prandial dup mesele bogate n
carbohidrai i scade nivelul colesterolului total i pe cel
al LDL colesterol295. Surse importante de fibre sunt cerealele integrale, legumele, fructele i zarzavaturile. Institutul American de Medicin recomand un consum
de 3,4 g/MJ, echivalentul a 30-45 g/zi pentru aduli296.
Aceast cantitate este acceptat ca fiind optim pentru
prevenie.

4.3.3 Alimente i grupele de alimente

Fructe i legume
Studii observaionale au artat efectul protector al
consumului de fructe i legume asupra prevenirii bolilor cardiovasculare. Majoritatea dovezilor provin din
studii prospective de cohort, n timp ce trialurile randomizate sunt rare. Studiile individuale au artat efecte slabe sau nesemnificate ale consumului de fructe i
legume asupra riscului cardiovascular. Deoarece evaluarea dietelor este complex, este de ateptat s existe
erori care s duc la atenuarea unor relaii constatate.
Mai mult, pentru c se tie c persoanele care consum
multe fructe i legume difer n multe privine fa de
cei care consum puine fructe i legume (n ceea ce
privete alte obiceiuri alimentare, statusul de fumator,
nivelurile de activitate fizic) exist i alte aspecte, care
i dup ajustare rmn intricate. Cu toate acestea, rezultatele din diferite studii de cohort sunt destul de
omogene, i mai multe meta-analize au oferit estimri
statistic semnificative. Dauche i colab. au raportat o
scdere a riscului cardiovascular cu 4% (RR 0,96, 95%
CI 0,93-0,99) pentru fiecare porie n plus de fructe sau
legume consumat pe zi273. ntr-o meta-analiz alctuit din 7 studii mari prospective s-a descris o scdere de
5% a riscului de accident vascular cerebral pentru fiecare porie n plus de fructe sau legume273. He i colab.
au completat aceast estimare adugnd alte 2 grupuri
i au raportat un RR cumulat de accident vascular cerebral de 0,89 (95% CI 0,83-0,97) pentru cei care consum 3-5 porii de fructe sau legume zilnic, comparativ
cu cei care consum <3 porii, i un RR cumulat de 0,74
(95% CI 0,69-0,79) pentru cei cu un consum >5 porii
pe zi274. O porie este echivalent cu ~80 g.
Efectul protector al fructelor i legumelor pare s fie
uor mai crescut n ceea ce privete prevenirea accidentului vascular cerebral, comparativ cu prevenirea bolii
cardiace ischemice. Unul dintre motive ar putea fi efectul fructelor i legumelor asupra TA, bazat pe faptul c
ele sunt o surs important de potasiu. Trialul DASH
a artat c un consum crescut de fructe i legume a
contribuit la scderea TA observat n braul intervenional al studiului297. Alte componente ale fructelor i
legumelor, care ar putea contribui la acest efect, sunt
fibrele i antioxidanii. Recomandarea este de a mnca
cel puin 200 g de fructe (2-3 porii) i 200 g de legume
(2-3 porii) pe zi.
Petele
Efectul protector al petelui n privina bolilor cardiovasculare este atribuit cantitii de acizi grai n-3
din coninutul acestora. Calculnd riscul cumulat es

Vol. 24, No. 4, 2014
timat, s-a demonstrat c a consuma pete cel puin o

dat pe sptmn se asociaz cu o scdere de 15% a
riscului de boal cardiac ischemic (RR 0,85, 95% CI
0,76-0,96)271. O alt meta-analiz arat c un consum
de pete de 2-3 ori pe sptmn reduce riscul de accident vascular cerebral cu 18% (RR 0,82, 95% CI 0,720,94), comparativ cu cei care consum pete mai puin
de o dat pe lun282. Relaia dintre consumul de pete i
riscul cardiovascular nu este liniar. Exist o cretere
important a riscului cardiovascular pentru cei care
care nu consum deloc sau consum puin pete fa
de cei care consum moderat acest aliment. Impactul
asupra sntii publice printr-o cretere mic a consumului de pete n populaia general are un potenial
mare. O cretere a consumului de pete la 2-3 porii
pe sptmn ar reduce mortalitatea de cauz cardiac ischemic cu 36% i mortalitatea de orice cauz cu
17%298. Prin urmare, recomandarea este de a consuma
pete cel putin de dou ori pe sptmn, din care o
dat s fie pete gras.
Buturile alcoolice
Rezultatele provenite din studii epidemiologice au
artat un efect protector al consumului moderat de
alcool n apariia bolilor cardiovasculare. Relaia are
form de J, nefiind explicat de caracteristicile speciale
ale abstinenilor. Vinul rou, n special, pare s aib un
efect favorabil, care ar putea fi explicat prin efectul polifenolilor (n special resveratrol)299. Bazat pe rezultatele
unei meta-analize275, nivelul optim al consumului de alcool, n ceea ce privete mortalitatea de orice cauz, este
de aproximativ 20 g/zi pentru brbai i 10 g/zi (aproximativ echivalentul unui pahar) pentru femei. Pentru a
preveni riscul cardiovascular, aceste limite sunt ntr-o
oarecare masur destul de mari. Recomandarea este s
se limiteze consumul la un pahar de alcool/zi pentru
femei (10 g) i 2 pahare pe zi pentru brbai (20 g de
alcool) pentru a atinge cel mai sczut nivel al riscului
de boli cronice.
Buturile rcoritoare
n SUA buturile racoritoare ndulcite cu zahr reprezint cea mai mare surs de calorii provenit de la
un singur aliment i sunt, de asemenea, o surs important i n Europa. La copii i adolesceni, buturile rcoritoare reprezint 10-15% din calorii. O meta-analiz
a sugerat c pentru energia obinut dintr-o form de
lichid, compensarea aportului caloric de la mesele ulterioare, ar putea fi mai puin complet, comparativ cu
energia provenit de la alimentele solide1. Consumul
regulat de buturi racoritoare a fost asociat cu exces

Vol. 24, No. 4, 2014
ponderal i diabet zaharat tip 2300. Asemntor, consumul regulat de buturi racoritoare ndulcite cu zahr (2
porii pe zi comparativ cu una pe lun) a fost asociat cu
o cretere a riscului de cardiopatie ischemic cu 35%
la femei, chiar i dup ce s-au luat n calcul i ali factori legai de stilul de via nesntos i de alimentaie,
n timp ce buturile cu ndulcitori artificiali nu au fost
asociate cu cardiopatia ischemic301.
4.3.4 Alimente funcionale
Alimentele funcionale ce conin fitosteroli (steroli
si stanoli) sunt eficiente n scderea nivelului de LDL
colesterol cu aproximativ 10%, dac se consum n
cantitate de 2 g/zi. Efectul de scdere a colesterolului
este adiional celui obinut printr-o diet cu coninut
sczut n grsimi sau folosirii statinelor302. Unele studii recente indic faptul c, n special pentru stanoli,
dac se administreaz doze mai mari se poate obine o
scdere suplimentar a colesterolului303. nc nu exist
studii care s aib ca obiective parametrii clinici.
4.3.5 Obiceiuri alimentare
n ncercarea de a se trece de la evaluarea i tratarea
unui singur factor de risc, la a evalua profilul de risc al
unui pacient, studiile se concentreaz mai mult pe evaluarea modelelor alimentare dect a nutrienilor. Studiind n amnunt impactul unui anumit model alimentar, teoretic ar trebui s se determine ntregul potenial
de prevenie al dietei, care s cuprind o estimare combinat asupra impactului numeroaselor obiceiuri alimentare favorabile. Trialul The Seven Countries Study a
artat o diferen semnificativ n mortalitatea de cauz
cardiovascular ntre nordul i sudul Europei. Chiar i
la aceleai nivele de colesterol, dup ajustarea TA i a
fumatului, riscul s-a meninut (Figura 8)304. Dieta consumat de ctre grupurile Mediteraniene din The Seven
Countries Study este probabil un factor important care
st la baza acestor mari diferene n privina bolilor cardiovasculare ntre sudul i nordul Europei.
Conceptul de diet mediteranean cuprinde o mare
parte din nutrienii i alimentele care s-au discutat nainte: un consum mare de fructe, zarzavaturi, legume,
cereale integrale, pete, acizi grai nesaturai (un special uleiul de masline), un consum moderat de alcool (n
special vin, preferabil consumat n timpul meselor), i
un consum sczut de carne (roie), produse lactate i
acizi grai saturai.
Un numr mare de studii au demonstrat efectul protector al acestui tip de diet, i recent a fost publicat
i o meta-analiz276. Aderena la dieta mediteranean
a fost cuantificat cu ajutorul unui sistem de notare
(scor pentru dieta mediteranean) n care un punct

este obinut pentru fiecare component a dietei, acolo

unde consumul este deasupra nivelului mediu pentru
populaia studiat (fructe, legume, zarzavaturi, pete,
consum moderat de vin rou) sau sub medie (carne
roie sau gtit, produse lactate). n funcie de numrul
de tipuri de alimente, scorul putea crete de la 0 la 7-9.
Meta-analiza a artat c o aderen mai mare pentru
dieta mediteranean, cu un scor mai mare de 2 puncte,
a fost asociat cu o reducere de 10% a incidenei bolilor
cardiovasculare i a mortalitii (RR cumulat 0,90, 95%
CI 0,87-0,93) i o reducere a mortalitii de orice cauz
cu 8% (RR cumulat 0,92, 95% CI 0,90-0,94).
Concluzie
Este clar c modificrile alimentare ar trebui s reprezinte baza pentru prevenia BCV. Schimbrile din
alimentaie se vor reflecta n schimbri benefice n ceea
ce privete factorii de risc msurabili, cum sunt tensiunea arterial i nivelul colesterolului. Totui, ar trebui
reinut faptul c obiceiurile alimentare care nu au efecte
vizibile n ceea ce privete nivelul tensiunii arteriale i
al lipidelelor din snge pot contribui n mod semnificativ la prevenia BCV. Cerinele pentru o alimentaie sntoas sunt rezumate n mesajele cheie de la nceputul
acestei seciuni. Provocarea din anii urmtori va fi de a
transforma ghidurile legate de consumul de nutrieni
n diete care s fie atractive pentru oameni i de a gsi
modaliti de a-i determina pe acetia s-i schimbe
obiceiurile alimentare. Deoarece, deocamdat nu este
clar care dintre substane determin efectul protector,
se recomand o alimentaie variat, bazat pe principiile mai sus menionate. n general, n cazul adoptrii
unei diete sntoase, nu sunt necesare suplimentele,
dar cnd acestea sunt folosite, ele nu ar trebui s nlocuiasc consumul alimentelor adevrate. n ceea ce
privete unele aspecte ale alimentaiei, legislaia poate
ajuta la schimbarea compoziiei produsului de ctre
Figura 8. Rata cumulat a mortalitii prin cardiopatie ischemic la 25 de

ani, n diferite grupuri din Studiul celor apte ri, conform quartilelor
nivelului bazal al colesterolului total, ajustat n funcie de vrst, fumat i
tensiune arterial304.

sectorul industrial ( reducerea cantitii de acizi grai

trans i de sare). Industria poate contribui mult la reducerea coninutului de sare din alimentele procesate.
Cele mai importante informaii noi
Dovezile noi obinute susin opinia c homocisteina nu reprezint un factor de risc cauzator al
bolii cardiovasculare.
Sunt disponibile mai multe dovezi despre impactul dietei/obiceiuri alimentare; dieta mediteranean, mai ales, a constituit un punct de interes
tot mai mare n ultimii ani.
Lacune rmase
Cea mai mare provocare n ceea ce privete dieta
n prevenia BCV este reprezentat de dezvoltarea unor strategii mai eficiente pentru a-i determina pe oameni s-i schimbe alimentaia (att
din punct de vedere cantitativ, ct i calitativ) i
s pstreze o alimentaie sntoas i o greutate
normal.
Sunt n derulare cercetri referitoare la substanele din alimente care sunt rspunztoare de
efectul protector.
4.4 Activitatea fizic
Mesajul cheie
Participarea la activiti fizice regulate i/ sau la
antrenamet de tip aerob se asociaz cu scderea
mortalitii cardiovasculare.
4.4.1 Introducere
Activitatea fizic regulat i antrenamentul aerob
sunt legate de reducerea riscului de evenimente coronariene fatale i non-fatale la persoanele sntoase305-307,311, la subiecii cu factori de risc coronarian312 i
la pacienii cu boli cardiovasculare309,310 ntr-un interval
de vrst larg. Stilul de via sedentar reprezint unul
din factorii majori de risc pentru boala cardiovascular.313 Astfel, ghidurie sugereaz c activitatea fizic i
practicarea exerciiilor de tip aerob, sunt un instrument
non-farmaceutic foarte important pentru prevenia
cardiovascular primar i secundar37,204,314. n Uniunea European, sub 50% dintre ceteni sunt implicai
n activiti regulate de exerciiu fizic aerob n timpul
liber i/ sau n activiti care presupun activitate fizic315,316, creterea prevalenei obezitii fiind corelat cu
stilul de via sedentar317,318. Mai mult, probabil mai puin de o treime din pacienii eligibili pentru reabilitarea
cardiac sunt supui acesteia33. Astfel, exist un decalaj
important n Europa ntre aciunile de prevenie cardiovascular primar i secundar bazate pe exerciii

Vol. 24, No. 4, 2014
care se impun i msurile care se iau efectiv319, mai ales

cnd lum n calcul faptul c unele ri din Europa de
Est care au aderat de curnd la Uniunea European nregistreaz unele dintre cele mai ridicate rate ale mortalitii cauzate de boli cardiovasculare legate de vrst,
la nivel mondial320.
Recomandri privind activitatea fizic
Recomandri
Adulii sntoi de toate vrstele ar trebui s practice
sptmnal 2,5-5 ore de activitate fizic sau exerciiu
aerobic de intensitate cel
puin moderat sau 1-2,5 ore pe sptmn de
exerciiu fizic intens.
Indivizii sedentari trebuie puternic ncurajai s nceap programe de exerciii de intensitate sczut.
Activitatea fizic/ exerciiul aerobic ar trebui efectuate
n mai multe reprize, fiecare de 10 min, repartizate
uniform de-a lungul sptmnii, 4-5 zile/ sptmn.
Pacienii cu infarct miocardic acut n antecedente, CABG,
PCI, angin pectoral stabil sau insuficien cardiac
cronic ar trebui s practice exerciii aerobice de intensitate moderat spre ridicat de 3 ori/ sptmn i
30 de minute per edin.
Pacienii sedentari ar trebui s fie puternic ncurajai
s nceap programe de exerciii de intensitate uoar
dup evaluarea riscului legat de efectuarea exerciiilor.
Clasaa
Nivelb GRADE
Refc
305308
Puternic
IIa A
Puternic 305-308
Puternic
309,
310
Clasa de recomandri
Nivelul de eviden
c
Referine
a
b
4.4.2 Argumentul biologic

Activitatea fizic regulat de tip aerob are drept urmare mbuntirea performanei, aceasta depinznd
de capacitatea de a folosi oxigenul pentru a obine
energie pentru activitate. Aceste efecte sunt obinute
n cazul activitii fizice regulate aerobe la o intensitate
variind ntre 40% i 85% din VO2 [volumul maxim (V)
de oxigen (O2) n mL] sau din rezerva ritmului cardiac,
cu necesitatea creterii nivelului intensitii odat cu
creterea nivelului condiiei fizice, i invers321. Exerciiile aerobe au drept urmare i scderea necesarului de
oxigen miocardic pentru acelai nivel de activitate realizat, fapt demonstrat de scderea produsului frecven
cardiac x tensiune arterial, reducndu-se, astfel, posibilitatea apariiei ischemiei miocardice322.
n plus, perfuzia miocardic poate fi mbuntit
prin exerciii aerobe, producndu-se o cretere a diametrului interior al arterelor coronare majore, o cretere a microcirculaiei i o mbuntire a funciei endoteliale323,324. Alte efecte ale exerciiilor aerobe sunt
reprezentate de efectele antitrombotice care pot reduce
riscul de ocluzie coronarian dup ruptura unei plci
vulnerabile, efecte precum creterea volumului plas-

Vol. 24, No. 4, 2014
mei, reducerea viscozitii sngelui, scderea agregrii

plachetare i creterea capacitii trombolitice325, precum i o reducere a riscului de aritmii printr-o modulare favorabil a echilibrului autonom326.
Activitatea fizic are, de asemenea, un efect pozitiv
asupra multora dintre factorii de risc dovedii pentru
boli cardiovasculare, prevenind sau ntrziind dezvoltarea hipertensiunii la persoanele normotensive i reducnd tensiunea arterial la pacienii hipertensivi,
crete nivelul colesterolului HDL, ajut la controlul greutii corporale i scade riscul de dezvoltare a diabetului zaharat non-insulino-dependent37,311. Mai mult, s-a
artat c practicarea exerciiilor determin precondiionarea ischemic a miocardului, un proces prin care
ischemia miocardic pasager din timpul exerciiilor
crete tolerana miocardului la un stres ischemic ulterior prelungit, reducnd astfel distrugerea miocardic
i riscul unor tahiaritmii ventriculare potenial letale.
Asemenea mecanisme cardioprotectoare includ modificri anatomice ale arterelor coronare, inducia proteinelor miocardice de oc termic, creterea activitii
miocardice a ciclooxigenazei-2, creterea produciei
proteinelor de stres ale reticulului endoplasmatic i de
oxid nitric, ameliorarea funcionrii adenozin trifosfatului sarcolemal i mitocondrial (ATP)- canale de potasiu sensibile i a capacitii antioxidante miocardice,
reglarea enzimelor antioxidante cheie, i determin
schimbri n fenotipul mitocondrial, care au rol protector mpotriva stimulilor apoptotici327.
4.4.3 Persoanele sntoase
La persoanele sntoase, nivelurile crescute att ale
activitii fizice, ct i ale condiiei cardiorespiratorii
sunt asociate cu o scdere semnificativ (aproximativ
20-30%) a riscului de mortalitate cardiovascular i
de alte cauze, ntr-o relaie doz-rspuns305-308,311,328,329.
Dovezile sugereaz c riscul de deces ntr-o anumit
perioad continu s scad odat ce activitatea fizic
i cardiorespiratorie crete; acest fapt pare a fi valabil
att pentru brbai, ct i pentru femei, pentru vrste
foarte diverse, de la copii la cei foarte vrstnici. Dat fiind c aceste concluzii se sprijin pe rezultatele studiilor observaionale, eroarea de selecie poate fi legat, pe
de-o parte de existena unor boli subclinice, nediagnosticate, care ar fi putut determina persoanele s scad
nivelul activitii fizice nainte de nceperea studiului
i, pe de alt parte, de tendina de a asocia obiceiuri
mai sntoase (e.g. evitarea fumatului i adoptarea unei
diete mai sntoase) la persoanele active din punct de
vedere fizic. Totui, chiar i n studiile n care s-a fcut
corecie n funcie de aceti poteniali factori de confu-

zie s-a observat o asociere invers ntre activitatea fizic

i cardiorespiratorie i mortalitatea cardiovascular sau
din alte cauze.
Cea mai mare parte a acestui efect de reducere a
mortalitii pare a se baza pe scderea mortalitii cardiovasculare i a mortalitii cauzate de boala coronarian, iar scderea riscului coronarian atribuibil activitii fizice de tip aerobic este similar cu cel al altor factori
legai de stilul de via, precum evitarea fumatului. Riscul de boal cardiovascular (inclusiv boal coronarian i accidentul vascular cerebral) sau doar de boal coronarian este redus n mod semnificativ la persoanele
mai active din punct de vedere fizic sau antrenate, cu o
scdere de aproape dou ori a riscului relativ, reducerea
fiind mai accentuat la cei cu fitness cardiorespirator
crescut comparativ cu simpla cretere a intensitii activitii fizice, pentru toate percentilele > a 25-a308,328,329.
O posibil explicaie pentru gradientul doz-rspuns
mai bun pentru fitness dect pentru activitatea fizic
este aceea c starea de fitness este msurat obiectiv,
n timp ce activitatea fizic este evaluat prin auto-raportri care pot conduce la clasificri eronate i erori
privind o activitate fizic mai slab sau asocierea dintre
activitatea fizic i beneficiul pentru sntate.
Intensitatea i volumul activitii fizice
Volumul de activitate fizic de intensitate moderat
sau antrenament fizic aerob estimat c ar reduce mortalitatea cardiovascular sau din alt cauz este de la
2,5 la 5 h/sptmn306-308,311,312; cu ct durata total a
activitii fizice /a exerciiilor aerobe din timpul sptmnii este mai mare, cu att beneficiile observate sunt
mai mari. De remarcat faptul c rezultate similare se
obin prin activitate fizic/ exerciii aerobe de intensitate crescut (vigorous-intensity) practicate 1-1,5 h/
sptmn sau printr-o combinaie echivalent de activitate fizic/ exerciii aerobe de intensitate moderat
i crescut. Mai mult, dovezile existente sugereaz c
volumul sptmnal total de activitate fizic/ exerciii
aerobe poate fi obinut prin nsumarea mai multor reprize de exerciii zilnice, fiecare avnd o durat de 10
min, i c activitatea fizic/ exerciiile aerobe ar trebui
repartizate n majoritatea zilelor sptmnii.
Exemplele de activitate fizic/ exerciii aerobe nu implic doar activiti sportive precum drumeiile, alergatul sau joggingul, patinajul, mersul cu bicicleta, vslitul,
notul, schiul i frecventarea orelor de gimnastic aerobic, ci i activiti comune care fac parte din stilul de
via, precum mersul energic, urcatul scrilor, activitile casnice, grdinritul, implicarea n activiti recrea

tive active. O activitate fizic de intensitate moderat ar

trebui definit n termeni relativi ca o activitate desfurat la 40-59% din VO2 sau rezerva ritmului cardiac,
sau la o dificultate a efortului perceput pe scala CR10
Borg de 5-6, care ar corespunde unui consum energetic
absolut de aproximativ 4,8-7,1 echivaleni metabolici
(METs) la tineri, 4,0-5,9 METs la cei de vrst mijlocie,
3,2-4,7 METs la vrstnici i 2,0-2,9 METs la cei foarte
vrstnici140. n mod similar, activitatea fizic de intensitate ridicat se desfoar la 60-85% din VO2 sau rezerva ritmului cardiac, sau la o dificultate a efortului perceput pe scala CR10 Borg de 7-8, corespunznd unui
consum energetic absolut de 7,2-10,1 METs la tineri,
6,0-8,4 METs la cei de vrst medie, 4,8-6,7 METs la
vrstnici i 3,0-4,2 METs la cei foarte vrstnici140.
Evaluarea riscului
Metodologia potrivit creia persoanele sntoase ar
trebui evaluate naintea nceperii unei activiti fizice
regulate/ exerciiilor aerobe este controversat. n general, riscul de evenimente cardiovasculare majore legate de exerciii la persoanele aparent sntoase este extrem de mic, variind ntre 1 la 500 000 i 1 la 2 600 000
pe ore-pacient de exerciii330,331. Dup cum s-a propus
recent n cazul activitilor sportive din timpul liber
pentru persoane de vrst medie/seniori332, exactitatea
evalurii riscului ar trebui adaptat profilului de risc
cardiac al individului, nivelului real al activitii fizice
obinuite i nivelului dorit al activitii fizice / exerciiilor aerobe, cu un screening mai agresiv (testare la efort)
rezervat persoanelor sedentare i / sau cu factori de risc
cardiovascular i/ sau care doresc s se implice n activiti de intensitate mare. Persoanele care practic
exerciiu fizic doar ocazional par a avea un risc crescut
de evenimente coronariene acute i de moarte subit
cardiac n timpul exerciiilor sau dup acestea330,331. La
persoanele sedentare i la cele cu factori de risc cardiovascular, se recomand, n general, nceperea cu activiti de intensitate joas.
4.4.4 Pacienii cu boal cardiovascular
cunoscut
La pacienii cu boal cardiovascular cunoscut, activitatea fizic aerob este considerat, n mod obinuit,
ca o intervenie prin antrenament fizic n cadrul unui
program de recuperare cardiac. De aici faptul c datele
disponibile sunt aproape exclusiv cele date de msurarea nivelului de fitness cardiorespirator i nu de evaluarea nivelului de activitate fizic obinuit. Aceasta
se datoreaz nevoii de a avea o evaluare formal, att
a capacitii de efort, ct i a riscului asociat exerciiu

Vol. 24, No. 4, 2014
lui fizic la pacienii cu boal cardiac diagnosticat. n

acest context, efectele doar ale activitii fizice asupra
riscului cardiovascular s-ar putea s nu fie uor de
identificat. Totui, o meta-analiz care a inclus mai ales
brbai de vrst medie, cei mai muli avnd n antecedente un infarct miocardic acut, iar ceilali o intervenie de CABG sau PCI sau angin pectoral stabil, a
evideniat o reducere cu aproximativ 30% a mortalitii
cardiovasculare totale n cazul programelor de exerciii
aerobe cu o durat de cel puin trei luni; acest procent
a crescut la 35% cnd a fost luat n calcul doar mortalitatea cauzat de boala coronarian333. n ceea ce privete efectele exerciiilor aerobe asupra ratei revascularizrii, datele disponibile au fost insuficiente; n plus,
exerciiile aerobe nu au evideniat vreun efect asupra
apariiei infarctului miocardic non-fatal. Utilizarea mai
larg a tehnicilor de revascularizare i a tratamentelor
medicamentoase n ultimii ani a avut ca rezultat o populaie general de pacieni cardiaci cu un risc relativ
sczut, n cazul crora este mai puin probabil s survin ameliorri importante ale supravieuirii ca urmare
a vreunei intervenii. n orice caz, datele recente confirm existena unui raport inversat doz-rspuns ntre
fitness cardiovascular (evaluat prin testul de efort i exprimat n METs) i mortalitatea de orice cauz n rndul populaiilor mari cuprinznd pacieni cardiovasculari brbai i femei [cu istoric de boal coronarian documentat angiografic, infarct miocardic, CABG, PCI,
insuficien cardiac cronic, boala vascular periferic
sau semne ori simptome sugestive pentru boal coronarian la testul de efort]. Rezultatele au fost aceleai,
independent de utilizarea agenilor betablocani334,335.
n final, s-a artat c exerciiile aerobe la pacienii cu
risc sczut au fost cel puin la fel de eficiente n mbuntirea strii clinice i a perfuziei miocardice, fiind
asociate cu mai puine evenimente cardiovasculare, n
comparaie cu strategiile invazive precum PCI336.
Efectele exerciiilor aerobe asupra mortalitii cu cauz cardiac la pacienii cu insuficien cardiac cronic au fost evaluate ntr-o meta-analiz310. Per ansamblu,
exerciiile aerobe de intensitate moderat spre intens
au avut ca rezultat creterea supravieuirii la pacienii
cu insuficien cardiac cronic dat de disfuncia sistolic ventricular stng i timpul pn la respitalizare a crescut semnificativ. mbuntirea pronosticului
a fost mai ridicat la pacienii cu etiologie ischemic,
fracie de ejecie a ventriculului stng mai sczut i un
vrf al VO2 mai sczut, i aparinnd unei clase superioare NYHA. Aderena la intensitatea programului de
antrenament aerob s-a dovedit a fi un aspect esenial

Vol. 24, No. 4, 2014
pentru obinerea acestor beneficii asupra prognosticului, aa cum a fost demonstrat de rezultatele recentului
studiu HF-ACTION (Heart Failure and A Controlled
Trial Investigating Outcomes of Exercise TraiNing)337.
Intensitatea i volumul activitii fizice
La pacienii cu boal cardiovascular, datele disponibile nu permit definirea unui volum de exerciii aerobe sptmnale la fel de precis precum cel indicat
pentru subiecii sntoi309,310, prescrierea exerciiilor
trebuind adaptat profilului clinic al individului. Pacienii cu risc clinic sczut, care au antecedente de infarct
miocardic acut, CABG, PCI sau cu angin pectoral
stabil sau insuficien cardiac cronic pot fi supui
unui antrenament de exerciii aerobe de intensitate
moderat pn la ridicat de 3-5 edine pe sptmn,
30 min per edin, cu adaptarea frecvenei, duratei i
supervizrii exerciiilor aerobe n funcie de caracteristicile clinice. Pacienii cu risc moderat spre crescut ar
trebui s beneficieze de o prescriere a exerciiilor mai
strict individualizat, n funcie de ncrctura metabolic cunoscut a determina semne sau simptome.
Totui, chiar i la pacienii cu mai multe restricii, un
numr mic de activiti fizice supravegheate corespunztor este benefic pentru a permite meninerea unei
viei independente i a combate depresia dat de boal. Sunt disponibile informaii bazate pe dovezi pentru
prescrierea exerciiilor aerobe la sub-populaii specifice
de pacieni cardiaci205.
Evaluarea riscului clinic
La pacienii cu boal cardiovascular, prescrierea
exerciiilor depinde mult de riscul legat de exerciiu.
Algoritmii existeni de stratificare a riscului ajut la
identificarea pacienilor cu risc crescut pentru evenimente cardiovasculare legate de exerciiul fizic i care
pot necesita o monitorizare cardiac mai intens338,339,
iar sigurana programelor de exerciii supravegheate
medical este bine stabilit. Apariia evenimentelor cardiovasculare majore n timpul exerciiilor aerobe supravegheate n programele de reabilitare cardiac este
rar: de la 1 la 50 000 la 1 la 120 000 de ore-pacient de
exerciii, cu o inciden a deceselor variind ntre 1 la
340 000 i 1 la 750 000 de ore-pacient de exerciii340,341.
Acelai lucru este valabil i pentru pacienii cu insuficien cardiac cronic i funcie ventricular stng redus, cu simptome clasa II-IV NYHA, aflai sub
tratament optim, bazat pe dovezi, pentru insuficien
cardiac342.


n ultimii ani nu au aprut informaii noi majore n
acest domeniu.
Lacune rmase
Rmne s se stabileasc dac:
Se poate obine o mbuntire a prognosticului
cu mai puin activitate fizic (ca durat / intensitate), la grupurile la care nu se pot aplica
recomandrile (vrstnici, persoane decondiionate, pacieni cu insuficien cardiac cronic
avansat).
Relaia doz-rspuns dintre fitness cardiorespirator i reducerea riscului cardiovascular observat n prevenia primar este valabil i n cazul
preveniei secundare.
Activitatea fizic regulat aduce un beneficiu pe
termen lung legat de pronostic la pacienii cu
insuficien cardiac cronic.
Exerciiile de intensitate mare fcute n reprize
sunt superioare exerciiilor de intensitate moderat fcute continuu n ceea ce privete mbuntirea capacitii funcionale i inducerea
remodelrii favorabile a ventriculului stng la
pacienii cu insuficien cardiac cronic.
4.5 Managementul factorilor psiho-sociali
Mesaj cheie
Interveniile psihologice pot combate stresul psiho-social i pot promova o conduit sntoas i
un stil de via sntos.
Recomandri privind managementul factorilor psihosociali
Recomandri
Clasaa Nivelb GRADE Refc
Ar trebui prescrise intervenii comportamentale mul195,
timodale, educaie medical, exerciiu fizic i terapie
197I
A
Puternic
psihologic pentru
200
factorii de risc psihosociali i pentru a face fa bolii.
n cazul simptomelor clinic semnificative de depresie,
85, 86,
anxietate i ostilitate, ar trebui luate n calcul psihote199,
rapia, tratamentul medicamentos sau ambele. Aceast
200,
IIa
A
Puternic
abordare poate reduce simptomele legate de dispoziie
343i poate crete calitatea vieii, dei dovezile despre
347
efectul benefic clar asupra endpointurilor cardiace nu
sunt concludente.
a
Clasa de recomandri
b
Nivelul de eviden
c
Referine
4.5.1 Introducere
Interveniile psihologice au drept scop combaterea
stresului psiho-social i promovarea unei conduite
sntoase i a unui stil de via sntos. Interveniile includ consiliere de grup sau individual legat de

factorii de risc psiho-social i modaliti de a face fa

bolii, terapie cognitiv-comportamental, programe de
management al stresului, meditaie, training autogen,
biofeedback, exerciii de respiraie, yoga, i/ sau relaxare muscular199,200. Este probabil ca interveniile psihologice s aib i alte efecte benefice asupra factorilor
de risc i a strii de suferin, chiar i atunci cnd sunt
adugate unei reabilitri standard199. Dou meta-analize recente i dou studii randomizate controlate recente199,343,348, au evideniat, de asemenea, impactul lor
suplimentar asupra preveniei bolilor cardiovasculare,
mai ales la pacienii care au atins obiectivele comportamnetale349. Exist dovezi c programele de intervenie ar trebui individualizate n funcie de profilul de
risc individual i s includ aspecte specifice legate de
gen199,350.
4.5.2 Intervenii specifice pentru reducerea
depresiei, anxietii i strii de suferin
Mai multe studii randomizate controlate i o metaanaliz au fost ndreptate intit spre depresia pacienilor cu boal cardiovascular. Pacienii coronarieni cu
depresie semnificativ din punct de vedere clinic pot
fi tratai n siguran i eficient cu ajutorul psihoterapiei84,85,351-353 sau al inhibitorilor selectivi ai recaptrii serotoninei354-356, dei dovezile pentru efectul benefic asupra endpointurilor cardiace este neconcludent. n timp
ce, cele mai multe studii nu au putut evidenia vreun
efect benefic semnificativ84,351-356, un studiu randomizat
controlat fcut recent a demonstrat mai puine simptome depresive, ca i mai puine evenimente adverse
cardiace majore85. O analiz secundar a altui studiu
randomizat controlat a evideniat efecte cardiovasculare benefice doar la brbaii albi344, i la pacienii care au
rspuns la tratamentul antidepresiv346. Rezultatele din
studiile nerandomizate arat c inhibitorii selectivi ai
recaptrii serotoninei pot avea, de asemenea, potenialul de a ameliora pronosticul bolii cardiovasculare la
pacienii depresivi cu345 i fr347 boal cardiovascular
dovedit anterior.
Spre deosebire de depresie, pn acum doar foarte
puine studii au vizat n mod precis anxietatea la pacienii cu boal cardiovascular. Un studiu randomizat
controlat incluznd intervenii la domiciliu coordonate de asistente medicale pentru pacienii post-CABG a
evideniat efecte pozitive asupra anxietii, dar eantionul a fost prea mic i perioada de urmrire prea scurt pentru a demonstra impactul asupra evenimentelor
cardiace357.
n ateptarea rezultatelor care s demonstreze c tratarea depresiei sau a anxietii va schimba pronosticul

Vol. 24, No. 4, 2014
bolii cardiovasculare, o abordare prudent n prezent

este reprezentat de oferirea de psihoterapie i tratament antidepresiv/ anxiolitic medicamentos pentru
pacienii cu depresie semnificativ din punct de vedere
clinic. Cei care nu accept tratament ar trebui monitorizai atent i tratai din nou dac simptomele persist
mai mult de 4-6 sptmni.
n afara tratamentului pentru simptomele legate de
dispoziie, exist i alte abordri de intervenie psihosocial care s-au dovedit utile. S-a evideniat n mod
repetat c programele de management al stresului mbuntesc nu numai starea de bine subiectiv, ci i
nivelurile factorilor de risc i evoluia bolii cardiovasculare199,200,358. La pacienii ostili cu boal cardiac coronarian, o intervenie de control a ostilitii ar putea
conduce nu numai la scderea ostilitii, ci i la scderea depresiei, frecvenei cardiace de repaus i a reactivitii cardiovasculare la stresul mental, ca i la creterea suportului social i a gradului de satisfacie fa
de via359,360. Pentru femei, pot fi utile tratamente comportamentale specifice de grup pentru reducerea strii
de suferin348,350,361. Recent, un program de reducere a
stresului bazat pe grup la persoanele de sex feminin, a
evideniat o prelungire a vieii independent de ali factori de pronostic348,358.
Reorganizarea muncii orientat spre creterea autonomiei i a controlului la locul de munc poate avea
drept rezultat mbuntirea suportului social i reducerea reaciilor la stresul fiziologic. Prin urmare, reducerea stresului legat de munc la manageri i la supervizori poate avea efecte benefice asupra sntii i poate
mbunti suportul social perceput de subordonai362.
Exist tot mai multe dovezi c interveniile psihologice combat stresul psiho-social, promoveaz
conduite sntoase i contribuie la prevenirea
bolii cardiovasculare.
Lacune rmase
Dovezile c tratamentul depresiei i anxietii
semnificative clinic va mbunti endpointurile
cardiace sunt neconcludente.
4.6 Greutatea corporal
Mesaje cheie
Att excesul ponderal, ct i obezitatea sunt asociate cu riscul de deces n boala cardiovascular363-365.
Exist o asociere pozitiv linear a indicelui de
mas corporal (IMC) cu mortalitatea general363.


Vol. 24, No. 4, 2014
Mortalitatea general este cea mai sczut atunci

cnd IMC este de 20-25 kg/m2 363-365.
Scderea greutii sub aceast limit nu poate
fi considerat ca avnd rol protector mpotriva
bolii cardiovasculare366-369.
Recomandri privind greutatea corporal

Recomandri
Clasaa
Se recomand scderea n greutate pentru persoanele
supraponderale i obeze, deoarece se asociaz cu
efecte favorabile asupra tensiunii arteriale i a dislipiI
demiei, care ar putea duce la scderea BCV.
a
b
c
Nivelb GRADE
Puternic
Refc
363365
Clasa de recomandri
Nivelul de eviden
Referine
4.6.1 Introducere
n multe ri, o scdere a factorilor de risc major precum hipercolesterolemia i hipertensiunea i, mai recent, a fumatului a fost corelat cu reducerea mortalitii de cauz cardiovascular. Excepiile de la aceste tendine sunt greutatea corporal i diabetul, care au avut
tendina s creasc pe msur ce ali factori de risc au
sczut. Obezitatea devine o epidemie la nivel mondial
att la aduli, ct i la copii370. Scenariul s-a schimbat
ntr-o asemenea msur nct n S.U.A., dac direciile
n ceea ce privete obezitatea vor continua neschimbate
din 2005 pn n 2020, obezitatea va depi din ce n ce
mai mult efectele pozitive ale scderii fumatului371. n
Europa, un studiu recent cu aproape 360 000 de participani din nou ri europene a artat c obezitatea general i adipozitatea abdominal sunt ambele asociate
cu risc crescut de deces372.
4.6.2 Greutatea corporal i riscul
Este acum clar c una din componentele grsimii
abdominale, esutul adipos visceral, este un organ endocrin activ, capabil s sintetizeze i s elibereze n
fluxul sanguin o varietate important de peptide i de
compui non-peptidici care ar putea avea un rol n homeostazia cardiovascular373. Acest proces are efect
asupra factorilor de risc pentru BCV i de aici asupra
riscului, efectele mecanice ale supraponderabilitii
avnd efect asupra cauzelor non-cardiovasculare ale
morbiditii i mortalitii. Efectele greutii corporale
crescute asupra sntii sunt rezumate n Tabelul 10.
Este interesant faptul c dup ajustatrea multivariabil
efectele asocierii dintre nivelul lipidelor i risc i dintre
greutatea corporal i risc sunt diferite. Nivelurile ridicate ale colesterolului din snge i nivelurile sczute
ale colesterolului HDL rmn independent asociate cu
riscul dup reglarea altor factori de risc major, n timp
ce corelarea dintre greutate i risc tinde s-i piard din

importan. Acest aspect nu ar trebui interpretat ca un
indicator al faptului c greutatea corporal nu este important; mai degrab, ea poate fi esenial pentru c
influeneaz riscul prin efectele adverse pe care le are
asupra multor factori de risc.
Tabelul 10. Potenialele efecte adverse cardiovasculare ale greutii
corporale crescute
Creterea rezistenei la insulin (intoleran la glucoz, diabet zaharat de tip 2).
Creterea tensiunii arteriale
Creterea inflamaiei sistemice i stare protrombotic.
Albuminurie.
Dislipidemie (niveluri crescute ale colesterolului total, LDL colesterol, non-HDL colesterol,
trigliceridelor, apolipoproteinei B, particulelor mici i dense de LDL, niveluri sczute ale HDL
colesterol, apolipoproteina A1).
Anomalii cardiovasculare i cerebrovasculare (disfuncie endotelial, insuficien cardiac,
boal coronarian, fibrilaie artial, accident vascular cerebral, geometrie ventricular stng
anormal, disfuncie sistolic i diastolic, activitate simpatic ridicat).
HDL = lipoprotein cu densitate nalt; LDL = lipoprotein cu densitate mic.
4.6.3 Care indice de obezitate este cel mai bun

predictor al riscului cardiovascular?
Indicele de mas corporal [greutatea (kg)/nlimea
(m)2] a fost utilizat pe scar larg pentru a defini categoriile greutii corporale. La aduli, supraponderabilitatea este definit de un IMC variind ntre 25 i 29,9
kg/m2, i obezitatea de un IMC 30 kg/m2. IMC crescut
este puternic asociat cu riscul de boal cardiovascular.
Totui, exist ipoteza c repartizarea pe zone a esutului adipos este mai important n determinarea riscului
cardiovascular dect greutatea corporal total. Acest
fapt a contribuit la creterea interesului pentru msurtori antropometrice ale riscului i pentru o repartizare mai precis a masei grase i a masei slabe (Tabelul
11). Cele mai multe date sunt disponibile pentru IMC,
raportul talie: circumferina oldului i simpla circumferin a taliei. Locul optim pentru msurarea circumferinei taliei este la mijlocul distanei dintre marginea
inferioar a coastelor i creasta iliac superioar anterioar, n ortostatism. Pragurile WHO374 pentru circumferina taliei sunt acceptate n cea mai mare parte a
Europei; se recomand dou praguri de aciune:
Pragul 1circumferina taliei 94 cm la brbai
i 80 cm la femei reprezint pragul peste care
nu ar trebui s mai existe o cretere suplimentar
n greutate.
Pragul 2circumferina taliei 102 cm la brbai
i 88 cm la femei reprezint pragul la care se
recomand reducerea greutii.
Aceste praguri au fost calculate plecnd de la populaia caucazian i sunt necesare puncte-limit diferite

pentru msurtori antropometrice la rase i etnii diferite.

Cteva studii prospective au demonstrat asocieri mai
puternice ale mrimii adipozitii abdominale cu boala
cardiac coronarian dect IMC sau cu boala cardiac
coronarian la femei375,376, dar nu i la brbai; aceste
studii au fost n general studii mici. Un studiu amplu
caz-control a evideniat c raportul talie:old a fost asociat mai mult cu infarctul miocardic dect IMC, att la
femei, ct i la brbai377.
Tabelul 11. Tipuri de msurtori ale obezitii generale i ale adipozitii abdominale
Msurtori ale obezitii generale
Indicele de mas corporal
Msurtori ale adipozitii abdominale
Circumferina taliei
Raportul talie:old
Raportul talie:nlime
Msurtori directe ale masei de grsime
Analiza impedanei bioelectrice
Grosimea pliului cutanat
Msurtori ale obezitii generale i ale adipozitii abdominale
Absorbiometrie dual cu raze X
Ecografie
Tomografia computerizat
Imagistic pentru rezonan magnetic
Este posibil ca circumferina taliei s fie mai puternic asociat cu diabetul dect IMC la femei, dar nu i
la brbai. O meta-analiz recent a 32 de studii nu a
evideniat nicio diferen ntre IMC, circumferina taliei i raportul talie:old n asocierea lor cu incidena
diabetului378, i nu a artat diferene importante ntre sexe. Totui, autorii nu au putut investiga lipsa de
omogenitate n rezultatele legate de sex dect limitat,
dat fiind numrul mic de studii n fiecare grup. Rezultatele recente din Prospective Studies Collaboration363,
incluznd peste 900 000 de participani au evideniat
asocieri pozitive liniare ale IMC de la 22,5 la 25,0 cu
mortalitatea general.
ntr-o analiz combinat a 19 studii prospective
(1,46 milioane de aduli albi)364, mortalitatea general a
fost cea mai sczut la indivizii cu IMC de 20,0-24,9. La
o populaie asiatic, (1,1 milioane de oameni recrutai
n 19 cohorte)365, cel mai mic risc de deces a fost ntlnit
n cazul IMC ntre 22,6-27,5. Riscul a fost crescut n
cazul IMC fie mai mari, fie mai mici dect acest interval, ntr-o asociere n forma de U. Rezultatele acestui
studiu, ct i a altor studii precedente fcute n Europa,
potrivit crora acelai IMC optim se coreleaz cu cel
mai mic risc de deces, contrazice folosirea de cut-off
points IMC pentru ras sau etnie pentru definirea supraponderabilitii i obezitii363.

Vol. 24, No. 4, 2014
n studiul de cohort European Prospective Investigation into Cancer and Nutrition (EPIC), IMC, circumferina taliei i raportul talie:old au fost toate asociate
independent cu mortalitatea general; autorii au recomandat utilizarea circumferinei taliei sau a raportului
talie:old n plus fa de IMC pentru evaluarea riscului
de deces; totui, nu au fost fcute comparaii directe ntre importana asocierilor dintre diferite msurtori372.
Datele sunt comparabile cu rezultatele a patru studii
de cohort la aduli: British Womens Heart and Health
Study, Caerphilly Prospective Study, Boyd Orr Study i
MaidstoneDewsbury Study379. Datele din aceste studii
explic asocierile uor mai mari ale adipozitii centrale cu mortalitatea general prin cauzalitatea invers,
care este posibil s afecteze IMC (din cauza slbirii generale a masei musculare totale i a pierderii grsimii)
mai mult dect adipozitatea380.
Plecnd de la dovezile referitoare la exactitatea i sigurana mai slab a msurrii circumferinei taliei i a
oldului381-383, nu este posibil ca aceste msurtori ale
adipozitii viscerale s fie considerate ca alternative ale
IMC n practica de rutin; este de asemenea de remarcat faptul c IMC nu a fost un predictor mai puternic
al prognosticului dect au fost alte msurtori, n timp
ce msurarea obezitii centrale a avut corelaii ceva
mai puternice cu mortalitatea general i diabetul de
tip 2. O alt ntrebare este dac msurtorile regionale
ale adipozitii ar aduga valoare capacitii predictive
a IMC pentru identificarea celor cu risc de boal cardiovascular viitoare. Pe de alt parte, cerina pentru
msurtori mai directe ale masei de grsime, precum
cea prin analiza impedanei bioelectrice sau utilizarea
grosimii pliului cutanat, pot fi problematice n practica
clinic i de sntate public de rutin din cauza dificultilor legate de msurtori exacte i sigure383-386. Au
fost descrise mai multe msurtori pentru evaluarea
distribuiei anatomice a grsimii, precum tomografia
computerizat, ecografia (mai ales la nivel epicardic),
absorbiometria dual cu raze X i imagistica prin rezonan magnetic. Toate aceste tehnici pot fi utilizate
pentru a monitoriza schimbrile la nivelul grsimii intra-abdominale. Totui, ele sunt costisitoare i consum mult timp i trebuie mai degrab privite n practic
drept instrumente de cercetare specializate dect ca instrumente de rutin pentru evaluarea a riscului.
n prezent, nu par s existe dovezi puternice c msurarea taliei sau msurarea direct a masei de grsime
ar putea nlocui IMC n supravegherea de rutin a sntii publice sau n practica clinic.

Vol. 24, No. 4, 2014
4.6.4 Paradoxul obezitii n boala arterial

coronarian cunoscut
Dac la nivelul populaiei obezitatea se asociaz cu
un risc crescut de inciden a BCV i mortalitate datorat BCV, n rndul persoanelor cu boal arterial coronarian cunoscut dovezile sunt contradictorii. Analize sistematice ale pacienilor cu boal arterial coronarian sau supui PCI au sugerat existena unui paradox al obezitii, n care obezitatea pare s aib efect
protector mpotriva prognosticului nefavorabil366-369.
4.6.5 Tratament
Dei dieta, exerciiile i modificrile comportamentului sunt terapii principale pentru supraponderabilitate i obezitate (Tabelul 12), ele eueaz adesea n tratamentul pe termen lung. Terapia medical cu orlistat388
i/sau chirurgia bariatric389 pentru pacienii cu IMC
40 kg/m2 sau IMC 35 kg/m2 asociat cu comorbiditi cu risc crescut reprezint singurele opiuni. Aceti
pacieni ar trebui s fi ncercat nainte alte metode convenionale, de diet i exerciiu, ar trebui s nu sufere
de tulburri psihiatrice necontrolate i s fie suficient
de sntoi, astfel nct beneficiile interveniei s depeasc riscurile. Problemele majore n domeniul chirurgiei bariatrice sunt lipsa consensului n privina diverselor proceduri disponibile i a perfecionrii tehnicilor care vor avansa pentru a scdea riscurile asociate.

Tabelul 12. Clasificarea greutii corporale n funcie de indicele de

mas corporal la aduli387
Aduli (>18 ani)
Indice de mas corporal (kg/m2)
Subponderal
<18,5
Normal
18,5-24,9
Supraponderal
25-29,9
Obez
30
Clasa 1
30-34,9
Clasa 2
35-39,9
Clasa 3
40
Clasa 4
50
Clasa 5
60
Clasificrile Institutului Naional de Snatate (National Institute of Health) i a OMS nu conin clasele 4 i 5 de
obezitate.

Nu se poate exclude faptul c subponderabilitatea se asociaz cu morbiditate i mortalitate cardiovascular ridicat.
Lacune rmase
Dac msurtorile regionale ale adipozitii
adaug un beneficiu capacitii predictive a IMC
n identificarea persoanelor cu risc de boal cardiovascular.
Identificarea rolului relativ al dietei, exerciiilor i
modificrii conduitei n managementul persoanelor supraponderale i obeze.
Recomandri n ceea ce privete tensiunea arterial

Recomandri
Modificri ale stilului de via precum controlul greutii, creterea nivelului de activitate fizic, reducerea consumului de alcool, reducerea aportului de sare,
creterea aportului de fructe i legume i scderea aportului de grsimi saturate sunt recomandate tuturor pacienilor hipertensivi i celor cu tensiune normal
nalt.
Clasele principale de antihipertensive (de ex. diuretice, IEC, calciu-blocante, antagoniti ai receptorilor de angiotensin i beta-blocante) nu difer n mod
semnificativ n ceea ce privete eficacitatea lor n reducerea TA i pot fi recomandate pentru iniierea i meninerea tratamentului antihipertensiv.
Beta-blocantele i diureticele tiazidice nu sunt recomandate la pacienii hipertensivi cu factori de risc metabolici multipli, acestea crescnd riscul instalrii
diabetului zaharat.
La pacienii diabetici sunt indicai IECA sau blocani ai receptorilor de angiotensin.
Estimarea riscului folosind diagrama de risc SCORE este recomandat ca cerin minim la fiecare pacient hipertensiv.
Totui, existnd dovezi c afectarea subclinic de organ este un predictor independent al mortalitii de cauz
cardiovascular independent de SCORE, ar trebui ncurajat o cutare a afectrii subclinice de organ, n mod special la indivizii cu risc sczut sau moderat
(SCORE 1-4%).
Tratamentul medicamentos trebuie iniiat prompt la pacieni cu hipertensiune grad 3, precum i la pacieni cu hipertensiune grad 1 i 2 care prezint risc
cardiovascular total nalt i foarte nalt.
La pacieni cu hipertensiune grad 1 i 2, aflai la risc cardiovascular total moderat, tratamentul medicamentos poate fi amnat cteva sptmni, iar n cazul
celor cu hipertensiune grad 1 fr factori de risc asociai cteva luni, ncercndu-se normalizarea valorilor tensionale prin schimbarea stilului de via.
Tensiunea arterial sistolic ar trebui sczut <140 mmHg (iar cea diastolic <90 mmHg) la toi pacienii hipertensivi.
La toi pacienii hipertensivi cu boli cardiovasculare constituite sau cu diabet zaharat tip 2 sau cu risc al mortalitii de cauz cardiovascular estimat la 10 ani
5 %(conform diagramei SCORE) ar trebui sa fie luat n considerare tratamentul cu statine.
Tratamentul antiagregant plachetar, n special cu doze mici de aspirin, se recomand la pacienii hipertensivi cu evenimente cardiovasculare.
Tratamentul antiagregant plachetar poate fi luat n considerare i la pacienii hipertensivi fr istoric de boli cardiovasculare, dar cu funcie renal diminuat
sau cu risc cardiovascular nalt.
Clasaa
Nivelb
GRADE
Refc
Puternic
274,285,
390-393
Puternic
394
III
Puternic
395,396
I
I
A
B
Puternic
Puternic
397-399
45,400
IIa
Slab
45,400
Puternic
401
IIb
Slab
401
IIa
Puternic
402-404
IIa
Puternic
405
Puternic
398
IIb
Slab
406-408
Clasa de recomandri
Nivelul de eviden
c
Referine
a
b

4.7 Tensiunea arterial

Mesaj cheie
Hipertensiunea arterial reprezint un factor de
risc major pentru boala arteriala coronarian, insuficiena cardiac, patologia cerebrovascular,
arteriopatiile periferice, insuficiena renal i fibrilaia atrial.
4.7.1 Introducere
n numeroase studii epidemiologice, hipertensiunea arterial s-a dovedit a fi factor de risc pentru boala
arterial coronarian, insuficiena cardiac, bolile cerebro-vasculare, arteriopatiile periferice, insuficiena
renal, i mai recent i pentru fibrilaia atrial409,410. De
asemenea studii observaionale au artat c o cretere
a valorilor tensionale peste limitele fiziologice este invers corelat cu funcia cognitiv, hipertensiunea arterial asociindu-se astfel cu o inciden mai crescut a
demenei411. Date observaionale incluznd >1 milion
de subieci au evideniat c mortalitatea prin boli cardiace i accidente vasculare cerebrale crete progresiv
i linear cu creterea valorilor tensionale sistolice 115
mmHg i diastolice 75 mmHg412.
Creterea presiunii pulsului (tensiunea arterial sistolic minus tesiunea arterial distolic) s-a dovedit
n unele studii un predictor mai bun al evenimentelor
cardiovasculare, dect tensiunea arterial sistolic i
diastolic luate individual413, i totodat un parametru
important n identificarea pacienilor cu hipertensiune
arterial sistolic asociat cu un risc crescut414. Totui,
o metaanaliz incluznd 61 de studii (70% efectuate n
Europa)412, a artat o predictibilitate mai redus a presiunii pulsului fa de TAS i TAD, aceasta avnd ns un
rol mai important dup vrsta de 55 de ani.
Subiecii cu hipertensiune arterial cel mai adesea
prezint factori de risc cardiovascular asociai (diabet
zaharat, rezisten la insulin, dislipidemie)i leziuni de
organ-int. Deoarece factorii de risc au un efect cumulativ, riscul pacienilor hipertensivi se consider crescut
chiar i prin creterea uoar sau moderat a valorilor
tensionale.

Vol. 24, No. 4, 2014
4.7.2 Definiia i clasificarea hipertensiunii

arteriale
Tabelul 13. Definiia i clasificarea nivelurilor tensiunii arterialea
Categorie
Sistolic (mm/Hg)
Diastolic (mm/Hg)
Optim
<120
i
<80
Normal
120-129
i/sau
80-84
Normal nalt
130-139
i/sau
85-89
Hipertensiune grad 1
140-159
i/sau
90-99
160-179
i/sau
100-109
180
i/sau
110
Hipertensiune sistolic izolat
140
i
<90
a
valori ale tensiunii arteriale la pacienii netratai
Hipertensiunea sistolic izolat ar trebui clasificat

(1,2 i 3) n funcie de valorile tensionale sistolice corespunztoare gradelor, tensiunea arterial diastolic
fiind <90 mmHg. Gradele 1, 2 i 3 corespund hipertensiunii uoare, moderate i respectiv severe. Aceti termeni au fost n prezent omii cu scopul de a evita confuzia atunci cnd se ncearc clasificarea riscului cardiovascular total.
4.7.3 Evaluarea n scop diagnostic
Ghidurile n vigoare ale Societii Europene de Hipertensiune401 consider ca urmtoarele examinri paraclinice s fie efectuate ca teste de rutin la pacienii
hipertensivi: glicemia a jeun, colesterolul total, LDL
colesterol, HDL colesterol, trigliceridele a jeun, potasemia, uricemia, creatinina seric, clearance-ul estimat
al creatininei(conform formulei Cockcroft-Gault) sau
rata filtrrii glomerulare (utiliznd formula the Modification of Diet in Renal Disease (MDRD); ecuaia CKDEPI are o mai mare acuratee dect ecuaia MDRD n
special dac rata filtrrii glomerulare estimate >60 mL/
min/1,73 m2); hemoglobina i hematocritul, examenul
de urin(testul dipstick i microscopic pentru evaluarea microalbuminuriei; efectuarea proteinuriei cantitative n cazul pozitivrii dipstick-ului), ECG; n timp
ce urmtoarele teste sunt opionale: ecocardiografia,
ecografie carotidian, indicele glezn-bra, examenul
fundului de ochi i msurarea velocitii undei pulsului. Dac glicemia a jeun >5,6 mmol/L (100 mg/dL) sau
hemoglobina glicozilat (HbA1c) se afl ntre 5,7-6,4%
(Diabetes Control and Complications Trial - DCCTstandaridization) este recomandat a se efectua testul
toleranei la glucoz (vezi seciunea 4.8). Printre testele
recomandate se numr de asemenea msurarea tensiunii arteriale la domiciliu sau monitorizarea ambulatorie pe 24 h a tensiunii arteriale.

Vol. 24, No. 4, 2014
4.7.4 Msurarea tensiunii arteriale

Tensiunea arterial ar trebui msurat la fiecare individ de mai multe ori n zile diferite. Dac valorile
tesionale prezint doar o uoar cretere atunci se vor
efectua masurtori repetate pe parcursul a mai multor
luni, iar la final n funcie de rezultat se va lua n considerare iniierea sau nu a tratamentului antihipertensiv.
Dac valorile tensionale sunt mai important crescute
sau se asociaz cu leziuni subclinice de organ, ali factori de risc cardiovascular, boal cardiovascular constituit sau boal renal, monitorizarea valorilor tesnionale trebuie s se efectueze mai frecvent astfel nct s
se poat lua o decizie terapeutic optim. Msurtori
repetate ale TA sunt necesare pentru a exclude pacienii
care prezint doar o fals cretere a tensiunii arteriale, n general observat la primele vizite. S-ar putea ca
acest grup de populaie s necesite msurarea tensiunii arteriale mai frecvent dect populaia general, dar
probabil nu vor necesita tratament hipotensor, deoarece riscul lor cardiovascular este probabil mic.
La pacienii hipertensivi post-infarct miocardic este
posibil s se nregistreze valori tensionale mai sczute
dect anterior infarctului sau chiar s revin la valorile
normale fr tratament antihipertensiv. n aceste cazuri, ar trebui efectuate masurtori mai frecvente ale
TA pentru a nu fi omii pacienii la care tensiunea arterial revine la valorile anterioare infarctului i trebuie
renceput tratamentul antihipertensiv.
4.7.5 Msurarea tensiunii arteriale la cabinet sau
n clinic
Avnd n vedere c aparatele de msurare a tensiunii
arteriale pe baz de mercur au fost retrase de pe pia n
unele ri europene, aparatele de msurare fr mercur
au devenit tot mai rspndite.Aceste dispozitive trebuie testate n mod corespunzator si validate n conformitate cu protocoalele standardizate415. Dispozitivele
de msurare a TA la nivelul degetelor sau antebraului
ar trebui evitate datorit inexactitii metodei. Tehnica
ausculatoric cu un observator instruit i cu un sfigmomanometru cu mercur continu s fie metoda de elecie pentru monitorizare att n spital ct i la cabinet.
4.7.6 Monitorizarea ambulatorie i la domiciliu a
tensiunii arteriale
Att monitorizarea ambulatorie ct i cea la domiciliu a TA sunt strns legate de prognostic416. Monitorizarea poate fi util nu doar la pacienii netratai ci i
la pacienii aflai sub tratament, cu scopul de a monitoriza efectele tratamentului i de a crete compliana
la terapia medicamentoas. Permite, de asemenea diagnosticarea a dou condiii specifice i anume , hiper-

tensiunea de halat alb sau hipertensiunea izolat din

cabinetul medical, caracterizat prin valori crescute ale
TA la cabinet i valori normale ale TA n ambulator i
hipertensiunea mascat caracterizat prin valori normale ale TA la cabinet i valori crescute ale TA n ambulator.417 Valorile prag ale TA pentru definirea hipertensiunii arteriale la monitorizarea pe 24h a TA difer
de cele msurate la cabinet sau n spital (Tabelul 14).
Diagnosticul de hipertensiune i evaluarea tratamentului sunt nc n mare parte bazate pe valorile msurate la cabinet sau n spital.
Tabelul 14. Valorile prag ale tensiunii arteriale pentru definirea hipertensiunii cu diferite modaliti de msurare ale TA
TAS (mmHg) TAD (mmHg)
Cabinet sau spital
140
90
24 ore
125-130
80
Zi
130-135
85
Noapte
120
70
Acas
130-135
85
TA- tensiune arterial; TAS- tensiune arterial sistolic; TAD- tensiune arterial diastolic
4.7.7 Stratificarea riscului n hipertensiunea

arterial
Decizia de iniiere a tratamentului farmacologic depinde nu numai de valoarea TA, ci i de riscul cardiovascular total, fiind nevoie de efectuarea unei anamneze corespunztoare, examinare clinic i paraclinic
pentru a identifica:
prezena bolilor cardiovasculare constituite sau a
bolii renale
prezena BCV subclinice
co-existena altor factori de risc cardiovasculari.
Evidenierea bolilor cardiovasculare constituite sau a
bolii renale (Tabelul 15) cresc dramatic riscul de evenimente cardiovasculare ulterioare indiferent de nivelul
TA. Acest lucru se ntmpl i n cazul asocierii hipertensiunii cu ali factori de risc cardiovascular, nu n ultimul rnd cu diabetul zaharat.
Co-existena altor factori de risc (fumat, hipercolesterolemie, diabet zaharat, istoric familial de boli cardiovasculare precoce) sporete riscul asociat cu o cretere
uoar a TA45.
Stratificarea riscului utiliznd diagrama SCORE este
o cerin minim pentru fiecare pacient hipertensiv.
Avnd n vedere importana prezenei afectrii organelor int ca stadiu intermediar n evoluia bolilor
vasculare si ca un factor determinant al riscului cardiovascular global , ar trebui cutate cu atenie semnele de
interesare a organelor.

Hipertrofia ventricular stng (HVS) evideniat

electrocardiografic prin indicele Sokolow-Lyons, indicele Cornell, sau mai recent prin estimarea Novacode418, este un predictor independent a evenimentelor cardiovasculare. HVS pe ECG poate fi folosit ca
instrument de documentare a regresiei HVS, posibil
asociat cu reducerea incidenei fibrilaiei atriale nou
instalate419. Un studiu prospectiv recent s-a concentrat
pe voltajul undei R n aVL ca semn prognostic pentru
pacienii hipertensivi fr HVS evideniat pe ECG.
Ecocardiografia are sensibilitate crescut fa de
electrocardiografie n diagnosticarea HVS i estimarea
riscului cardiovascular i poate fi util n precizia stratificrii riscului global i ndrumarea terapiei. Anomaliile cardiace detectate prin ecocardiografie cuantific
mai exact masa ventriculului stng i patternul geometric al HVS i au o putere predictiv suplimentar420.
Ecografia carotidian cu msurarea IMT sau prezena plcilor prezic att infarctul miocardic ct i AVC421.
Ecografia limitat la arterele carotide comune (un loc
mai puin frecvent de ateroscleroz) mai probabil detecteaz doar hipertrofia vascular, n timp ce evaluarea aterosclerozei necesit, de asemenea, vizualizarea bifurcaiei i/sau a arterelor carotide interne unde
plcile sunt mult mai frecvente. Aceste modificri sunt
obinuite la pacienii hipertensivi netratai fr afectarea organelor int la examinarea de rutin; astfel, ecografia carotidian poate detecta de multe ori modificrile vasculare, fcnd astfel stratificarea riscului mult
mai precis.
Prezena afectrii arteriale poate fi de asemenea sugerat de un indice glezn-bra <0,9. Un IGB sczut
indic ateroscleroz avansat422, n timp ce msurarea
IMT carotidian este capabil s detecteze modificrile
precoce421.
Msurarea velocitii undei pulsului carotido-femural ofer o evaluare cuprinztoare non-invaziv a rigiditii arteriale423 i are o valoare predictiv independent pentru morbiditatea cardiovascular i cea general, evenimentele coronariene i AVC la pacienii
cu HTA esenial necomplicat precum i la populaia
general. Dei relaia dintre rigiditatea aortic i evenimente este continu, a fost sugerat un prag de peste
12 m/s ca o estimare potrivit a alterrii semnificative
a funciei aortice la pacienii hipertensivi de vrsta medie.
Diagnosticul de hipertensiune secundar de cauz
renal este bazat pe constatarea unei funcii renale reduse sau/i evidenierea albuminuriei. Insuficiena renal este clasificat n funcie de rata de filtrare glome

Vol. 24, No. 4, 2014
rular calculat folosind MDRD, formula Cockroft

Gault sau CKD-EPI. Cu ajutorul celor trei formule se
poate detecta afectarea uoar a funciei renale n special dac valoarea creatininei serice este nc n limite
normale i greutatea corporal este sczut i/sau vrsta este avansat.
La pacieni hipertensivi cu sau fr diabet, microalbuminuria, chiar sub valorile prag utilizate n prezent,
prevestete evenimentele cardiovasculare424 i o relaie
continu ntre mortalitatea de cauz cardiovascular
i de cauz non-cardiovascular i valorile raportului proteinurie/creatinin >3,9 mg/g la brbai i >7,5
mg/g la femei a fost raportat n mai multe studii. Microalbuminuria poate fi msurat din probele de urin
spontane (urina pe 24 h sau probele de urin din timpul nopii nu sunt indicate datorit inexactitii colectrii probelor) prin indexarea concentraiei albuminei
urinare la concentraia creatininei urinare.
n concluzie, exist dovezi c afectarea subclinic de
organ prezice mortalitatea cardiovascular independent de SCORE i combinaia poate mbunti estimarea riscului n special la subiecii aflai la risc sczut sau
moderat (SCORE 1-4 %)400.
4.7.8 Pe cine tratm i cnd iniiem tratamentul
antihipertensiv?
Decizia de iniiere a tratamentului antihipertensiv
depinde de TA (Tabelul 13) i de riscul cardiovascular
total (Tabelul 15). Toi pacienii a cror TA indic grad
2 sau 3 de hipertensiune la msuratori repetate sunt
candidai pentru tratament medicamentos; un numr
mare de trialuri placebo controlate au demonstrat c
la pacienii cu astfel de valori TA, scderea TA reduce
morbiditatea i mortalitatea cardiovascular independent de nivelul total de risc.
Dovezile pentru beneficiul tratrii pacienilor cu
HTA grad 1 sunt insuficiente, deoarece studiile anterioare la pacieni cu hipertensiune uoar au inclus n
cea mai mare parte pacieni aflai la risc inalt.
Promptitudinea n iniierea terapiei farmacologice
depinde de nivelul riscului cardiovascular total. O ntrziere n obinerea controlului TA la pacienii hipertensivi aflai la risc nalt este asociat cu un prognostic
nefavorabil. Tratamentul medicamentos ar trebui iniiat
ct mai repede n HTA gradul 3 precum i la pacienii
cu HTA gradul 1 i gradul 2 care au risc cardiovascular
total nalt sau foarte nalt. La pacienii cu HTA gr ad1
sau 2 cu risc cardiovascular moderat, terapia medicamentoas poate fi amnat pentru cteva sptmni, i
la cei cu HTA grad 1 fr ali factori de risc poate fi
amnat pentru cteva luni. Cu toate acestea, chiar i


Vol. 24, No. 4, 2014
la aceti pacieni, lipsa de control a TA dup o anumit

perioad de msuri ne-farmacologice, poate conduce la
adugarea unui medicament n tratament.
n general, tratamentul precoce de scdere a TA nainte de apariia leziunilor de organ sau nainte ca acestea s devin ireversibile, este o recomandare prudent.
Acest lucru se datoreaz faptului c, la pacienii hipertensivi cu risc ridicat, chiar i terapia cardiovascular
intens, dei benefic, nu poate scdea riscul cardiovascular total sub pragul de risc nalt.
Iniierea terapiei medicamentoase la pacienii diabetici cu TA normal nalt nu este n prezent susinut
de dovezile din studii. Pentru moment, este prudent s
se recomande iniierea terapiei la pacienii diabetici cu
TA normal nalt, dac sunt prezente leziuni subclinice
de organ (n special microalbuminuria i proteinuria).
La subiecii cu TA normal nalt (TAS 130-139
mmHg, TAD 85-89 mmHg) necomplicat de diabet
sau evenimente cardiovasculare anterioare, nu exist
nicio dovad a beneficiului tratamentului, exceptnd o
ntrziere a debutului hipertensiunii.
Modificarea stilului de via i atenta monitorizare a
TA sunt recomandate indivizilor cu TA normal nalt
care au risc adiional sczut sau moderat401.
4.7.9 Cum tratm

4.7.9.1 Stilul de via
Msurile de modificare ale stilului de via singure,
pot fi suficiente la pacienii cu TA uor crescut i ar
trebui recomandate ntotdeauna i pacienilor cu medicaie antihipertensiv, putnd determina scderea
dozei de medicament necesar obinerii unui control
al TA.
Modificarea stilului de via include: scderea greutii corporale la pacienii supraponderali, reducerea
consumului de sare la <5 g/zi, restricia consumului de
alcool la nu mai mult de 20 g/zi de etanol la brbai i
10 g/zi de etanol la femei, i activitatea fizic regulat la
persoanele sedentare.
Efectul de scdere a TA n cazul creterii valorilor
potasiului a fost bine documentat n cazul dietei DASH
(bogat n fructe, legume i produse lactate degresate
cu un coninut redus de colesterol i grsimi saturate).
Astfel pacienii hipertensivi ar trebui sftuii s consume mai multe fructe i legume (4-6 porii pe zi, de
exemplu 400 g) i s reduc aportul de grsimi saturate
i colesterol.
Deoarece fumatul are o influen particular asupra
riscului cardiovascular, ar trebui depuse eforturi pentru a ajuta pacienii hipertensivi fumtori s renune la
Tabelul 15. Factori care influeneaz prognosticul n hipertensiune

Factor de risc
Afectare de organ int
TAS i TAD
HVS pe ECG ( Sokolow-Lyons >38 mm sau Cornell
>2440 mm/ms) sau Novacode LVMI>130 g/m2(F),
>115 g/m2(B).
Presiunea pulsului (la pacienii vrstnici)
Vrsta (B >55 ani, F >65 ani)
Fumatul
Dislipidemie: Col Total >5,0 mmol/l (190 mg/dl); sau
LDL col >3,0 mmol/l (115 mg/dl); sau HDL col <1,0
mmol/l (40 mg/dl) (B) , <1,2 mmol/l (46 mg/dl) (F); sau
Trigliceride >1,7 mmol/l (150 mg/dl)
Glicemia a jeune 5,5-6,9 mmol/L (100-125 mg/dl)
Test de toleran la glucoz modificat

Obezitate abdominal: circumferina taliei >102 cm (B),
>88 cm (F)
HVS detectat ecocardiografic ( LVMI 125 g/m2

(B), 110 g/m2 (F)
ngroarea peretelui carotidian (IMT >0,9 mm)
sau plci
Velocitatea undei pulsului carotido-femural >12
m/s
Indice glezn-bra <0,9
Diabet zaharat
BCV constituit sau boal renal
Glicemie a jeune 7,0 mmol/L (126 Boli cerebrovasculare: AVC ischemic, hemoragie
mg/dl) sau glicemie postprandial
cerebral, atac ischemic tranzitor
>11,0 mmol/L ( 198 mg/dl)
Boli cardiace: infarct miocardic, angin, revascularizare coronarian, insuficiena cardiac.
Boli renale: nefropatie diabetic, insuficien renal
(creatinina seric >133 umol/L (1,5 mg/dl)(B), >124
umol/l (1,4 mg/dl) (F), proteinurie (>300 mg/24 h).
Boal arterial periferic
Retinopatie avansat: hemoragie sau exudate, edem
papilar.
Uoar cretere a creatininei serice : 115-133

umol/l (1,3-1,5 mg/dl) (B), 107-124 umol/l (1,2-1,4
mg/dl) (F)
RFG sczutb (<60 ml/min/1,73 m2) sau clearance
la creatininc (<60 ml/min)
Microalbuminurie 30-300 mg/24 h sau raportul
albumin/creatinin: 22 mg/g (2,5 mg/mmol)
(B), 31 mg/g (3,5 mg/mmol) (F)
Istoric familial de BCV precoce: vrsta <55ani (B), <65

(F).
IGB - indice glezn-brat; BCV - boli cardiovasculare; TAD - tensiune arterial diastolic; RFG-rata de filtrare glomerular; F- femei; IMT- indice intim-medie; LDL- low density lipoprotein; HVS- hipertrofie ventricular stnga; LVMI- index de
mas ventricular stng, B-brbai; TAS - tensiune arterial sistolic; Col total- colesterol total; TG - trigliceride.
a
Risc maxim pentru HVS concentric: LVMI crescut cu un raport grosime perete/raz 0,42.
b
formula Modification of Diet in Renal Disease (MDRD)
c
formula Cockcroft Gault.

fumat putnd fi luate n considerare terapia de substituie nicotinic, terapia cu bupropione sau varenciclin.
Deoarece fumatul poate s creasc valorile tensionale
diurne, renunarea la fumat ar putea conduce la un mai
bun control al valorilor tensionale 425 cel puin la marii fumtori. ntruct compliana pe termen lung a modificrii stilului de via poate fi deficitar, este necesar
ntrirea recomandrilor o dat cu msurarea TA.
4.7.9.2 Medicaia antihipertensiv
Numrul mare de studii randomizate efectuate asupra medicaiei antihipertensive, att studiile care compar medicamentele active cu medicaia placebo, ct
i cele care compar scheme de tratament bazate pe
diferii compui, confirm urmtoarele: i) principalele
beneficii ale tratamentelor antihipertensive se datoreaz scderii TA per se, fiind n mare msur independente de medicamentele utilizate; ii)diureticele tiazidice i tiazidic-like (clortalidona i indapamida), beta
blocantele, antagonitii canalelor de calciu, inhibitorii
enzimei de conversie i antagonitii receptorilor de angiotensin pot s reduc ntr-un mod adecvat TA, i s
scad semnificativ riscul de mortalitate i morbiditate
cardio-vascular. Astfel, toate aceste medicamente sunt
recomandate pentru iniierea i ntreinerea unui tratament antihipertensiv fie ca monoterapie sau n diferite
combinaii.
Poziia beta blocantelor ca prim alegere n medicaia antihipertensiv a fost pus la ndoial n ultimul
deceniu. Cea mai recent meta-analiz a 147 de studii
randomizate 394 raporteaz doar o uoar inferioritate
a beta blocantelor n prevenirea accidentului vascular
cerebral (17% comparativ cu 29% n cazul altor ageni),
dar un efect similar cu alte medicamente n prevenirea
evenimentelor coronariene i a insuficienei cardiace
i o eficacitate mai mare dect alte substane la pacienii cu un eveniment coronarian recent. Aceste constatri sunt n concordan cu studiul United Kingdom
Prospective Diabetes Study (UKPDS)426. De asemenea,
aceste rezultate coincid cu un studiu observaional
complex efectuat pe subieci cu diferite regimuri de
medicaie antihipertensiv, pentru o perioad mai lung de timp dect n studiile clinice randomizate, i n
care incidena evenimentelor coronariene nu a fost mai
mare n cazul tratamentului bazat pe atenolol comparativ cu alte hipotensoare405.
Cu toate acestea, deoarece beta blocantele induc cretera n greutate, au efecte adverse asupra metabolismului lipidic395 i cresc (comparativ cu alte medicamente)
incidena de diabet zaharat, nu sunt de preferat la pacienii hipertensivi cu multipli factori de risc metabolici

Vol. 24, No. 4, 2014
(de exemplu: obezitatea abdominal, alterarea glicemiei jeun i scderea toleranei la glucoz), condiii care
cresc riscul de debut al diabetului zaharat. Acest lucru
este valabil i pentru diureticele tiazidice, care au efecte
dislipidemice i diabetogene, n mod special cnd sunt
utilizate n doze mari. In studiile care au artat un exces
relativ al diabetului zaharat, diureticele tiazidice au fost
frecvent administrate mpreun cu beta blocantele, facnd astfel dificil de apreciat distincia ntre contribuia
fiecrui agent medicamentos la acest proces. Cu toate
acestea, acest lucru se poate s nu fie valabil pentru beta
blocantele vasodilatatoare precum carvedilol i nebivolol, care au aciune dismetabolic uoar sau chiar
absent, i o inciden mai redus a diabetului zaharat
comparativ cu beta blocantele convenionale. De asemenea este nc neclar dac diabetul zaharat indus de
medicamente are acelai pronostic negativ cu cel aprut
n condiii naturale.
Studiile care au evaluat endpointuri moderate sugereaz alte diferene ntre diferite medicamente antihipertensive sau compui: inhibitorii enzimei de conversie i antagonitii receptorilor de angiotensin sunt n
mod particular eficieni n reducerea hipertrofiei ventriculului stng, inclusiv a componentei fibroase; sunt
de asemenea destul de eficieni n reducerea microalbuminuriei i proteinuriei, n pstratea funciei renale
i n ntrzierea apariiei stadiului final de boal renal;
Blocantele canalelor de calciu, n afar de faptul c sunt
eficiente n hipertrofia ventriculului stng, aparent sunt
eficiente n ncetinirea progresiei hipertrofiei carotidiene i a aterosclerozei.
Dovezile cu privire la beneficiile altor clase de medicamente sunt mult mai limitate. Alfa1-blocantele,
agenii cu aciune central [agonitii adrenoreceptorilor alfa2, agonitii receptorilor de imidazol (I1)], medicamentele antialdosteronice scad eficient TA. Totui,
nu sunt date care s documenteze abilitatea acestora de
a reduce morbiditatea i mortalitatea cardio-vascular. Cu toate acestea, toi aceti ageni au fost utilizai
n mod frecvent ca medicaie asociat n diferite studii
de documentare a proteciei cardiovasculare, i pot fi
astfel folosii n tratamentul combinat al TA.
Aliskirenul, care inhib efectul reninei i al pro-reninei pe receptorii specifici, scade eficient tensiunea427
i are efect antiproteinuric. Cu toate acestea, efectul su
asupra mortalitii i morbiditii cardio-vascualre nu a
fost nc dovedit, dar un numr de studii se afl n curs
de desfurare.
Considerentele legate de costuri nu ar trebui s predomine asupra eficacitii, tolerabilitii i siguranei

Vol. 24, No. 4, 2014
fiecrui pacient n parte. Medicamentele cu aciune pe

24 de ore ar trebui preferate. Simplificarea tratamentului mbuntete aderena pacientului, n timp ce
controlul eficient al TA pe 24 de ore este important din
punct de vedere al prognosticului n plus fa de controlul TA la cabinet. Medicamentele cu aciune prelungit minimalizeaz variabilitatea valorilor TA, ceea ce
poate oferi protecie mpotriva progresiei leziunilor de
organ i mpotriva riscului evenimentelor cardio-vasculare.
4.7.9.3 Tratamentul combinat
Tratamentul combinat este necesar pentru a controla
TA la majoritatea pacienilor. Adugarea unui medicament dintr-o alt clas trebuie considerat ca o strategie de tratament recomandabil, dac medicamentul
iniial trebuie retras din cauza efectelor secundare, sau
datorit ineficacitii. Reducerea TA determinat de
asocierea a dou substane din clase diferite, este de 5
ori mai puternic dect dublarea dozei unui singur medicament428. Combinaia a dou medicamente ar putea
s ofere avantaje i la iniierea tratamentului, n mod
particular la pacienii cu un risc crescut, la care controlul precoce al TA este de dorit. Asociaiile medicamentoase cu doze fixe simplific tratamentul i mbuntesc compliana pacientului. Dovezi ale eficienei
scderii TA, au fost obinute n mod particular pentru
combinaia dintre un diuretic i inhibitor de enzim de
conversie sau antagonist al receptorilor de angiotensin
sau blocant de canale de calciu429,430.
n ciuda dovezilor din studii de scdere a evenimentelor, combinaia de diuretic i beta blocant favorizeaz
apariia diabetului i ar trebui evitat, cu exceptia situaiilor n care sunt necesare din alte motive. Combinarea
unui inhibitor de enzim de conversie cu un antagonist
de receptor de angiotensin este asociat cu o cretere
semnificativ a efectelor secundare grave431. Beneficiile
la pacienii diabetici cu proteinurie (datorit efectului
antiproteinuric superior) ateapt confirmarea trialurilor.
La 15-20% din pacienii hipertensivi, este necesar
o combinaie de trei medicamente pentru a se obine
controlul TA; cea mai raional combinaie pare s fie:
un blocant al sistemului renin-angiotensin-aldosteron, un blocant de canale de calciu i un diuretic n
doze eficiente.
4.7.9.4 intele TA
Exist suficiente dovezi pentru a recomanda ca TAS
s fie redus la <140 mmHg (i TAD la <90 mmHg) la

toi pacienii hipertensivi. Dovezile lipsesc doar n cazul pacienilor vrstnici, n cazul crora beneficiile scderii TAS la <140 mmHg nu au fost testate n trialurile
randomizate.
Recomandarea ghidurilor anterioare401 de a inti o
TAS mai sczut (<130 mmHg) la pacienii diabetici
i la cei cu risc cardiovascular foarte nalt (cu evenimete cardiace anterioare) nu este susinut de dovezile
din studii. Analiza trialurilor efectuate pe scar larg
(ex. ONTARGET, INVEST i VALUE), dei afectat
de comparaia cu studiile non-randomizate, sugereaz c cel puin la pacienii hipertensivi cu risc cardiovascular nalt, scderea TAS sub 130 mmHg nu aduce
beneficii, sau poate chiar s duneze, exceptnd poate
accidentul vascular cerebral. Un fenomen de tip curb
J, nu poate fi exclus pentru atingerea valorilor TAS sub
130 mmHg432.
n ciuda limitrilor lor evidente i a puterii sczute a
dovezilor, analizele post-hoc indic o reducere progresiv a incidenei evenimentelor cardiovasculare concomitent cu scderea progresiv a TAS la ~120 mmHg
i TAD la ~75 mmHg421, dei beneficiul suplimentar la
valori sczute ale TA devine mic. Un fenomen de tip
curb J este puin probabil s apar mai jos fa de aceste valori, cu excepia probabil a pacienilor cu boal
aterosclerotic avansat.
Pe baza datelor actuale, ar putea fi prudent s se recomande scderea TAS/ TAD la valori cuprinse n intervalul 130-139/80-85 mmHg, i eventual apropiat de
valorile minime ale acestui interval, la toi pacienii hipertensivi. n acest sens sunt necesare mai multe dovezi
de la trialurile controlate randomizate.
4.7.9.5 Hipertensiunea n condiii speciale
Diabetul zaharat (vezi Seciunea 4.8.)
La pacienii diabetici, tratamentul antihipertensiv ar
trebui iniiat ntotdeauna cnd TA este 140/90 mmHg.
In prezent iniierea tratamentului n cazul TA normal
nalte, nu este susinut de dovezile din studiile clinice.
Meta-analiza trialurilor disponibile, arat c n diabet, toate clasele majore de antihipertensive protejeaz
mpotriva complicaiilor cardiovasculare, probabil prin
efectul protector de scdere a TA per se. De aceea pot
fi luate toate n considerare n momentul alegerii tratamentului. Asociaiile medicamentoase sunt de obicei
necesare pentru reducerea TA n diabet. Un blocant al
sistemului renin-angiotensin-aldosteron (inhibitor
de enzim de conversie/ antagonist de receptor de angiotensin) ar trebui ntotdeauna introdus din cauza
efectelor superioare de protecie mpotriva iniierii i
progresiei nefropatiei.

Hipertensiunea arterial la vrstnici

Meta-analizele extinse confirm faptul c tratamentul n cazul vrstnicilor hipertensivi este extrem de benefic. Beneficiul pacienilor n vrst de >65 de ani nu
este mai mic dect al pacienilor tineri.
Afirmaia conform creia, diferite clase de antihipertensive difer semnificativ n abilitatea lor de a scdea
TA i de a reduce riscul cardiovascular la vrstnici comparativ cu tinerii, nu a fost demonstrat. Astfel, alegerea
medicamentului nu ar trebui ghidat de vrst. Diureticele tiazidice, inhibitorii enzimei de conversie, blocantele canalelor de calciu, antagonitii receptorilor de
angiotensin i beta blocantele pot fi utilizate pemtru
iniierea i ntreinerea tratamentului i la vrstnici.
n cazul vrstnicilor, studiile realizate s-au adresat
doar pacienilor cu o TAS 160 mmHg, i n nici un
studiu nu s-a atins o TAS medie de <140 mmHg. Este
necesar efectuarea unor studii la pacieni cu valori
tensionale de iniiere mai sczute i atingerea unor valori mai sczute ale TA sub tratament.
Dovezi conform crora tratamentul antihipertensiv
are beneficii i la pacienii cu vrsta 80 ani sunt acum
disponibile n urma unui studiu efectuat. Tratamentul
hipotensor ar trebui iniiat sau continuat cnd pacientul mplinete vrsta de 80 de ani, ncepnd cu monoterapie i adugnd un al doilea medicament dac
e necesar. Deoarece pacienii hipertensivi din studiul
Very Elderly Trial (HYVET) au fost n general ntr-o
stare bun433, ncercarea de a extrapola datele HYVET
la pacienii octogenari, care sunt mult mai fragili, este
incert. Decizia de a trata ar trebui luat n funcie de
individ, i pacienii ar trebui s i monitorizeze cu
atenie TA pe durata tratamentului, inclusiv msurarea
TA n ortostatism.
4.7.9.6 Durata tratamentului
n general, tratamentul antihipertensiv trebuie meninut pe termen nelimitat. ntreruperea tratamentului
la pacienii hipertensivi este urmat n mare parte de
revenirea TA la valorile anterioare tratamentului.
4.7.9.7 Medicamente hipolipemiante
Toi pacienii hipertensivi cu boli cardiovasculare
diagnosticate sau cu diabet zaharat de tip 2 sau cu un
risc cardiovscular estimat la 10 ani 5% (pe baza diagramei SCORE) trebuie luai n considerate pentru terapia cu statine ce vizeaz atingerea obiectivelor int
menionate la seciunea 4.9.
4.7.9.8 Tratamentul cu antiagregante plachetare
Tratamentul antiplachetar, n special aspirina n doze
mici, ar trebui s fie prescris la pacienii hipertensivi

Vol. 24, No. 4, 2014
cu evenimente cardiovasculare. Poate de asemenea, s

fie luat n considerare la pacienii hipertensivi fr istoric de boli cardiovasculare, cu funcie renal redus,
sau la cei cu risc cardiovascular ridicat. Pacienilor crora li se administreaz aspirin ar trebui s le fie acordat ntotdeauna o atenie crescut datorit riscului de
sngerare, n special gastro-intestinal.
Informaii noi importante
Leziunile subclinice de organ n hipertensiune
sunt un factor predictiv al decesului cardiovascular independent de riscul SCORE, iar asocierea
celor dou poate mbunti predicia riscului de
deces, n special la persoanele cu risc cardiovascular mic i moderat (SCORE 1-4%).
Tratamentul antihipertensiv este benefic la pacienii cu vrsta 80 ani.
Lacunele rmase
Ar trebuie prescrise medicamente antihipertensive tuturor persoanelor cu hipertensiune arterial gradul 1, chiar i atunci cnd riscul de cardiovascular total este sczut sau moderat?
Ar trebui prescris medicaie antihipertensiv
vrstiniclor cu hipertensiune arterial gradul 1,
i ar trebui s fie stabilit i n cazul lor valoarea
int a TA <140/90 mmHg?
Ar trebui iniiat tratamentul medicamentos la
pacienii cu diabet zaharat sau la cei cu un eveniment vascular cerebral sau boli cardiovasculare
atunci cnd TA este nc n intervalul normal/
crescut, i ar trebui ca inta TA s fie <130/80
mmHg la aceti pacieni?
Care sunt cele mai mici valori TA sigure de atins
prin tratament n diferite condiii clinice?
Poate stilul de via echilibrat, despre care se tie
c reduce TA, s fie de asemenea responsabil de
reducereea morbiditii i mortalitii n hipertensiune?
4.8 intele terapeutice la pacienii cu diabet
zaharat de tip 2
Mesaje cheie
Managementul intensiv al hiperglicemiei n diabetul zaharat reduce riscul de complicaii microvasculare i, ntr-o mai mic msur, cel al
bolilor cardiovasculare.
Tratament intensiv al TA n diabetul zaharat reduce riscul complicaiilor macrovasculare i microvasculare.

Vol. 24, No. 4, 2014
Asocierile medicamentoase antihipertensive

sunt de obicei necesare pentru a atinge valorile
int.
4.8.1 Introducere
Boala cardiovascular este principala cauz de morbiditate i mortalitate la persoanele cu diabet zaharat.
Controlul agresiv al hipertensiunii arteriale i scderea
nivelului de colesterol cu statine reduce riscul de evenimente cardiovasculare, i exist dovezi concludente c
mbuntirea controlului glicemic reduce semnificativ
riscul de a dezvolta complicaii diabetice microvasculare (retinopatie, nefropatie, i neuropatie). n timp ce
datele existente indic o relaie ntre nivelurile crescute ale glicemiei i evenimentele cardiovasculare, pn
de curnd au existat puine dovezi care s specifice c
atingnd valorile int ale glicemiei se poate reduce
frecvena evenimentelor cardiovasculare.
4.8.2 Dovezi ale recomandrilor actuale privind
prevenirea bolilor cardiovasculare n diabet
Cu excepia gestionrii nivelului glucozei, preveniia
BCV urmeaz aceleai principii generale ca i pentru
persoanele care nu au diabet zaharat. O abordare multifactorial n ceea ce privete tratamentul i atingerea
unor valori sczute ale TA i ale concentraiilor de LDL
colesterol i colesterol total este deosebit de important, i multe dintre intele tratamentului sunt mai dificil
de obinut la pacienii cu diabet zaharat. Pacientul tipic
cu diabet zaharat de tip 2 prezint multipli factori de
risc cardiovasculari, fiecare dintre acetia trebuind s
fie tratat n conformitate cu ghidurile existente.
4.8.3 Controlul glicemiei
Studiul UKPDS a evaluat efectul imbuntirii controlului metabolic asupra riscului de a dezvolta eveni-

mente coronariene sau alte evenimente cardiovasculare434,439. Studiul a demonstrat o reducere cu 16% a
riscului pentru infarct miocardic, care nu a fost semnificativ statistic (p=0,052) n cazul unei diferene de
0,9% a HbA1c ntre grupul cu tratament agresiv i cel cu
terapie convenional. Media valorilor HbA1c n grupul
cu tratament intensiv a fost de 7,0% (53 mmol/mol).
La pacienii supraponderali tratai cu metformin, a fost
observat o reducere semnificativ a riscului de infarct
miocardic (p <0,01).
Majoritatea pacienilor din UKPDS au fost urmrii
pe o perioad de nc 10 ani post-studiu pentru monitorizare444. Nu a fost fcut nici o ncercare n vederea
meninerii terapiei atribuite anterior i controlul glicemic n cele dou grupuri a devenit rapid convergent.
Grupul cu tratament intensiv a avut o reducere de
17% a riscului relativ de decese cauzate de diabet (p =
0,01), o reducere de 15% a riscului de infarct miocardic (p = 0,01), i o reducere de 13% a riscului de deces
de orice alt cauz (p = 0,007). Acest aa-numit efect
de motenire, de asemenea, s-a observat i n grupul
celor tratai cu metformin, n care pacienii tratai cu
metformin au meninut un nivel redus al evenimentelor cardiovasculare, comparativ cu cei care erau pe
terapia convenional. Efectul similar de motenire
a fost observat la pacienii cu diabet zaharat de tip 1
cu control glicemic precoce intensiv n studiul DCCT
/EDIC445.
4.8.4 Valorile int ale glicemiei
Au fost efectuate trei studii recente pentru a vedea
dac evenimentele cardiovasculare ar putea fi reduse
i mai mult dac s-ar reduce valoarea int a HbA1c435,
438,446
. n cadrul studiului ACCORD >10 000 de pacieni
cu diabet zaharat de tip 2 i fie cu istoric de BCV, fie
Recomandri cu privire la diabetul zaharat

Recomandri
Pentru prevenirea BCV la diabetici se recomand ca valoare int a HbA1c s fie <7,0% (<53 mmol/mol).
Statinele sunt recomandate pentru a reduce riscul cardiovascular n diabetul zaharat.
Hipoglicemia i luarea excesiv n greutate trebuie evitate i la pacienii cu boli complexe pot fi necesare abordri individuale (att n ceea ce
privete valorile int ct si opiunea medicamentoas).
Metforminul ar trebui utilizat ca terapie de prim linie, dac este tolerat i nu are contraindicaii.
Reducerea suplimentar a HbA1c la o valoare int de <6,5% (<48 mmol/mol) (cel mai sczut nivel posibil al HbA1c care poate fi atins n siguran)
ar putea fi util pentru boala nou diagnosticat. Pentru pacienii cunoscui de mult timp cu diabet zaharat acest int poate reduce riscul complicaililor microvasculare.
Valorile int ale TA n diabet se recomand sa fie <140/80 mmHg.
inta LDL colesterol este <2,5 mmol/L, pentru pacienii fr patologie aterosclerotic valoarea colesterolului total poate fi <4,5 mmol/l, cu o int
mai mic a LDL colesterol de <1,8 mmol/L (utiliznd doze mai mari de statine) pentru pacienii diabetici cu risc foarte mare de BCV.
Terapia antiagregant plachetar cu aspirin nu este recomandat la pacienii cu diabet zaharat care nu au dovezi clinice ale bolii aterosclerotice.
Clasaa
I
I
Nivelb
A
A
GRADE
Puternic
Puternic
Puternic
IIa
Puternic
Refc
434, 435
166, 436
435, 437,
438
439
IIb
Slab
435
Puternic
440, 441
IIb
Slab
442
III
Puternic
443
SCA = sindrom coronarian acut; TA = tensiune arterial; BCR = boa cronic de rinichi; BCV = boli cardiovasculare; HbA1c = hemoglobina glicozilat; LDL = lipoproteine cu densitate sczut
a
Clasa de recomandare.
b
Nivel de eviden.
c
Referine.

cu factori de risc cardiovascular adiionali au fost

randomizai la o terapie agresiv, cu o int a HbA1c
<6,0% (42 mmol/mol) sau la control glicemic standard (inta HbA1c 7,0-7,9%, 53-63 mmol/mol). HbA1c
a sczut rapid n grupul cu terapie agresiv, cu o medie a HbA1c de 6,7% (50 mmol/mol) n 4 luni i 6,4%
(46 mmol/mol) la 1 an. Studiul a fost oprit prematur
la 3,5 ani din cauza unei creteri semnificative a ratei
mortalitii totale n grupul cu tratament agresiv: 257
vs 203 (p = 0,04) pentru decesele din orice cauz i 135
vs 94 (p = 0,02) pentru decese din cauze cardiovasculare. Au fost semnificativ mai multe cazuri de hipoglicemie care au necesitat intervenie terapeutic n cadrul
grupului cu terapie agresiv, i care au prezentat, de
asemenea, o cretere semnificativ n greutate. Motivul
pentru prognosticul mai slab n grupul cu terapie agresiv nu este clar, dar ar putea fi asociat cu hipoglicemia.
Studiul ADVANCE (Action in Diabetes and Vascular Disease) a randomizat >11 000 de pacieni cu diabet zaharat de tip 2 ntr-un grup cu control standard
al glicemiei i unul cu control intensiv435. Valoarea
int a HbA1c a fost de 6,5% (48 mmol/mol) (cu 0,5%
mai mare dect n ACCORD). Valoarea medie final
a HbA1c a fost similar cu cele din studiul ACCORD,
dar reducerea HbA1c n grupul cu terapie agresiv a fost
atins mai trziu n ADVANCE, cu o medie la 6 luni
a HbA1c de 7% (53 mmol/mol) i care nu ating valoarea final de 6,5% (48 mmol/mol) pn la ~36 de luni.
Control intensiv a redus n mod semnificativ numrul
total de evenimente majore macrovasculare (moartea
de cauze cardiovasculare, infarct miocardic non-fatal,
accident vascular cerebral non-fatal) i evenimente majore microvasculare (nefropatia sau retinopatia nou
sau agravat), dar numai reducerea evenimentelor microvasculare a fost semnificativ statistic. Creterea n
greutate i hipoglicemia au fost mai puin frecvente dect n studiul ACCORD.
Studiul mai mic VADT (Veterans Affairs Diabetes
Trial) a atins o medie a HbA1c de 6,9% (52 mmol/mol)
n grupul cu terapie agresiv comparativ cu 8,4% (68
mmol/mol) n grupul standard438. Nu a fost nici o diferen semnificativ ntre grupuri n ceea ce privete
obiectivele primare i nici pentru mortalitatea de orice
cauz.
4.8.5 Meta-analize i recenzii sistematice
O meta-analiz asupra controlului intensiv al glicemiei ce a inclus date din UKPDS, PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events),
ACCORD, ADVANCE, i VADT447 a artat o reducere semnificativ a infarctului miocardic non-fatal i a

Vol. 24, No. 4, 2014
evenimentelor coronariene, dar nici un efect asupra

accidentului vascular cerebral sau a mortalitii totale. Aceast analiz poate fi contestat ntruct studiul
PROactive a fost un studiu cu pioglitazon comparativ
cu placebo, i nu un studiu al controlului intens al valorilor glicemice448. O meta-analiz mai recent a examinat studiile cu control glicemic intensiv comparativ cu
cel convenional, dar nu a inclus studiul PROactive, i a
utilizat din nou studiile UKPDS, ACCORD, ADVANCE, i VADT449. Rezultate similare au fost observate n
ceea ce privete reducerea semnificativ a evenimentelor coronariene i a BCV, dar nu s-a evideniat nici o reducere a mortalitii cardiovasculare sau a mortalitii
totale. Un rezultat similar a fost, de asemenea, gsit la o
alt examinare sistematic ale acelorai date450.
4.8.6 Tensiunea arterial
Hipertensiunea arterial este mai frecvent ntlnit
la pacienii cu diabet zaharat de tip 2 comparativ cu
populaia general. Efectul reducerii TA asupra riscului
de apariie a BCV a fost urmrit n studii clinice, care
au inclus att pacieni diabetici ct i pacieni non-diabetici, iar o mare parte din dovezile existente se bazeaz
pe analiza de subgrup ale acestor studii combinate. De
exemplu, n studiile SHEP (Systolic Hypertension in the
Elderly Program) i Syst-Eur (Systolic Hypertension in
Europe), efectele tratamentului au fost, n general, mai
pronunate n grupurile cu diabet zaharat dect n grupurile fr diabet. Studiul HOT (Hypertension Optimal
Study), care a comparat diferite valori int ale TAD,
a demonstrat beneficiile unui tratament mai agresiv al
TA (valoarea int a TAD: 80 mmHg), care a constat
ntr-o reducere a riscului de evenimente la indivizii diabetici comparativ cu nondiabetici440.
ntr-un substudiu al UKPDS, pacienii cu hipertensiune arterial au fost randomizai n funcie de terapia agresiv (TA medie 144/82 mmHg) sau mai puin
agresiv441. A existat o reducere marcat i semnificativ a riscului de accident vascular cerebral cu 44% i
o reducere nesemnificativ cu 21% a riscului pentru
infarct miocardic, n cazul unei reduceri de 10 mmHg
a TAS i de 5 mmHg a TAD. Monitorizarea dup terminarea substudiului UKPDS nu a artat nici un efect
motenire (de exemplu, controlul intensiv al TA trebuie meninut pentru continuarea beneficiului)426. n
studiul ADVANCE, reducerea TA la o medie de 135/75
mmHg scade suplimentar riscul evenimentelor cardiovasculare i al mortalitii totale397.
La pacienii diabetici, tratamentul antihipertensiv ar
trebui s fie iniiat atunci cnd TA este 140/80 mmHg.
Valoarea int clasic a TAS recomandat n diabet za-

Vol. 24, No. 4, 2014
harat (130 mmHg), se bazeaz pe dovezi epidemiologice, i nu pe dovezi ale studiilor randomizate. Acest
valoare a fost, de asemenea, foarte dificil de obinut la
majoritatea pacienilor. Recentul studiu ACCORD TA
451 a testat ipoteza dac o valoare int a TAS <120
mmHg ar aduce un beneficiu suplimentar n reducerea
evenimentelor cardiovasculare la pacienii cu diabet
zaharat de tip 2. Nu s-a observat nici o mbuntire n
ceea ce provete obiectivele primare, cu mici reduceri
n ceea ce privete obiectivele secundare de accidente
vasculare cerebrale, i s-a observat o uoar cretere a
efectelor adverse cu reducerea valorilor int.
Meta-analizele studiilor disponibile arat c, n diabetul zaharat, toate marile clase de medicamente antihipertensive protejaz mpotriva complicaiilor cardiovasculare, probabil din cauza efectului protector al
scderii TA per se. Astfel, toate aceste medicamente pot
fi luate n considerare n aceast populaie.
Tratamentul combinat este de obicei necesar n reducerea eficient a TA n diabetul zaharat. Un inhibitor
al ECA sau antagonist al receptorilor de angiotensin
ar trebui s fie ntotdeauna luat n considerare datorit
efectului protector superior dovedit mpotriva iniierii
sau progresiei nefropatiei.
4.8.7 Dislipidemia
Studiul Heart Protection (HPS) a demonstrat c
tratamentul cu simvastatin 40 mg reduce riscul cardiovascular i cel de evenimente vasculare cerebrale la
pacienii diabetici i nondiabetici fr antecedente de
infarct miocardic sau de angin pectoral436. Efectul
tratamentului a fost independent de nivelul de baz
al colesterolului dei riscul absolut i eficacitatea tratamentului au crescut odat cu creterea concentraiei
colesterolului. Collaborative AtoRvastatin Diabetes
Study (CARDS), studiu clinic randomizat specific creat
pentru pacienii cu DZ tip 2 fr boal cardiovascular
manifest clinic, a demonstrat c scderea nivelului colesterolului seric cu atorvastatin 10 mg a determinat o
reducere a riscului de evenimente ischemice cardiace
i cerebrovasculare166. O serie de metaanalize au confirmat la pacientii diabetici beneficiile tratamentului
hipolipemiant cu ajutorul statinelor fa de placebo452.
Analiza unui subgrup de 1501 pacieni diabetici inclui n studiul Treating to New Targets (TNT), care a
comparat terapia intensiv cu 80 mg atorvastatin vs.
cea standard cu 10 mg de atorvastatin, a artat o reducere mai important a riscului de evenimente primare,
de evenimente cerebrovasculare i a tuturor tipurilor
de evenimente cardiovasculare n grupul de pacieni
tratai intensiv cu statine442.

Este necesar o prevenie agresiv i timpurie, utiliznd medicamente hipolipemiante, indiferent de nivelul intial al LDL colesterolului i avnd ca int un
nivel ct mai sczut al valorilor lipidice, n special la
pacienii cu DZ tip 2. Pentru pacienii cu DZ tip 2 care
asociaz boal cardiovascular sau boal cronic renal
sau au unul sau mai muli factori de risc cardiovascular, nivelul optim al LDL colesterolului ar trebui s fie
<1,8 mmol/L (~70 mg/dl). Trebuie subliniat faptul c
pacienii cu DZ tip 2 deseori au valori n limite normale sau numai uor crescute ale LDL colesterolului, n
timp ce un factor de risc pentru bolile cardiovasculare
la aceti pacienii diabetici l reprezint dislipidemia
caracterizat prin hipertrigliceridemie i valori sczute ale HDL colesterolului. Studii clinice ce au urmrit
posibilele beneficii ale tratamentului hipolipemiant cu
fibrai la pacienii diabetici au furnizat rezultate echivoce.
4.8.8 Terapia antitrombotic
Pacienii cu diabet zaharat tip 1 sau 2 prezint un
risc crescut de a dezvolta fenomene trombotice. Metaanaliza Antiplatelet Trialists Collaboration a demonstrat beneficiile terapiei antitrombotice la pacienii diabetici cu boal cardiovascular, cerebrovascular sau
alte forme de afeciuni aterotrombotice453. Studiile au
analizat date colectate de la ~4500 de pacieni diabetici
i au concluzionat c tratamentul antiagregant plachetar (cel mai frecvent cu Aspirin) a determinat o reducere semnificativ de 25% a riscului de evenimente
cardiovasculare.
Rolul aspirinei n cadrul preveniei primare rmne
nedovedit. n studiul HOT s-a observant o reducere
suplimentar a riscului de evenimente cardiovasculare majore prin adugarea a 75 mg aspirin la pacienii
diabetici, cu valori tensionale controlate eficient, cu
preul unei rate mai mari a sngerrilor majore nonfatale440. O analiz mai amnunit a Antithrombotic
Trialists Collaboration a demonstrat o scdere nesemnificativ cu 7% a evenimentelor vasculare la pacienii
cu risc nalt datorat prezenei diabetului zaharat454. O
metaanaliz recent a 6 studii clinice randomizate a
artat c nu exist o reducere semnificativ statistic a
riscului de evenimente cardiovasculare majore sau a
mortalitii de orice cauz la pacienii diabetici fr
boal cardiovascular cunoscut, la care s-a administrat aspirin fa de cei cu placebo sau fr aspirin443.
Aspirina a redus semnificativ riscul infarctlului miocardic la brbai, dar nu i la femei. Evidenele legate de
efectele nocive nu au fost dovedite.

4.8.9 Microalbuminuria i interveniile

multifactoriale
Microalbuminuria (excreia urinar a unei cantiti
de albumin de 30 pn la 300 mg/24h) anticipeaz
apariia nefropatiei diabetice manifeste la pacienii cu
diabet zaharat tip 1 sau 2, n timp ce proteinuria (>300
mg/24 de h) indic de obicei distrucie instalat a parenchimului renal. Att la pacienii hipertensivi ct i
la cei nonhipertensivi, microalbuminuria -chiar i cea
sub pragul utilizat n prezent- prezice evenimente cardiovasculare. ntre mortalitatea de cauz cardiovascular precum i non cardiovascular i raportul proteine/creatinin s-a stabilit o relaie direct proporional
n multiple studii. Microalbuminuria poate fi msurat
utiliznd bandelete de testare urinar rapid (se prefer
s nu se utilizeze mostrele din timpul nopii sau din
urina colectat pe 24 de ore datorit inacurateii tehnicii de recoltare) prin indexarea concentraiei albuminei
urinare la concentraia cretininei urinare. Pacietii cu
microalbuminurie sau proteinurie trebuie sa fie tratai
cu un IECA sau un sartan indiferent de TA de baz.
Studiul Steno-2 a randomizat 160 de pacieni cu risc
nalt cu DZ tip 2 i microalbuminurie ntr-un grup ce a
primit tratament convenional i un grup cu tratament
intens multifactorial incluznd medicaie hipoglicemiant, statine. IECA, alte antihipertensive, aspirin, i
msuri de schimbare a stilului de via (oprirea fumatului, activitate fizic, diet)455. Reducerea semnificativ la 4 ani a complicaiilor microvasculare i o scdere
important cu 53% a complicaiilor macrovasculare la
8 ani, a demonstrat beneficiile terapiei intensive multifactoriale455. O urmrire suplimentar a artat o reducere semnificativ a mortalitii cardiovasculare la 8
ani, asociat terapiei multifactoriale456.
Prin urmare pacienii cu risc nalt necesit tratament
polifarmacologic, multifactorial pentru a obine beneficii maxime.
inta obinuit pentru HbA1c a crescut de la
<6,5% la <7,0%
Aspirina nu mai este recomandat n cadrul terapiei de prevenie primar la pacienii diabetici.
Lacune rmase de elucidat
Principalul mod de a atinge inta terapeutic a
HbA1c fr cretere ponderal excesiv sau hipoglicemie nu a fost stabilit
Posibilele beneficii cardiovasculare aduse de
noile medicamente antidiabetice cu risc sczut
de hipoglicemie, ca de exemplu inhibitorii de
dipeptidil peptidaza-4, ce nu determin cretere

Vol. 24, No. 4, 2014
ponderal, sau agonitii receptorului glucagonlike peptidei 1, ce sunt asociai cu scdere ponderal, sunt actualmente n studii clinice.
4.9 Lipidele
Mesaje cheie
Valorile plasmatice crescute ale colesterolului i
LDL-colesterolului sunt printre principalii factori de risc pentru BCV.
Hipertrigliceridemia i HDL-colesterolul sczut
sunt factori de risc independeni pentru BCV.
Terapia cu statine are un efect benefic asupra
prognosticului BCV aterosclerotice.
4.9.1 Introducere
Studii genetice i patologice, observaionale i intervenionale, au stabilit rolul crucial al dislipidemiei, n
special al hipercolesterolemiei, n dezvoltarea BCV.
n plasma sanguin, lipidele cum sunt colesterolul i
trigliceridele sunt legate de diverse proteine (apoproteine), pentru a forma lipoproteine. HDL nu cauzeaz
ateroscleroz; dimpotriv, acesta are proprieti antiaterogene. n contrast, LDL, n special LDL mici i dense, sunt aterogene. Chilomicronii i lipoproteinele cu
densitate foarte mic (VLDL) nu sunt aterogene, dar
concentraiile crescute ale acestor lipoproteine bogate
n trigliceride pot provoca pancreatit.
4.9.2 LDL-Colesterolul
Cea mai mare parte a colesterolului din plasma sanguin este, n condiii normale, transportat de LDL
i, pentru un spectru larg al concentraiilor de colesterol, exist o asociere pozitiv puternic i gradat ntre
colesterolul total, LDL Colesterol i riscul de BCV457.
Aceast asociere se aplic la indivizii (femei i brbai)
fr BCV, ca i la pacienii cu boal stabilit.
Dovada c reducerea LDL colesterolului plasmatic
scade riscul de BCV este fr echivoc; rezultatele studiilor epidemiologice, ca i ale trialurilor cu endpointuri
angiografice i clinice confirm c reducerea LDL colesterol trebuie s fie o preocupare major n prevenia
BCV42.
Meta-analizele a multe studii arat o reducere clar a
BCV odat cu scderea LDL-colesterolului. Fiecare reducere cu 1,0 mmol/L a LDL-colesterolului este asociat cu scderea cu 20-25% a mortalitii cardiovasculare
i a infarctului miocardic non-fatal. Mai recent, studiile
au confirmat c scderea LDL-colesterolului la valori
1,8 mmol/L (~70 mg/dL) este asociat cu cel mai mic
risc de evenimente cardiovasculare recurente la populaiile la care se aplic prevenia secundar459. Prin urmare, pentru subiecii cu risc foarte nalt, nivelul int
al LDL-colesterolului ar trebui s fie 1,8 mmol/L (~70

Vol. 24, No. 4, 2014

Recomandri pentru managementul hiperlipidemiei

Recomandri
Nivelurile int recomandate la subiecii cu risc sczut sau moderat sunt < 5 mmol/L (mai puin dect ~190 mg/dL) pentru colesterolul plasmatic total
i < 3 mmol/L (sub ~115 mg/dL) pentru colesterolul LDL la subieci cu risc sczut sau moderat
La pacienii cu risc nalt de BCV, este recomandat o int a LDL-colesterol < 2,5 mmol/L (sub ~100 mg/dL)
La pacienii cu risc foarte nalt de BCV, inta LDL-colesterol recomandat este < 1,8 mmol/L (sub ~70 mg/dL) sau o reducere a LDL colesterol 50%
atunci cnd nivelul int nu poate fi atins.
Toi pacienii cu hipercolesterolemie familial trebuie considerai pacieni cu risc nalt i tratai cu terapie hipolipemiant.
La pacienii cu un SCA, tratamentul cu statine n doze mari trebuie iniiat n timpul spitalizrii.
Prevenia accidentului vascular cerebral non-hemoragic: tratamentul cu statine trebuie iniiat la toi pacienii cu boal aterosclerotic stabilit i la
pacienii cu risc nalt de a dezvolta BCV. Tratamentul cu statine trebuie iniiat la pacienii antecedente de accident vascular cerebral ischemic noncardioembolic.
Boala arterial ocluziv a membrelor inferioare i boala arterelor carotide sunt condiii cu risc echivalent BCI i terapia hipolipemiant este recomandat.
Statinele trebuie considerate ca medicamente de prim linie la pacienii cu transplant i dislipidemie.
Boala cronic de rinichi (stadiile 2-5, cu RFG <90 mL/min/1,73 m2) este considerat un echivalent de risc al BCI, iar inta LDL colesterolului la aceti
pacieni trebuie adaptat la gradul insuficienei renale.
Clasa
Nivelb GRADE
Refc
Puternic
457, 458
Puternic
459-461
Puternic
459, 462, 463
I
I
A
A
Puternic
Puternic
464, 465
466-468
Puternic
469, 470
Puternic
471, 472
IIa
Puternic
473
IIa
Puternic
474
SCA = sindrom coronarian acut; BCI = boal cardiac ischemic; BCV = boal cardiovascular; RFG = rata filtrrii glomerulare; LDL = lipoprotein cu densitate mic.
a
b
Nivelul de eviden
c
Referine
mg/dL), sau o reducere cu 50% din nivelul bazal al

LDL-colesterolului.
4.9.3 Apolipoproteina B
Deoarece nivelurile apoB (principala apoprotein
dintre lipoproteinele aterogene) au fost att de frecvent
msurate n cadrul trialurilor clinice n paralel cu LDLcolesterolul, apoB poate fi substituit LDL colesterol475,
dar nu contribuie suplimentar la evaluarea riscului.
Pe baza dovezilor disponibile, se pare c apoB este
un marker de risc similar cu LDL-colesterolul i un
semn superior al eficacitii tratamentului de scdere
LDL Colesterol476. De asemenea, se pare c exist mai
puine erori de laborator n determinarea apoB dect
a LDL-colesterol, n special la pacienii cu hipertrigliceridemie, iar laboratoarele ar putea oferi uor i ieftin
msurtori standardizate ale apoB. Totui, apoB nu este
msurat n prezent n cele mai multe laboratoare dar,
dac este msurat, aceasta ar trebui s fie <80 i sub
100 mg/dL pentru pacienii cu risc foarte nalt i respectiv cu risc nalt de BCV.
4.9.4 Trigliceridele
Hipertrigliceridemia este un factor de risc cardiovascular independent semnificativ, dar se pare c asocierea nu este la fel de puternic precum cea pentru hipercolesterolemie55. Riscul este asociat mai puternic cu
hipertrigliceridemia moderat dect cu cea foarte sever (>0,10 mmol/L sau ~900 mg/dL), care este, pe de alt
parte, un factor de risc pentru pancreatit. Totui, nu
exist studii randomizate care s ofere suficiente dovezi
pentru a stabili niveluri int pentru trigliceride.
n prezent, trigliceridele jeun >1,7 mmol/L (~150
mg/dL) continu s fie considerate ca un marker de risc
crescut, dar concentraiile 1,7 mmol/L nu sunt niveluri int bazate pe dovezi pentru terapie. Exist dovezi
c trigliceridele msurate postpradrial au valoare predictiv chiar mai bun, deoarece indivizii sunt n status
postprandial majoritatea timpului477. Totui, datorit
lipsei de standardizare, msurarea trigliceridelor postpradrial nu este recomandat.
4.9.5 HDL-Colesterolul
Concentraiile sczute de HDL-colesterol sunt asociate n mod independent cu un risc cardiovascular
crescut, motiv pentru care HDL-colesterolul este inclus
n noile diagrame SCORE478. Combinaia de trigliceride moderat crescute i concentraii sczute de HDL-colesterol este foarte frecvent la pacienii cu risc nalt i
diabet tip 2, obezitate abdominal, rezisten la insulin, i care sunt inactivi fizic. Este parte a unui model de dislipidemie caracterizat prin triada: trigliceride
crescute, prezena particulelor LDL mici i dense, foarte aterogene, i concentraii mici de HDL-colesterol.
Concentraiile sczute de HDL-colesterol pot rivaliza
chiar cu hipercolesterolemia (datorat concentraiilor
mari de LDL-colesterol), ca factor de risc pentru
BCV479. Cu toate acestea, nu exist nc suficiente dovezi tiinifice pentru ca, vreo valoare a HDL-colesterolului s fie considerat obiectiv terapeutic, dei valorile
HDL-colesterolul <1,0 mmol/L (~40 mg/dL) la brbai
i <1,2 mmol/L (~45 mg/dL) la femei pot fi considerate
markeri de risc crescut.
4.9.6 Lipoproteina (a)
Lipoproteina (a) este o lipoprotein cu densitate
mic la care este ataat o protein suplimentar numit apolipoproteina (a). Concentraiile mari de Lp(a)

sunt asociate cu un risc crescut de BCV i de accident

vascular cerebral ischemic, dei nu exist nici un studiu randomizat care s dovedeasc faptul c reducerea
Lp(a) scade riscul de BCV480. n prezent nu exist nici
o justificare pentru screening-ul populaiei generale
pentru Lp(a), i nici dovezi pentru o eventual valoare
int.
4.9.7 Raportul apolipoprotein B /
apolipoprotein A1
Apolipoproteina A1 (apoA1) este principala apoprotein din HDL. Fr ndoial c raportul apoB:apoA1
este unul dintre cei mai puternici markeri de risc475,
481
. Totui, nu s-a stabilit nc dac aceast variabil ar
trebui utilizat ca int a tratamentului. Deoarece msurarea apolipoproteinelor nu este disponibil pentru
toi medicii din Europa, este mai costisitoare dect
variabilele lipidice utilizate n mod curent, i nu ofer
informaii suplimentare, utilizarea sa nu este nc general recomandat.
4.9.8 Variabilele lipoproteice calculate
LDL-colesterolul
LDL-colesterolul poate fi msurat direct, dar de regul este calculat utiliznd formula Friedewald482:
n mmol/L: LDL-colesterol = colesterol total HDLcolesterol - (0,45 x trigliceride)
n mg/dL: LDL-colesterol = colesterol total HDLcolesterol - (0,2 trigliceride)
Calculul este valabil numai atunci cnd concentraia
de trigliceride este <4,5 mmol/L (400 mg/dL) deoarece raportul trigliceride/colesterol n lipoproteinele care
transport trigliceride (VLDL i chilomicroni) crete
progresiv pe msur ce hipertrigliceridemia crete n
severitate.
Non-HDL colesterolul
Non-HDL colesterolul este compus din LDL, lipoproteinele cu densitate intermediar, i particulele
VLDL. Non-HDL colesterolul are o valoare predictiv similar sau chiar superioar LDL-colesterolului,
pentru riscul de BCV483. Limitele LDL pot fi transferate limitelor non-HDL adugnd 0,8 mmol (30 mg/L).
Calculat prin simpla scdere a HDL-colesterolului din
colesterolul total, non-HDL colesterolul - spre deosebire de LDL-colesterol - nu necesit concentraii ale trigliceridelor <4,5 mmoli/L (~400 mg/dL). Prin urmare,
este o msur mai bun dect LDL-colesterolul calculat, n special la pacienii cu concentraii nalte de trigliceride postpradrial. Ca i apoB, colesterolul non-HDL
este o msur a concentraiei plasmatice de lipoprote

Vol. 24, No. 4, 2014
ine aterogene, dar este mai accesibil dect msurarea

apoB i apoA1.
4.9.9 Excluderea dislipidemiei secundare
Prezena dislipidemiilor secundare altor afeciuni
trebuie exclus naintea nceperii tratamentului medicamentos, deoarece tratamentul bolii de baz amelioreaz hiperlipidemia i nici o alt terapie antilipemic
nu este necesar. Acest lucru este valabil n special pentru hipotiroidism.
Dislipidemiile secundare pot fi, de asemenea, cauzate de abuzul de alcool, diabet, sindromul Cushing, boli
hepato-renale, ca i diverse medicamente (de exemplu,
corticosteroizi, isotretinoin i etretinat, ciclosporin).
Pacienii care ar putea avea dislipidemii genetice, cum
este hipercolesterolemia familial, trebuie trimii la
o evaluare de specialitate, care ar putea include i un
diagnostic de genetic molecular.
4.9.10 Cine ar trebui tratat i care sunt
obiectivele?
n general, colesterolul plasmatic total ar trebui s
fie <5 mmol/L (~190 mg/dL), iar LDL-colesterol <3
mmol/L (~115 mg/dL). La subiecii cu risc crescut de
BCV, obiectivele terapeutice trebuie s fie mai sczute
(vezi mai jos).
Cea mai mare prioritate pentru tratament sunt pacienii cu BCV indiferent de nivelurile lor lipidice484. La
aceti pacieni cu risc foarte nalt (vezi pagina 1653),
obiectivul LDL-colesterol este <1,8 mmol/L (mai mic
de ~70 mg/dL) sau o reducere a LDL-colesterolului cu
50% atunci cnd nivelul int nu poate fi atins.
La pacienii cu risc nalt de BCV (vezi pagina 1653),
ar trebui luat n considerare o int a LDL-colesterolui
<2,5 mmol/L (mai mic de ~100 mg/dL).
La subiecii cu risc moderat (un nivel SCORE 1
pn la <5%), ar trebui luat n considerare o int a
LDL-colesterol <3,0 mmol/L (mai puin de ~115 mg/
dL).
La persoanele asimptomatice, primul pas este de a
evalua riscul cardiovascular total i de a identifica factorii de risc care trebuie modificai42. Evaluarea riscului ar trebui repetat la intervale de 5 ani, dac riscul
absolut de BCV este sczut i/sau nu exist modificari
semnificative n valorile recomandate ale factorilor de
risc majori.
Evaluarea riscului total nu se refer i la pacienii cu
hipercolesterolemie familial, deoarece colesterolul total >0,8 mmol/L (~320 mg/dL) i LDL-colesterolul >0,6
mmol/L (~240 mg/dL) poziioneaz, prin definiie,
astfel de pacieni n zona de risc total nalt de BCV.
Hipercolesterolemia familial este o condiie moteni-

Vol. 24, No. 4, 2014
t transmis dominant, care afecteaz 1 din 500 de

persoane de origine european (heterozigoii), cel mai
frecvent cauzat de o mutaie a receptorilor LDL, i se
caracterizeaz prin niveluri foarte nalte de LDL-colesterol (de obicei 5-10 mmol/L sau 200-400 mg/dL)42.
Beneficiul terapiei de scdere a colesterolului depinde de nivelurile iniiale de risc: cu ct riscul este mai
nalt, cu att beneficiul este mai mare (Tabelul 16). Nu
exist diferene ale efectelor benefice n scderea colesterolului ntre brbai i femei, sau ntre tineri i vrstnici, inclusiv la indivizi >75 de ani, chiar dac beneficiile la femeile sntoase nu sunt dovedite485.
Dei HDL-colesterolul sczut este un factor de risc
independent pentru BCV, nu au fost definite nc
obiective specifice de tratament, dar ele pot fi considerate la <1,0 mmol/L (~40 mg/dL) la brbai i <1,2
mmol/L (~45 mg/dL) la femei. De asemenea, trigliceridele a jeun ar trebui s fie >1,7 mmol/L (~150 mg/dL).
4.9.11 Pacienii cu boal arterial periferic
Boal arterial ocluziv a membrelor inferioare i
boala arterial carotidian sunt echivalente ca risc cu
boala coronarian, iar terapia hipolipemiant este recomandat la aceti pacieni indiferent de nivelurile
lipidelor lor plasmatice472,486. Totui, grosimea intimmedia (IMT) carotidian crescut, fr evidenierea de
plci de aterom nu este o indicaie pentru tratamentul
hipolipemiant la pacienii fr BCV dovedit sau ali
factori de risc.
Dei anevrismul aortic abdominal este, de asemenea,
o condiie echivalent de risc, nu exist dovezi concludente c tratamentul cu statine reduce morbiditatea
i mortalitatea perioperatorie prin BCV la aceti pacieni220,487. Beneficiul tratamentului hipolipemiant n
ateroscleroza altor tipuri de artere (de exemplu, aa. retiniene) rmne a fi dovedit488.
4.9.12 Prevenirea accidentului vascular cerebral
Spre deosebire de observaiile anterioare, studii recente au demonstrat c nivelurile ridicate de colesterol
sunt un factor de risc pentru accidentul vascular cerebral ischemic, dar nu i pentru cel hemoragic489. Studiile majore cu statine au raportat reduceri semnificative ale ratelor de accident vascular cerebral la pacienii
cu BCI sau cu risc ridicat, datorit reducerii ratelor de
accident vascular cerebral ischemic469. Concentraiile
crescute de trigliceride, ca i HDL-colesterolul sczut
sunt asociate cu accidentul vascular cerebral non-hemoragic490,491. Prin urmare, pacienii cu boal cerebrovascular ischemic merit acelai grad de atenie al
tratamentului dislipidemiilor ca i pacienii cu BCI.

n prevenirea accidentului vascular cerebral, tratamentul cu statine ar trebui iniiat la toi pacienii cu
boal aterosclerotic dovedit, ca i la pacientii cu risc
crescut de dezvoltare a BCV. Dup un eveniment cerebrovascular, statinele trebuie iniiate la pacieni cu antecedente de accident vascular cerebral ischemic noncardioembolic sau de atac ischemic tranzitor pentru
prevenirea evenimentelor cardiovasculare viitoare, dar
ar trebui evitate dup accidentul vascular cerebral hemoragic, dac nu exist dovezi de boal aterosclerotic
sau risc nalt de BCV.
4.9.13 Pacienii cu boal renal
Boala renal cronic (BRC) se caracterizeaz prin
dislipidemie mixt (trigliceride crescute, LDL-colesterol crescut i HDL-colesterol sczut)492. Microalbuminuria este un factor de risc pentru BCV, care crete
progresiv de la o RFG normal i pn la boala renal
n stadiul final. BRC (stadiile 2-5, adic RFG <90 mL/
min/1,73 m2) este recunoscut ca avnd un risc echivalent BCI, iar inta LDL-colesterolului la aceti pacieni
a fost adaptat la gradul insuficienei renale (vezi pagina 1653)42.
Doza de statin ar trebui modificat n funcie de
RFG. Tratamentul cu statine are un efect benefic asupra
prognosticului BCV n stadiile 2 i 3 i ncetinete rata
deteriorrii funciei renale493.
4.9.14 Pacienii cu transplant
Dislipidemia este comun la pacienii care au suferit
transplant de organe datorit unei combinaii de factori legai de boala de baz, stilul de via, i tratamente, inclusiv imunosupresoare. Managementul riscului
cardiovascular este o prioritate la aceast populaie
de pacieni, iar farmacoterapia este adeseori necesar.
Statinele sunt recomandate ca medicamente de prim
linie.
Iniierea ar trebui s fie cu doze mici, apoi cu titrare
atent i prudent n ceea ce privete potenialele interaciuni medicamentoase, n special la cei care primesc
ciclosporin. n cazul pacienilor intolerani la statine
sau care au dislipidemie semnificativ i un risc rezidual nalt n pofida administrrii dozei maxime tolerate
de statine, poate fi luat n considerare o terapie alternativ sau adiional: ezetimib pentru cei cu LDL-colesterol ridicat ca i caracteristic principal, fibrai (cu
pruden n cazul combinaiei cu o statin), sau niacin
pentru cei cu hipertrigliceridemie i/sau HDL-colesterol sczut494.

4.9.15 Pacienii cu sindrom coronarian acut

La toi pacienii cu un SCA, tratamentul cu statin n
doze mari trebuie iniiat ct mai curnd posibil, n timpul internrii, cu scopul de a atinge un nivelul al LDLcolesterol <1,8 mmol/L (~70 mg/dL)466,467. Tratamentul
medicamentos precoce trebuie combinat cu modificri
eficiente ale stilului de via i, n special, consiliere dietetic dup externare. Lipidele sanguine ar trebui verificate la 4-6 sptmni dup SCA pentru a determina
dac nivelul int a fost atins i dac tratamentul trebuie continuat cu aceeai doz sau doza trebuie adaptat
n consecin.
4.9.16 Medicamente
Medicamentele hipolipemiante disponibile n prezent includ inhibitori ai 3-hidroxi-3-metilglutaril-coenzima A reductaz (statine), fibrai, chelatori de acizi
biliari (rini schimbtoare de anioni), niacina (acid
nicotinic), i inhibitori selectivi ai absorbiei colesterolului (de exemplu, ezetimib).
Statinele, prin scderea LDL colesterolui, reduc morbiditatea i mortalitatea cardiovasculare, precum i necesitatea interveniilor pe arterele coronare166, 436. Statinele n doze care reduc n mod eficient LDL-colesterolul cu 50% par, de asemenea, s stopeze progresia sau
chiar s contribuie la regresia aterosclerozei coronariene495. Prin urmare, ele ar trebui utilizate ca medicamente de prim alegere la pacienii cu hipercolesterolemie
sau dislipidemie mixt.
Activitatea plasmatic crescut a enzimelor hepatice apare ocazional, i, n cele mai multe cazuri este
reversibil: 5-10% dintre pacienii care primesc stati-

Vol. 24, No. 4, 2014
ne dezvolt miopatie, dar rabdomioliza este extrem de

rar. Riscul de miopatie poate fi redus prin identificarea pacienilor vulnerabili i/sau evitarea interaciunii
statinelor cu medicamente specifice (Tabelul 17). Deoarece statinele sunt prescrise pe termen lung, posibilele interaciuni cu alte medicamente merit o atenie
deosebit i continu, deoarece multi pacieni primesc
farmaco-terapie pentru boli concomitente496.
n general, profilul de siguran al statinelor este
acceptabil i, observaiile mai vechi potrivit crora tratamentul hipolipemiant ar putea contribui la creterea
mortalitii non-cardiovasculare (de exemplu, cancere,
suicide, depresie) sau tulburri mentale, nu au fost confirmate. Au fost raportate creteri ale nivelurilor glicemiei i HbA1c, adic risc crescut de diabet tip 2, ca posibil efect advers al terapiei cu statine pe termen lung, dar
beneficiile statinelor depesc cu mult riscurile pentru
marea majoritate a pacienilor497,498.
Tratamentul non-statine: inhibitorii selectivi ai absorbiei colesterolului nu sunt utilizai ca monoterapie
pentru a reduce concentraiile de LDL-colesterol. i
chelatorii acizilor biliari reduc colesterolul total i LDLcolesterolul, dar au tendina de a crete concentraiile
trigliceridelor. Fibraii i niacina sunt utilizate n primul rnd pentru scderea trigliceridelor i creterea
HDL-colesterolului, n timp ce uleiurile de pete (acizii
grai omega-3) n doze de 2-4 g/zi sunt utilizate pentru
scderea trigliceridelor479,499.
Cnd trigliceridele depesc 10 mmol/L (~900 mg/
dL), n scopul de a preveni pancreatita, trigliceridele
trebuie reduse nu numai prin medicamente, dar i prin
Tabelul 16. Strategii de intervenie n funcie de riscul CV total i nivelul LDL colesterolului
Risc CV total
Niveluri LDL-C
(SCORE) %
< 70 mg/dL
Intre 70 i < 100 mg/dL
< 1,8 mmol/L
Intre 1,8 i < 2,5 mmol/L
<1
Fr intervenie pe lipide
Fr intervenie pe lipide
Intervenie pe stilul de via
Clasa/Nivelb
1 la < 5
I/C
Clasa/Nivelb
5 la < 10, sau risc nalt
I/C
Intervenie pe stilul de via, ia
n considerare medicamente
Clasa/Nivelb
10 sau risc foarte nalt
IIa/A
Intervenie pe stilul de via, ia
n considerare medicamente*
Clasa/Nivelb
IIa/A
Referin tabel.42
CV = cardiovascular; LDL = lipoprotein cu densitate mic.
a
Clasa de recomandare.
b
Nivelul de eviden.

> 190 mg/dL

> 4,9 mmol/L
Intervenie pe stilul de via,
medicamente dac nu se obine
nivelul dorit
I/C
I/C
I/C
IIa/A
medicamente dac nu se obine medicamente dac nu se obine medicamente dac nu se obine
nivelul dorit
nivelul dorit
nivelul dorit
I/C
IIa/A
IIa/A
I/A
Intervenie pe stilul de via, ia Intervenie pe stilul de via i Intervenie pe stilul de via i Intervenie pe stilul de via i
n considerare medicamente
terapie medicamentoas ncepu- terapie medicamentoas ncepu- terapie medicamentoas nceput imediat
t imediat
t imediat
IIa/A
IIa/A
I/A
I/A
Intervenie pe stilul de via i Intervenie pe stilul de via i Intervenie pe stilul de via i Intervenie pe stilul de via i
terapie medicamentoas ncepu- terapie medicamentoas ncepu- terapie medicamentoas ncepu- terapie medicamentoas nceput imediat
t imediat
t imediat
t imediat
IIa/A
I/A
I/A
I/A

Vol. 24, No. 4, 2014
restricia de alcool, controlul diabetului cu insulin,

ntreruperea terapiei estrogenice, etc. La rarii pacieni
cu hipertrigliceridemie primar sever este necesar
restricia absolut de alcool i restricia sever de lipide
cu caten lung, att de origine animal, ct i vegetal. Fibraii sunt medicamente de elecie pentru aceti
pacieni, iar acizii grai omega-3 pot fi adugai dac
trigliceridele crescute nu au sczut n mod adecvat.
Tabelul 17. Medicamente selecionate care pot crete riscul de miopatie i rabdomioliz atunci cnd sunt utilizate concomitent cu statinele
(inhibitori ai CYP3A4/substraturi sau alte mecanisme)
Ciclosporin, tacrolimus
Macrolide (azitromicin, claritromicin, eritromicin)
Azoli antifungici (itraconazol, ketoconazol, fluconazol)
Antagoniti de calciu (mibefradil, diltiazem, verapamil)
Nefazodon
Inhibitorii proteazei HIV (amprenavir, indinavir, nelfinavir, ritonavir, saquinavir)
Sildenafil
Altele: digoxin, niacin, fibrai (n particular gemfibrozil)
4.9.17 Combinaii medicamentoase

Pacienii cu dislipidemie, n particular cei cu BCV,
diabet, sau indivizii asimptomatici cu risc nalt, nu pot
atinge ntotdeauna obiectivele de tratament. De aceea,
tratamentul combinat poate fi necesar.
Combinaiile dintre o statin i un chelator de acizi
biliari, sau cea dintre o statin i ezetimib, pot fi folosite
pentru a obine o reducere mai mare a LDL-colesterolului dect se poate realiza cu un singur medicament.
Un alt avantaj al terapiei combinate este reducerea
dozelor de statine utilizate, diminund astfel riscul
efectelor adverse asociate cu dozele mari. Cu toate
acestea, nainte de terapia combinat, statinele ar trebui
utilizate n cele mai mari doze tolerate pentru a atinge
inta LDL-colesterol500.
Combinaiile de niacin cu o statin cresc HDL-colesterolul i scad trigliceridele mai bine dect oricare
dintre aceste medicamente singure, dar administrarea
niacinei poate prezenta ca principal efect advers flushing-ul, care poate afecta compliana. Adugarea de
laropiprant la niacin ar putea ajuta la reducerea incidenei acestui efect advers.
Fibraii, n special fenofibratul, pot fi utili nu numai
la reducerea concentraiilor mari ale trigliceridelor i
creterea HDL-colesterolului, dar i la scderea suplimentar a LDL-colesterolului prin co-administrare cu
o statin. Alte medicamente metabolizate prin intermediul citocromului P450 trebuie evitate atunci cnd
aceast combinaie este prescris. Pentru a reduce concentraiile de vrf i riscul de miopatie, fibraii ar trebui administrai, de preferin, dimineaa, i statinele

seara. Pacienii trebuie instruii despre simptomele de

avertizare (mialgii), chiar dac aceste efecte adverse
sunt foarte rare. Se mai recomand evitarea adugrii
gemfibrozil la un tratament cu statine.
Dac nivelurile int nu pot fi atinse nici chiar la dozele maxime ale terapiei hipolipemiante, inclusiv combinaii medicamentoase, pacienii vor beneficia totui
de tratament n msura n care dislipidemia a fost ameliorat. La aceti pacieni, o atenie sporit spre ali factori de risc poate ajuta la reducerea riscului total.
4.9.18 Afereza LDL
Pacieni rari, cu hipercolesterolemie sever, n special hipercolesterolemie familial homozigot, necesit o evaluare de specialitate pentru afereza LDL. Prin
aceast tehnic pretenioas i costisitoare, dar deopotriv eficient, LDL este eliminat din plasm n timpul
circulaiei extracorporale, sptmnal sau la dou sptmni. Afereza LDL ar trebui combinat cu tratamentul cu medicamente hipolipemiante.
LDL-colesterolul este recomandat ca analiz primar a lipidelor pentru screening i estimarea
riscului, precum i ca int pentru tratament.
HDL-colesterolul este, de asemenea, un factor de
risc puternic i se recomand a fi utilizat pentru
estimarea riscului, dar nu i ca int pentru tratament.
Lacune rmase
Nu exist nc suficiente dovezi pentru a considera o valoare a trigliceridelor sau HDL-colesterolului ca i int terapeutic care ar reduce
evenimentele cardiovasculare i mortalitatea.
Nu exist nc suficiente dovezi pentru a dovedi
dac scderea Lp(a) pe fondul tratamentului cu
statine poate reduce riscul de BCV.
Non-HDL colesterolul este o msur mai bun
dect LDL-colesterolul calculat, dar nu exist
nc informaii despre implicaii practice.
Nu exist dovezi care s ateste c unele alimente
funcionale cu efect hipolipemiant pot reduce i
riscul de BCV.
Nu exist date suficiente pentru a dovedi dac
tratamentul combinat, cu diferite medicamente
hipolipemiante poate reduce riscul evenimente
de BCV i a mortalitii.

4.10 Antitromboticele
4.10.1 Terapia antiagregant plachetar la
indivizii fr boal cardiovascular manifest
Prevenia primar la indivizi fr boli cardiovasculare sau cerebrovasculare manifeste a fost investigat
folosind pe termen lung aspirin vs. control ntr-o analiz sistematic a ase studii clinice incluznd 95 000 de
persoane. A fost gsit o reducere a riscului de evenimente vasculare grave de la 0,57% la 0,51% pe an de
ctre Antithrombotic Trialists Collaboration507. Aceast
reducere proporional a riscului de 12% s-a datorat n
principal unei reduceri a infarctului miocardic non-fatal. A existat o uoar cretere a accidentului vascular
cerebral hemoragic i o reducere a accidentului vascular cerebral ischemic. Efectul net asupra accidentului
vascular cerebral nu a fost semnificativ statistic. Hemoragiile majore gastro-intestinale i extracraniale au
crescut cu 0,03% pe an. Riscul de mortalitate vascular
nu s-a schimbat prin tratamentul cu aspirin. Aspirina
nu poate fi recomandat n prevenia primar din cauza riscului crescut de sngerri majore. La persoanele
cu multipli factori de risc, clopidogrelul a fost testat vs.
aspirin n studiul CHARISMA (Clopidogrel for High
Athero-thrombotic Risk and Ischaemic Stabilization,
Management, and Avoidance) i nu a prezentat un beneficiu semnificativ514.
4.10.2 Terapia antiagregant plachetar
la indivizii cu boal cardiovascular sau
cerebrovascular manifest
n faza acut de ischemie cerebral, aspirina a redus
riscul de evenimente vasculare noi n decurs de 2-4
sptmni (RR = 0,78, 95% CI, 0,76-0,80) prin prevenirea a patru accidente vasculare cerebrale recurente i
cinci decese vasculare la 1000 de pacieni tratai515.
Ca urmare a unui episod de ischemie coronarian
acut (angina instabil, non-STEMI, STEMI), terapia
dual antiplachetar cu clopidogrel i aspirin a redus
riscul de infarct miocardic, accident vascular cerebral,
i deces dup 14 zile de la 10,1% la 9,2% (p = 0,002) n
STEMI [Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT)]504 i de la 6,4% la 4,5% (p =
0,03) pe parcursul unei perioade de 8 luni la pacienii
NSTEMI [Clopidogrel in Unstable Angina to Prevent
Recurrent Events (CURE)]505.
La pacienii cu SCA pentru care este planificat o
strategie invaziv precoce, terapia dual antiplachetar cu un inhibitor de P2Y12 (ticagrelor sau prasugrel)
adugat la aspirin a fost superioar clopidogrelului i
aspirinei. Cu ticagrelor administrat 12 luni, endpointul
compus din deces de cauz vascular, infarct miocar

Vol. 24, No. 4, 2014
dic, sau accident vascular cerebral, a sczut de la 9,8%

comparativ cu 11,7% la cei care au primit clopidogrel
(HR 0,84, 95% CI 0,77-0,92; p <0,001). Nu au fost sesizate diferene semnificative n rata sngerrilor majore501-503.
Cu prasugrel, obiectivul principal de eficacitate a
avut loc la 9,9% dintre pacieni, comparativ cu 12,1%
care au primit clopidogrel (HR 0,81, 95% CI 0,73-0,90;
p <0,001). Riscul sngerrilor majore a crescut cu prasugrel501.
n prevenia secundar pe termen lung dup infarct
miocardic, accident vascular cerebral, sau arteriopatie
periferic, aspirina este medicamentul cel mai studiat.
ntr-o metaanaliz a 16 studii cuprinznd 17 000 de indivizi, Antithrombotic Trialists Collaboration 2009507 a
constatat c administrarea aspirinei a fost asociat cu
evenimente vasculare serioase la 6,7% din pacieni pe
an vs. 8,2% la grupul de control. Riscul de accident vascular cerebral total a fost de 2,08% pe an vs. 2,59% (p =
0,002) i evenimente coronariene 4,3% pe an vs. 5,3%
(p = 0,0001). Aspirina a fost asociat cu o reducere de
10% a mortalitii totale (RR 0,90; 95% CI 0,82-0,99),
dar i cu un exces semnificativ de sngerri majore;
totui, beneficiile aspirinei au depit riscurile hemoragice.
La pacienii cu infarct miocardic vechi, accident
vascular cerebral, sau boal vascular periferic, clopidogrelul a fost testat comparativ cu aspirina n trialul
CAPRIE (Clopidogrel versus Aspirin in Patients at Risk
of Ischaemic Events)509, care a artat o uoar superioritate a clopidogrelului; rata de evenimente vasculare
serioase a fost de 5,32% pe an cu clopidogrel vs. 5,83%
cu aspirin (p = 0,043). Au fost puin mai multe sngerri cu aspirin.
Terapia dual antiplachetar cu clopidogrel plus aspirin vs. clopidogrel la pacienii cu atac ischemic tranzitor i accident vascular cerebral ischemic a fost asociat cu un exces de sngerri serioase n trialul MATCH
(Management of Atherothrombosis with Clopidogrel in
High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke)510, i nu este recomandat n
ischemia cerebral.
La pacienii cu accident vascular cerebral ischemic
non-cardioembolic vechi, terapia dual antiplachetar
cu dipiridamol plus aspirin a artat superioritate fa
de aspirin511. La aceti pacieni antagonitii orali ai vitaminei K nu sunt superiori aspirinei, dar se asociaz
cu un risc mai mare de sngerare512,513.
La pacieni cu accident ischemic tranzitor sau accident vascular cerebral ischemic, o comparaie direct

Vol. 24, No. 4, 2014

Recomandri pentru terapia antitrombotic

Recomandri
n faza acut a sindroamelor coronariene i pentru urmtoarele 12 luni se recomand terapia dual antiplachetar cu un inhibitor P2Y12 (ticagrelor sau prasugrel)
adugat aspirinei, dac nu exist contraindicaii cum ar fi riscul excesiv de hemoragie.
Clopidogrelul (600 mg doz de ncrcare, 75 mg doz zilnic) este recomanadt la pacienii care nu pot primi ticagrelor sau prasugrel.
n faza cronic (>12 luni) dup infarctul miocardic, aspirina este recomandat pentru prevenia secundar.
La pacienii cu atac ischemic tranzitor non-cardioembolic sau accident vascular cerebral ischemic, se recomand prevenia secundar fie cu dipiridamol plus
aspirin, fie numai cu clopidogrel.
n cazul intoleranei la dipiridamol (cefalee) sau clopidogrel, se recomand doar aspirin.
La pacienii cu evenimente ischemice cerebrale non-cardioembolice, anticoagularea nu este superioar aspirinei i nu este recomandat.
Aspirina sau clopidogrelul nu pot fi recomandate la indivizii fr boal cardiovascular sau cerebrovascular, datorit riscului crescut de sngerare major.
Clasa
Nivelb GRADE
Refc
Puternic 501-503
Puternic
Puternic
Puternic 508-511
Puternic
III
Slab
III
Slab
504,
505
506,
507
506,
507
512,
513
507
SCA = sindrom coronarian acut; BCI = boal cardiac ischemic; BCV = boal cardiovascular; RFG = rata filtrrii glomerulare; LDL = lipoprotein cu densitate mic.
a
b
Nivelul de eviden
c
Referine
ntre dipiridamol plus aspirin vs. clopidogrel508 a artat pentru cele dou regimuri rate similare de accident
vascular cerebral recurent, inclusiv accident vascular
cerebral hemoragic (916 vs. 898; HR 1,01, 95% CI 0,921,11). A existat o frecven mai mare a evenimentelor
hemoragice majore cu dipiridamol plus aspirin (4,1%
vs 3,6%). Accidentul vascular cerebral, infarctul miocardic, i decesul de cauz vascular au avut loc n
13,1% n ambele grupuri. Cele dou regimuri pot fi
considerate echivalente.
n cele din urm, pentru orientarea utilizrii medicamentelor cardioprotectoare dup sindroame coronariene acute, ne referim la ghidurile existente pentru
aceast condiie; nu ne ocupm de aceast tem n ghidul de prevenie.
4.10.3 Tratamentul antitrombotic n fibrilaia
atrial
Accidentul vascular cerebral este cea mai serioas
complicaie a FA. FA este adesea nerecunoscut i netratat la pacienii internai cu accident vascular cerebral ischemic. Recomandrile pentru terapia antitrombotic ar trebui s se bazeze pe prezena (sau absena)
factorilor de risc pentru accident vascular cerebral i
tromboembolism, i ne referim aici la recentele ghiduri
ale grupului de lucru pentru managementul fibrilaiei
atriale din cadrul Societii Europene de Cardiologie516,517.
La pacienii cu SCA, terapia dual antiplachetar
cu un inhibitor de P2Y12 plus aspirin este superioar combinaiei clopidogrel plus aspirin.
Lacune rmase
Experiena pe termen lung cu noile medicamente
antiagregante plachetare este nc limitat.
4.11 Aderena
Mesaje cheie
Aderena la medicaie la persoanele cu risc nalt
i la pacienii cu BCV este nc sczut.
Mai multe tipuri de intervenii sunt eficiente n
ameliorarea aderenei la medicamente.
Recomandri cu privire la aderena pacienilor
aClasa de recomandare
bNivelul de eviden
cReferine
4.11.1 De ce pacienii nu ader la medicaia
prescris?
Numeroase studii au artat c aderena la medicamente la indivizii cu risc nalt i la pacienii cu BCV
este sczut, ducnd la agravri i la creterea costurilor pentru asisten medical. De exemplu, la o lun
dup un infarct miocardic acut, 25-30% dintre pacieni
opresc cel puin un medicament, cu un declin progresiv
al aderenei n timp. Dup un an, < 50% dintre pacieni
raporteaz utilizarea constant de statine, beta-blocante, sau antihipertensive518,519.
Motivele pentru aderena redus sunt multifactoriale. Dup cum se subliniaz n Tabelul 18, OMS a clasificat posibilele motive pentru non-aderena la medicamente n cinci mari categorii, care includ factori legai de sistemul de sntate, boal, pacient, terapie, i
factori socio-economici518.

Tabelul 18. Motive pentru lipsa aderenei la medicaie potrivit
Organizaiei Mondiale a Sntii518
Categoria de non-aderen
Exemplu
Sistemul de sntate
Calitate slab a relaiei furnizor-pacient; cunoatere redus a
medicaiei i/sau acceptare redus a ghidurilor; comunicare
slab (ex. limitat, complex sau confuz); accesibilitate
redus la serviciile medicale; lipsa continuitii ngrijirii.
Afeciune
Boal cronic asimptomatic (lipsa simptomelor fizice);
comorbiditi psihiatrice (ex. depresia).
Pacient
Deficite fizice (ex. tulburri de vedere sau alterri ale dexteritii); deteriorare cognitiv; factori psihologici/comportamentali (ex. lips de motivaie, eficien redus, impulsivitate);
vrst tnr.
Terapia
Complexitatea regimului; efecte secundare.
Factori socio-economici
Analfabetism; costuri mari ale medicamentelor; susinere
social slab.
Non-aderena legat de costul medicamentelor este

o problem relevant n multe sisteme de sntate, n
special la vrstnici i persoane cu statut socio-economic
sczut. De exemplu, la veteranii americani, aderena
la medicamentele hipolipemiante a sczut pe msur
ce co-plata a crescut521. Chiar i punerea n aplicare a
Medicare Part D, n scopul de a cheltui pe nevoile de
baz, nu a putut reduce non-aderena la cei mai bolnavi beneficiari. De asemenea, depresia dubleaz riscul
non-aderenei la medicamente, chiar i dup ajustarea
pe categorii de vrst, etnie, nivel de educaie, susinere
social, precum i severitatea bolii cardiace522.
Motivele pentru lipsa aderenei tind s se grupeze;
de exemplu, regimurile cu medicaie complex pot fi
importante la persoanele cu boli cronice, asimptomatice sau multipli factori de risc, care sunt lipsite de motivaie i fr o nelegere clar a regimului terapeutic.
Aceast situaie duce la responsabiliti medicale sporite: sftuire explicit i clar i ngrijire continu519. Cu
toate acestea, medicii ar putea s nu comunice elemente cheie de utilizare a medicamentelor (de exemplu, posibilele efectele adverse, ct timp trebuie administrat
medicaia, precum i frecvena de administrare a dozelor)523. Astfel, este nevoie de instruire pentru medici
n sensul identificrii factorilor de risc pentru nonaderen, respectiv promovrii aderenei la medicaie.
O revizuire sistematic recent a artat c mai multe
tipuri de intervenii sunt eficiente pentru ameliorarea
aderenei n bolile cronice; cu toate acestea, dimensiunile efectelor asupra aderenei au variat, ca de altfel
i rezultatele medicale520. Doar solicitarea de reducere
a dozelor a dus la efecte puternice (dimensiunea efectului 0,89-1,20), dar i alte intervenii ca feedback-ul i
monitorizarea repetitiv (mrimea efectului 0,27-1,2),
sesiunile multiple de consiliere (mrimea efectului
0,35-1,13), i interveniile comportamentale combinate (mrimea efectului 0,43-1,20) au avut efecte variind
ntr-un spectru larg de la slab la puternic520.

Vol. 24, No. 4, 2014
n practica clinic, medicii ar trebui s evalueze aderena la medicaie, s identifice motivele pentru posibila non-aderen, i s promoveze aderena n conformitate cu principiile stabilite (Tabelul 19).
n plus, dup cum i aderena la placebo mbuntete supravieuirea524, medicii ar trebui s fie contieni
de faptul c aderena la medicaie poate reflecta, n general, mai bine comportamentul sntos. Prin urmare, ar trebui luate msuri pentru a mbunti aderena
i comportamentul sntos n general (vezi Seciunea
4.1).
Solicitarea de reducere a dozelor la persoane cu risc
crescut de BCV poate avea ca rezultat prescrierea farmacoterapiei combinate, polipilula525,526. Recent, un
studiu randomizat de faz II la indivizi de vrst medie
fr BCV a demonstrat c formula Polycap poate reduce convenabil multipli factori de risc527.
Tabelul 19. Recomandri pentru promovarea aderenei la medicamente

Dai sfaturi clare cu privire la beneficiile i posibilele efecte adverse ale medicaiei, ca i
durata tratamentului i momentul administrrii.
Luai n considerare obiceiurile i preferinele pacienilor.
Reducei dozele la doza minim fezabil.
ntrebai pacienii n termeni laici despre efectele medicamentelor n cazul lor, i discutai
posibilele motive de non-aderen (exemple fiind efectele adverse, ngrijorri).
Implementarea feedback-ului i monitorizrii repetitive.
n cazul lipsei de timp, introducei profesioniti instruii, medici i/sau asistente medicale, ori
de cte ori este necesar i posibil.
n cazul non-aderenei persistente, oferii sesiuni multiple de consiliere sau intervenii
comportamentale combinate.

Dovezile sugereaz c cerina de reducere a dozelor este cea mai eficient abordare singular
pentru consolidarea aderenei la medicaie.
Lacune rmase
Exist dovezi limitate cu privire la: care sunt
interveniile cele mai eficiente i la cine? (de
exemplu, tineri-btrni, brbai-femei, situaie
socio-economic ridicat-sczut).
Polipilula necesit o evaluare ulterioar nainte
de a putea fi considerat adecvat pentru utilizarea curent.
5. UNDE AR TREBUI S FIE INSTITUITE PROGRAMELE

DE PREVENIE A BCV?
Mesaj cheie
Boala cardiovascular este cea mai important
cauz unic de deces, att pentru brbai, ct i
pentru femei, i poate fi de cele mai multe ori
prevenit!


Vol. 24, No. 4, 2014
Recomandri privind furnizarea de programe

Recomandri
Clasa
Aciunile de prevenie a bolii cardiovasculare ar trebui
ncorporate n viaa cotidian a fiecruia, ncepnd cu
IIa
copilria timpurie i continund de-a lungul perioadei
adulte i a senescenei.
Nivelb GRADE
B
Puternic
Cea mai important informaie nou

Interzicerea fumatului n locurile publice, prin
lege, a condus la o scdere a incidenei infarctului miocardic.
Refc
528
5.1 Prevenia bolilor cardiovasculare n ngrijirea

primar: rolul asistentei medicale
Mesajul-cheie
Programele de prevenie coordonate de asisteni
medicali sunt eficiente ntr-o varietate de situaii
practice.
Nivelul de eviden
c
Referine
a
b
Introducere
Dup cum s-a menionat n seciunea 2, prevenia
BCV este o abordare pe via, cu debut ideal nainte de
natere prin educarea tinerilor prini, i continund
la vrsta pre-colar (grdini) i de-a lungul claselor
avansate ale sistemului colar. n timpul acestei faze,
accentul ar trebui pus pe transmiterea plcerii pentru
alimentaia sntoas, i a bucuriei i sentimentului de
bunstare asociate activitii fizice, mai degrab dect
pe prevenirea explicit a bolii. ncepnd cu clasa a asea
(vrsta de 11-12 ani sau chiar mai devreme, n funcie
de mediul social), comportamentul non-fumat trebuie
ncurajat activ.
La grupul de vrst adult n funcie de sistemul
de ngrijiri de sntate, sunt disponibile diferite opiuni
pentru a promova prevenia ajustat dup risc: activiti
de nursing n comunitate, eforturi de prevenie ale medicilor generaliti i ale cardiologilor practicieni, programe centrate pe spital, i programe bazate pe societatea civil.
n plus, activiti legislative, cum sunt limitarea utilizrii acizii grai trans sau protejarea nefumtorilor de
fumatul pasiv (second-hand), interzicerea comerului
cu tutun, ca i programe de cretere a contientizrii
factorilor de risc produse de organizaii non-guvernamentale i societi medicale, se pot completa reciproc
n mod ideal n lupta pentru o populaie sntoas.
Dup un eveniment cardiovascular, eforturile de
prevenie secundar structurate n cadrul unui program de reabilitare s-au dovedit a fi deosebit de importante i cost-eficiente.
Toate aceste programe sunt componente importante
pentru prevenirea BCV, dar pentru a mbunti starea
de sntate a cetenilor comunitilor noastre nu ne
putem baza numai pe sistemul nostru de sntate; dup
cum au formulat Brown i OConnor: Avem nevoie s
crem comuniti sntoase i s ncorporm prevenia
n viaa cotidian, att ca furnizori de servicii medicale,
ct i ca ceteni529.
Recomandri pentru ngrijirea coordonat de asistentul medical

Recomandri
Clasa Nivelb GRADE Refc
Programele de prevenie coordonate de asisteni
35, 530,
medicali ar trebui s fie bine integrate n sistemele
IIa
B
Puternic
531
de sntate.
Nivelul de eviden
c
Referine
a
b
Modelele de caz care au beneficiat de management

din partea asistentului medical, fiind testate n mai multe studii randomizate de prevenie secundar, au artat
mbuntiri semnificative ale factorilor de risc, toleranei la efort, controlului glicemiei, i utilizarea medicaiei adecvate, mpreun cu scderea evenimentelor
i a mortalitii cardiace, regresia aterosclerozei coronariene, i mbuntirea percepiei despre sntate a pacientului, comparativ cu ngrijirea obinuit530, 531. Alte
studii au demonstrat eficacitatea preveniei condus de
asistente n ngrijirea primar, comparativ cu ngrijirea
obinuit, cu un succes mai mare n prevenia secundar versus prevenia primar532-534.
5.1.1 Programe de prevenie coordonate de
asisteni medicali eficiente n diferite sisteme de
sntate
Un program de prevenie multidisciplinar coordonat de asisteni medicali, desfurat att n spitale, ct
i n cabinetele de ngrijire primar a fost evaluat n
trialul EUROACTION, care a studiat pacieni cu BCI
i cu risc nalt de BCV din opt ri35. Abordarea a fost
centrat pe familie i a dus la un stil de via mai sntos cu schimbri n ceea ce privete dieta i activitatea
fizic, i un control mai eficient al factorilor de risc cum
este tensiunea arterial, att la pacieni ct i la partenerii lor, n braul de intervenie, comparativ cu ngrijirea obinuit. Un punct forte special al programului
a fost demonstrarea fezabilitii acestui tip de program
n spitale i n cabinetele de medicin general, n afara
centrelor specializate, i n opt sisteme de sntate din
ntreaga Europ.

S-au gsit diferene n ceea ce privete gradul de eficien a diferite programe conduse de asistente, ceea
ce ar putea reflecta o doz inadecvat a interveniei,
inconsistene ale componentelor interveniei, sau lipsa competenei specifice, ca i dificultile inerente n
obinerea unor modificri semnificative ale mai multor
factori. n cazurile la care s-a realizat o ngrijire mai intensiv s-au observat rezultatele cele mai de succes, inclusiv regresia aterosclerozei i scderea evenimentelor
cardiace535. Studiul EUROACTION a constat din opt
vizite ale unei echipe multidisciplinare, ca i participarea la un workshop de grup i exerciii supravegheate
pe o perioad de 16 sptmni; alte studii au evaluat
intervenii pe o durat mai scurt.
5.1.2 Legtura continu este necesar pentru
schimbarea stilului de via
Strategiile utilizate n diverse studii pentru a obine
modificarea comportamental i un stil de via sntos
au inclus evaluarea individualizat, comunicarea riscului, luarea deciziilor mpreun cu pacientul, participarea
familiei, stabilirea obiectivelor, educaia individual i
de grup, i interviul motivaional. Datorit diferenelor
n intensitatea, durata i componentele interveniei din
aceste studii, doza optim de contact sau componentele cele mai eficiente i cost-eficiente necesare pentru
rezultate pe termen lung nu sunt cunoscute, i nici modul n care acestea pot varia n funcie de caracteristicile pacientului. Tipul i durata de formare a asistentelor medicale n vederea interveniei sunt, de asemenea, diferite n aceste studii, ca de altfel i implicarea
n echipe multidisciplinare. Succesul interveniilor, n
ciuda acestor diferene, susine conceptul de baz potrivit cruia contactul mai susinut este necesar pentru
a realiza schimbri n stilul de via i mbuntirea
complianei. Sunt necesare cercetri suplimentare pentru a determina formatul optim al interveniilor necesare pentru a realiza reducerea susinut a riscului, i
modul n care acestea pot fi titrate i adaptate pentru
persoanele cu diverse riscuri i nevoi de asisten medical ntr-o varietate de situaii din unitile de ngrijire
medical i din comunitate. Dei exist dovezi c este
posibil ca aceste modele s fie rentabile536,537, este nevoie
de evaluare ulterioar, aa cum este cazul i n marea
provocare legat de comunicarea riscului i modificarea comportamentelor n prevenia primar.
Un document recent de consens realizat de Preventive
Cardiovascular Nurses Association, the Council of Cardiovascular Nursing and Allied Professions (CCNAP), i
Cardiovascular Nursing Council din cadrul AHA, a emis
un apel la aciune pentru asistenii medicali pentru mai

Vol. 24, No. 4, 2014
mult activitate n prevenia BCV531. Acest document

analizeaz necesitatea de prevenie la nivel mondial,
programe bazate pe dovezi coordonate sau conduse de
asisteni medicali, prevenia pe tot parcursul vieii, politici de sntate public i la multiple niveluri, precum
i pregtirea asistenilor medicali n asumarea de roluri
active n prevenia BCV.
Evidenele arat c managementul de caz efectuat de
asisteni medicali i programele multidisciplinare de
prevenie coordonate de asisteni medicali sunt mai eficiente dect practicile curente n reducerea riscului cardiovascular, i pot fi adaptate la o varietate de situaii de
asisten medical. Asistenii medicali cuprind o mare
parte a forei de munc din domeniul sntii, i, n
multe ri, formarea lor include un modul de pregtire
centrat pe educaia i consilierea pacientului, pe comunicare, ca i pe realizarea schimbrii comportamentale,
aptitudini necesare pentru programele de prevenie. De
asemenea, asistenii medicali sunt percepui de public
ca surse credibile de informaii i ajutor, iar rolurile lor
includ n mod tipic coordonarea ngrijirilor i colaborarea cu multipli furnizori. O provocare n Europa pentru acest tip de program este heterogenitatea diverselor
sisteme de sntate, heterogenitatea educaiei i a practicii asistenilor medicali n diferite ri, ca i acceptarea faptului ca asistenii medicali s-i asume responsabiliti dincolo de cele tradiionale. Cu toate acestea,
nevoia de programe eficiente pentru prevenie este de
netgduit, iar dovezile arat c asistenii medicali pot
conduce sau coordona astfel de sisteme ntr-o varietate
de situaii.
Cea mai important informaie nou
Programele multidisciplinare de prevenie conduse sau coordonate de asisteni medicali sunt
mai eficiente dect practicile curente n reducerea riscului cardiovascular, ntr-o varietate de
situaii de asisten medical.
Lacune rmase
Intensitatea optim (i cea mai cost-eficient) i
durata componentelor individuale ale interveniei trebuie stabilite pentru a obine reducerea
durabil a riscului la pacienii cu risc nalt sau cu
boli vasculare.
Cercetarea este, de asemenea, necesar pentru a
determina cunotinele i aptitudinile necesare
pentru programe eficiente de prevenie, ca i
educaia necesare pentru a asigura competena.

Vol. 24, No. 4, 2014
5.2 Prevenia bolilor cardiovasculare n practica

general
Mesaje cheie
Screeningul factorilor de risc incluznd profilul
lipidic poate fi luat n considerare la brbaii 40
de ani i la femeile 50 de ani sau postmenopauz42.
Medicul generalist este persoana cheie n iniierea, coordonarea i urmrirea pe termen lung a
persoanelor pentru prevenirea bolilor cardiovasculare538.
Medicii generaliti au o importan deosebit n implementarea i succesul programelor Europene de prevenie a BCV. In majoritatea rilor ei efectueaz peste
90% din consultaii i asigur cea mai mare parte a medicinii legat de sntatea public (prevenie, screeningul bolilor, monitorizarea bolilor cronice i urmrirea
lor). In cazul preveniei bolilor cardiovasculare ei au un
rol unic n indentificarea indivizilor la risc de BCV, dar
fr BCV stabilit, precum i n evaluarea necesitii de
intervenie n funcie de riscul lor cardiovascular.
5.2.1 Identificarea persoanelor la risc
In ciuda importanei crescute a BCV, muli pacieni
rmn nediagnosticai i netratai. Chiar i la pacienii
cu BCV diagnosticate, exist lacune substaniale n ceea
ce privete tratamentul; dintre pacienii care primesc
tratament hipolipemiant, 43% nu ating intele colesterolului total (<4,5 mmol/L, 175 mg/dL) n Europa5, n
timp ce 64% nu ating intele recomandate pentru LDL
colesterol n USA593. Exist de asemenea o problem a
managementului defectuos i o mic mbuntire n
timp a altor factori de risc cardiovascular precum fumatul, HTA i obezitatea540.
Performana n ceea ce privete prevenia primar a
bolilor cardiovasculare este chiar mai slab, cel putin
parial din cauza dificultilor de a identifica indivizii
cu risc mai nalt care ar putea beneficia de intervenii
terapeutice. Calcularea riscului cardiovascular global
implic nlocuirea clasicei clasificri de risc dicotomizat (da sau nu, prezent sau absent) cu conceptul
continuumului riscului n dezvoltarea evenimentelor
cardiovasculare, folosind diagramele SCORE (vezi Seciunea 3.1.3.). Majoritatea sistemelor actuale de calcul
al riscului cardiovascular se axeaz pe riscul pe termen
scurt (la 5 sau 10 ani), i astfel, inevitabil, este mai probabil ca vrstnicul s fie clasificat la risc nalt i tnrul la risc sczut. Dezvoltarea unor metode de calcul
al riscului pe toat viaa are scopul de a asigura o alt
metod de determinare a riscului care este mai puin

dependent de vrst. Prezentarea riscului relativ n

opozitie cu cel absolut reprezint o alt optiune pentru
discutarea riscului cardiovascular cu pacienii tineri.
5.2.2 Utilizarea scorurilor de risc n practica
clinic
Mai multe studii au investigat folosirea regulilor de
predicie i a metodelor de calcul a riscului cardiovascular de ctre medicii de medicin general. Un studiu ESC desfurat n 6 ri europene indic de ce medicii se bazeaz pe experiena proprie n prevenia i
tratamentul BCV: dei majoritatea cardiologilor i a
medicilor (85%) tiau c evaluarea riscului de BCV ar
trebui s se bazeze pe o combinaie a tuturor factorilor de risc cardiovascular, 62% dintre medici au folosit
metode subiective pentru a evalua riscul mai degrab dect s foloseasc scorurile de risc541. Obstacolele
cele mai frecvente n implementarea ghidurilor au fost
politicile locale i guvernamentale (40%), compliana
pacienilor (36%), i lipsa de timp (23%). Propunerile
sugerate pentru a mbuntii implementarea au inclus
dezvoltarea unor ghiduri clare, simple i usor de folosit
(46% solicitau; 23% nu solicitau) i stimulente financiare (24% nu solicitau).
Dei preferate de muli medici, evaluarea intuitiv
bazat pe experiena proprie pare a subestima riscul
real de BCV: medicii (110 generaliti i 29 interniti)
au estimat un risc de BCV mai mic dect cel obinut
prin recomandrile detaliate oferite de OMS - ghidurile Societii Internaionale de Hipertensiune542,543. Mai
mult, medicii au fost mai puin dispui de a prescrie
antihipertensive la pacieni identificai ca eligibili pentru tratament n ghiduri.
5.2.3 Obstacole n implementarea evalurii de
rutin a riscului cardiovascular
Pe lng limitrile impuse de nsi metoda de calcul al riscului, au fost identificate de ctre medici mai
multe obstacole n implementarea metodelor actuale
de evaluare a riscului. Un sondaj printre medicii specialiti de medicina general i medicin intern din
dou regiuni din Elveia a artat faptul c 74% dintre
ei au folosit foarte rar sau niciodat metodele de estimare a riscului de BCV544, datorit grijii de a simplifica prea mult evaluarea riscului (58%) sau de o folosire
exagerat a terapiei medicamentoase (54%). Mai bine
de jumtate dintre specialiti (57%) au fost de prere c
rezultatul numeric obinut prin metodele de predicie
este frecvent nefolositor n luarea deciziilor medicale544.
Un studiu olandez despre folosirea scorurilor de predicie ca o component cheie n evaluarea riscului n
prevenia primar, a artat faptul c nivelul de cunoa

tere al medicilor despre scorurile de risc i abilitatea de

a comunica pacientului rezultatele aferente a influenat
implementarea acestor metode545.
Pacienii pot avea o nelegere limitat n ceea ce
privete scorurile de risc i modul n care acest risc se
coreleaz cu dezvoltarea bolii546. Dezvoltarea de materiale educaionale pentru pacieni poate mbunti
nelegerea acestora i poate, de asemenea, s faciliteze
comunicarea medic- pacient. Durata obinuit a consultaiilor, care las puin timp pentru discuii, este recunoscut ca fiind o barier pentru realizarea estimrii
riscului545,547.
Medicii sunt de asemenea preocupai de o posibil
supraestimare a riscului la nivel naional, care poate
duce la o prescriere exagerat a tratamentelor medicale545,547. Rezultatele unui studiu norvegian sugereaz c
evaluarea prin grilele SCORE ar duce la dublarea numrului de persoane care au nevoie de medicamente
pentru prevenia primar a BCV548. Printre persoanele n cauz se numr brbaii i vrstnicii, la care ar
exista o probabilitate mai mare s aib nevoie de medicamente hipolipemiante. O cretere a numrului de
persoane care primesc medicamente poate duce la costuri mai mari pentru sistemul sanitar. Totui, realizarea
unor strategii pentru o folosire eficient a resurselor i
identificarea a 70% dintre persoanele cu risc de BCV
din Anglia, a artat c trierea pacienilor n funcie
de riscul lor cardiovascular poate duce la o scdere a
costurilor din sntate cu 45 000 n comparaie cu o
strategie de abordare primar a diabetului i a hipertensiunii arteriale547.
5.2.4 Metode pentru mbuntirea gradului de
contientizare i de implementare a calculrii
scorurilor de risc
Este necesar o cretere a contientizrii pacienilor,
a medicilor, a contribuabililor, i a politicienilor, inclusiv i prin presa scris, n ceea ce privete scorile de risc.
Observarea unui beneficiu personal este important
pentru muli pacieni. Imbuntirea implementrii
scorurilor de risc poate fi realizat utiliznd dou abordri principale: prin stimulente materiale i cu ajutorul calculatoarelor. Stimulentele s-au dovenit eficiente
n Anglia, unde rezultatul QOF (Quality and Outcome
Framework-Asociaia pentru monitorizarea Calitii i
a Rezultatelor) a artat c exist o strns legtur ntre
veniturile din asistena primar i obinerea unor inte specifice n ceea ce privete serviciile de sntate549.
QOF a introdus o form de remuneraie pentru realizarea scorului de risc n vederea preveniei primare la pacienii din registrul de hipertensiune din 2009.

Vol. 24, No. 4, 2014
Informarea prin intermediul calculatoarelor se poate

realiza prin trei tipuri de abordare, dar n mod ideal le
implic pe toate trei. Evaluarea individual de ctre pacient a riscului se poate realiza cu ajutorul programelor
on-line cum ar fi SCORE. Programele on-line de evaluare a riscului pot fi utilizate chiar dac nu sunt disponibile nivelul colesterolului din snge sau valoarea
tensiunii arteriale. Dezavantajul acestei metode const
n faptul c pacienii trebuie s fie foarte motivai i cunosctori n domeniul informaticii pentru a o folosi.
Evaluarea pacienilor cu risc nalt se poate face pe
baza unor date populaionale pre-existente, n urma
crora se ntocmete o list cu persoanele care au cea
mai mare probabilitate de a avea un risc nalt la o evaluare formal a riscului de apariie a bolilor vasculare,
ajutnd astfel medicii s reduc costurile evalund mai
nti aceti pacieni. Aceast metod necesit o baz de
date substanial a pacienilor i un sprijin financiar
semnificativ; totui ea, include toi pacienii i ofer o
metod raional de identificare a celor care ar putea
beneficia cel mai mult n urma acestei modaliti prioritare de tratament.
Metodele de calcul automat al riscului de BCV furnizeaz un scor de risc bazat pe datele extrase din dosarul electronic al pacientului. De exemplu, n Noua
Zeeland, mbuntirile din sistemul informatic din
cadrul medicinei primare a avut un real succes, ducnd
la o cretere a ratei de evaluare a riscului pentru BCV
de la 4,7% la 53,5% n decursul a 12 luni (n = 6570)550;
includerea unui sistem informatic de luare a deciziilor
(PREDICT-CVD) n programul electronic de nregistrare a datelor pacienilor, a mbuntit de 4 ori documentarea n ceea ce privete riscul cardiovascular ntro clinic de asisten primar cu 3564 de pacieni551.
Dezavantajul acestei metode este necesitatea de a avea
o baz de date electronic, faptul c informaiile adeseori lipsesc i lipsa de uniformitate n metoda de evaluare a scorului.
5.2.5 Imbuntirea managementului factorilor
de risc
Dei medicina general are, n majoritatea rilor,
un rol aparte n examinarea i identificarea pacienilor
eligibili pentru prevenie primar cardiovascular, asistena medical primar are de asemenea un rol esenial
n monitorizarea i urmrirea pacienilor identificai ca
avnd risc nalt i n intervenie la nevoie. Strategiile de
implementare pentru o aderen mai bun la sfaturile
n ceea ce privete modul de via i interveniile terapeutice, sunt comune n prevenia primar i n cea
secundar.

Vol. 24, No. 4, 2014

Barierele n implementarea unei prevenii n
funcie de gradul de risc sunt multiple: calcularea scorului de risc este considerat consumatoare de timp, simplificarea unei situaii complexe i
poate duce la administrarea excesiv de medicamente.
Resursele materiale folosite dup evaluarea acestui risc pot duce la scderea costurilor viitoare
din sistemul de sntate.
Lacune rmase
Calculul de rutin al scorurilor de risc de ctre
medicii de familie vs. tratamentul individual intit pentru un factor de risc, nu a artat o redudere a evenimentelor severe.
Evaluarea scorurilor de risc pe baza dosarului
electronic al pacientului este promitor dar necesit testare suplimentar.
5.3 Prevenia bolii cardiovasculare n ngrijirea
primar: rolul cardiologului
Mesaje cheie
Cardiologul trebuie s fie consultat n cazurile
n care prescrierea unui tratament medicametos preventiv este discutabil sau cnd opiunile
obinuite de prevenie sunt greu de pus n practic82,437,552.
Cardiologul ar trebui s verifice n mod regulat
recomandrile de la externare ale pacienilor care
au suferit un evenimet cardiac sau o intervenie
cardiac82,437,552.
5.3.1 Cardiologul n practica general: rol de
consultant
Cardiologii care lucreaz n afara spitalului au un
rol esenial n prevenirea bolilor cardiovasculare fiind
consultanii specialitilor din medicina general i intern. Cardiologul are un rol fundamental n evaluarea pacienilor cu probleme cardio-vasculare trimii de
medicul de familie. O examinare complet va include
adesea: testarea toleranei la efort, msurarea IGB, evaluarea structurii i a funciei cardiace prin ecocardiografie, i evaluarea pentru ateroscleroz preclinic cu
ajutorul ecografiei vasculare. Rezultatele examinrii
pot modifica semnificativ scorul de risc al pacienilor
cu risc aparent sczut.
Dei identificarea i tratamentul iniial al factorilor
de risc i sfaturile n legtur cu stilul de via sunt sarcinile specialitilor n medicin general i intern, cardiologul este consultantul n cazurile n care exist dubii n privina prescrierii tratamentului sau atunci cnd

metodele preventive sunt dificil de aplicat (de exemplu

n cazul dependenei de nicotin, obezitate rezistent,
efecte secundare ale tratamentului sau eficiena insuficient a tratamentului).
Se cere sfatul cardiologului i la pacienii la care se
pune n balan terapia de substituie hormonal cu
simptomele i cu riscul cardiovascular global. Sfatul
cardiologului este de asemenea necesar n cazul tratamentului cu medicamente antiagregante dup PCI la
pacienii care necesit anticoagulare oral (de exemplu
la pacienii cu FA sau la pacienii cu protez valvular
mecanic).
5.3.2 Implementarea medicinei bazate pe dovezi
Cardiologul este medicul care, pe baza recomandrilor actuale, revede mpreun cu pacientul recomandrile de la externare dup un eveniment cardiac sau
dup o intervenie cardiac i pune n aplicare strategia
de tratament ulterioar. Cardiologul l ajut pe pacient
s accepte recomandrile, prin oferirea lor n scris, i
asigurandu-se c la intervale date de timp sunt atinse
intele tratamentului82,522. Aceast abordare are un impact semnificativ asupra prognosticului pe termen mediu250,437.
Cu ct gradul de folosire al ghidurilor i a msurilor
de performan este mai mare, cu att impactul asupra preveniei i a evenimentelor recurente va fi mai
bun82,437.
5.3.3 Imbuntirea serviciilor medicale prin
folosirea unei baze de date electronice
Folosirea tot mai mare a datelor medicale electronice de ctre medicul cardiolog poate avea un impact
pozitiv n prevenirea bolilor cardiovasculare. Posibilitatea de a identifica pacienii cu factori de risc, de a se
documenta cu privire la barierele acestora n privina
ngrijirilor medicale i de a controla la intervale prestabilite gradul de implementare a reducerii riscului, ar
trebui s aduc rezultate favorabile. Exist o legtur
ntre acurateea acestor nregistrri, calitatea serviciului medical i aderena la aceste ghiduri437.
Ar trebui luat n considerare pregtirea medicului
cardiolog n a folosi aceste date electronice pentru implementarea i meninerea pe termen lung a strategiilor de prevenie. Pstrarea confidenialitii datelor este
important.
Cu ct ngrijirea pacienilor se bazeaz mai mult
pe ghiduri i pe msurile de performan, cu att
este mai bun impactul asupra preveniei i a evenimentelor recurente.


Vol. 24, No. 4, 2014
Lacune rmase
Impactul pozitiv a folosirii datelor electronice n
prevenia BCV prin mbuntirea comunicrii
dintre specialitii din diferite centre de sntate
trebuie s fie verificat i pus n balan cu pericolul de a pierde confidenialitatea acestor date.
5.4 Programe de autongrijire
Recomandri cu privire la programele de auto-ngrijire
Recomandri
Clasaa Nivelb GRADE
Pacienii cu boal cardiac pot participa la programe
de autongrijire pentru a crete sau menine contientizarea necesitii managementului factorilor de
IIa
B
Puternic
risc, pentru a-i menine condiia fizic sau pentru a-i
autogestiona tratamentul cu anticoagulante orale.
Refc
553
Clasa de recomandri
Nivelul de eviden
c
Referine
a
b
n multe ri, fundaiile care se ocup de sntatea

inimii (care fac parte i din EHN (European Heart Network)), susin programele de auto-ngrijire ale pacienilor cu probleme cardiace care i oraganizeaz propriile grupuri de auto-ngrijire. Majoritatea acestor programe sunt organizate de pacienii cu boli ale arterelor
coronare, indiferent dac au istoric de infarct miocardic, PCI, CABG sau insuficien cardiac congestiv.
Informaiile despre importana tratamentului orientat
n funcie de ghidurile n vigoare sunt eseniale pentru acesti pacieni cu scopul de a menine un tratament
preventiv optim, care are tendina de a fi abandonat n
primele 6 luni de la externare dup infarct miocardic,
PCI sau CABG250. edinele regulate de exerciii, la intervale de o dat pe sptamn sau o data la dou sptmni sub ndrumarea unui fizioterapeut, cu sau fr
supravegherea unui medic, ajut la ntelegerea importanei meninerii condiiei fizice. Pe de alt parte, apariia anginei progresive la niveluri ale exerciiului fizic
mai mare dect efortul de zi cu zi, poate fi un semnal de
alarm precoce c este necesar un consult cardiologic.
n grupurile de auto-ngrijire ale pacienilor cu insuficien cardiac congestiv, accentul se pune pe: controlul greutii cu ajutorul diureticelor; un nivel sczut
de exerciiu fizic, inclusiv exerciii la un anumit interval
de timp; inta este de a menine rezistena muscular
prin exerciii individuale de for i de rezisten a fiecrei grupe de muchi n parte, pentru a evita suprasolicitarea organismului. Toate aceste activiti pot fi
oferite ntr-un program structurat de reabilitare cardiac205.
Pacienii cu FA sau cu proteze valvulare mecanice,
care au nevoie de anticoagulare oral pe toat durata
vieii, pot fi instruii despre principiile de baz ale aces
tui tratament; ei pot de asemenea s nvee cum s determine (acas) INR-ul sptmnal i cum s i dozeze
medicaia anticoagulant pentru a menine valoarea
INR-ului n limitele recomandate i pentru a preveni
posibilele hemoragii sau evenimente tromboembolice.
Dei nu a existat nici o diferen n ceea ce privete endpointurile severe, auto-testarea ofer o mai mare independen pacientului i duce la o calitate mai bun
a vieii553. n plus, dup protezarea valvular, pacienii
se pot confrunta cu probleme cum sunt intervenii chirurgicale noncardiace, cum ar fi operaia de prostat,
protezarea de old sau de genunchi, extirparea tumorilor, extrageri dentare sau alte intervenii chirurgicale
care necesit un management sofisticat a anticoagulrii
perioperatorii, la fel ca i profilaxia endocarditei bacteriene.
Ziarele dedicate pacienilor, de obicei publicate de
fundaiile pentru sntatea inimii, pot menine contientizarea pacienilor despre necesitatea tratamentului
optim prin publicaiile despre importana modificrii
stilului de via pentru controlul factorilor de risc sau
mbuntirea strii de sntate prin metode cum ar fi:
meninerea statusului de nefumtor, creterea intensitii activitii fizice regulate i urmarea unei diete cu
specific mediteranean554. De asemenea, sunt discutate
noile descoperiri n ceea ce privete ngrijirea pacientului sau efectele secundare ale unor medicamente intens
folosite cum ar fi statinele, antiagregantele plachetare
sau amiodarona. Scopul programelor de auto-ngrijire
este de a face pacientul mai responsabil n ceea ce privete boala i de a-l educa. Programele de auto-ngrijire
fac parte dintr-o reea social, care servete ca o platform pentru ajutorul reciproc i pentru comunicarea
dintre pacienii cu aceeai boal. Aceste programe pot
mbunti i facilita managemnetul medical i pot mbunti calitatea vieii pacienilor care se ajuta reciproc pentru a controla zi de zi boala.
Grupurile de auto-ngrijire cresc independena
pacienilor i mbuntesc calitatea vieii.
Lacune rmase
Nu exist studii randomizate care s evalueze
efectul grupurilor de auto-ngrijire asupra endpointurilor cardiovasculare severe.


Vol. 24, No. 4, 2014
5.5 Programe care se bazeaz pe serviciile oferite

n spitale
Recomandri n ceea ce privete programele din spitale
Recomandri
Clasaa Nivelb GRADE
Toi pacienii cu boal cardiovascular trebuie externai
din spital cu recomandri clare de tratament conform
I
B
Puternic
ghidurilor, pentru a minimiza riscul de evenimente
adverse.
a
b
c
Refc
250,
555
Clasa de recomandri
Nivelul de eviden
Referine
5.5.1 Necesitatea recomandrilor bazate pe dovezi

la externare pentru un tratament optim
Ghidurile pentru managementul bolii dup un eveniment cardiovascular recomand modaliti de tratament pentru minimizarea riscului de evenimente cardiovasculare ulterioare. Totui, ntr-un studiu observaional pe 5353 de pacieni cu infarct miocardic, doar
aproximativ jumtate din toi pacienii au fost externai
cu terapie optim conform ghidurilor555.
Procentul pacienilor externai cu terapie optim
poate varia n funcie de diagnostic, de vrst (btrni
vs. tineri), de sex (brbai vs. femei), de tipul de intervenie suferit sau de instituia n care au fost internai556; pacienii externai fr un tratament optim au
un prognostic mai prost la un an555. n programul naional al AHA - `Get with the Guidelines`- a fost inclus medicaia la externare cu un impact asupra prognosticului, incluznd IECA, aspirina, beta-blocantele
i medicamentele hipolipemiante, ca i sfaturi pentru
renunarea la fumat i consiliere. Compliana strict la
tratament (100%) s-a ntlnit cel la mai frecvent la pacienii post PCI (71,5%), urmat de pacienii post CABG
(65,1%), i apoi pacienii fr intervenii (62,1%). Analiza multivariant ajustat n funcie de 14 variabile
clinice, a confirmat faptul c: compliana a fost semnificativ statistic mai mare la pacienii post PCI fa de
cei post CABG, i a fost cea mai mic la pacienii fr
intervenii556. Noile ghiduri ESC ofer o list de msuri
necesare la externarea din spital pentru a asigura faptul
c modificarea intens a factorilor de risc i schimbarea stilului de via sunt implementate la toi pacienii
diagnosticai cu SCA, inclusiv recomandarea pentru
nscrierea ntr-un program de prevenie i reabilitare
cardiovascular557.
cretere semnificativ a complianei la externare n ceea

ce privete: administrarea aspirinei, a inhibitorilor enzimei de conversie a angiotensinei, a medicamentelor
hipolipemiente, consiliere pentru renunarea la fumat
i pentru respectarea dietei559.
ntr-un studiu naional randomizat desfurat n 458
de spitale, un program de mbuntire a calitii, de
intensitate sczut, la pacienii post operaie de bypass,
a inclus o list de msuri care trebuie respectate, materiale pentru implicarea activ i pentru educarea pacientului, care subliniaz importana medicamentelor
pentru prevenia secundar i necesitatea schimbrii
modului de via. S-a observant o cretere semnificativ a ratei de prevenie secundar optimal, cu o aderen mai bun la indicaii la toate subgrupurile de pacieni, n special la femei i la vrstnici; lipsurile care
existau n ceea ce privete tratamentul au fost aproape
n totalitate eliminate, i s-au observant mbuntiri n
folosirea medicamentelor hipolipemiante, a inhibitorilor enzimei de conversie a angiotensinei i a consilierii
pentru renunarea la fumat. n ultimii doi ani a existat
o cretere continu a aderenei medicilor la ghiduri n
ceea ce privete recomnadrile la externare560.
Programe structurate pentru implementarea ghidurilor ar trebui luate n considerare cu scopul de a obine
cel mai mare procentaj posibil de pacieni crora li se
prescrie un tratament n conformitate cu aceste ghiduri, condiie necesar pentru meninerea complianei
pe termen lung la un tratament conform ghidurilor.
Introducerea programelor de mbuntire a calitii duce la mbuntirea recomandrilor la externare.
Lacunele rmase
Inc lipsesc dovezile c eforturile pentru administrarea unui tratament optim la externarea din
spital duc la o mai bun meninere pe termen
lung a msurilor de prevenie secundar i la o
reducere mai mare a evenimentelor cardiovasculare.
Interveniile auxiliare la anumite intervale pot s
fie de asemenea necesare.
5.5.2 Programele de mbuntire sistematic a

calitii serviciilor medicale sunt eseniale
Introducerea unei iniiative intensive, educaionale,
de mbuntire a calitii, bazat pe ghidurile de prevenie secundar ale ACC/AHA din 2001558, a dus la o


Vol. 24, No. 4, 2014
5.6. Programe n spital: centre de prevenie

specializate
Recomandri n ceea ce privete centrele specializate
Recomandri
Clasaa Nivelb GRADE
Toi pacienii care necesit internare sau intervenie
invaziv dup un eveniment ischemic acut ar trebui
s fie inclui ntr-un program de recuperare cardiac
IIa
B
Puternic
pentru mbuntirea prognosticului prin modificarea
stilului de via i creterea aderenei la tratament.
a
Clasa de recomandri
b
Nivelul de eviden
c
Referine
Refc
205,
250
Dup un eveniment cardiovascular, aderena pe termen lung la medicaia prescris are o importan similar cu mbuntirea stilului de via n scopul reducerii riscului de evenimente ischemice recurente. In
studiile randomizate cu un regim terapeutic structurat
i cu monitorizare frecvent dup un SCA, compliana a fost mai mare i rata de evenimente adverse mai
mic561.
5.6.1. Centrele de recuperare cardiac ajut la
mbuntirea stilului de via
n mod obinuit, compliana la recomandrile legate
de modificarea stilului de via i la regimurile terapeutice ncepe s scad la 6 luni de la externarea din spital.
Aderena la modificrile comportamentale (diet, exerciii, i renunarea la fumat) dup un SCA s-a asociat
cu un risc semnificativ mai mic de evenimente cardiovasculare recurente n comparaie cu non-aderena250.
Recuperarea cardiac dup evenimnete cardiace sau
intervenii n centre specializate ajut la meninerea
pe termen lung a aderenei la tratament prin educarea
pacientului i prin sublinierea repetat a importanei
meninerii tratamentului prescris i a recomandrilor
n ceea ce privete stilul de via.
5.6.2 Recuperarea cardiac este cost-eficient
Recuperarea cardiac este considerat o intervenie cost-eficient dup un eveniment coronarian acut;
mbuntete prognosticul prin reducerea spitalizrilor recurente i prin scderea costurilor sistemului de
sntate, n timp de realizeaz i prelungirea vieii562.
Recuperarea cardiac dup un eveniment cardiovascular este o recomandare de Clas I a ESC, AHA i a American College of Cardiology139,205,563,564.
ntruct componentele de baz i obiectivele recuperrii cardiace sunt standardizate i publicate ntr-un
document205, structura i tipul unitilor de recuperare cardiac variaz n diferite ri. Tradiiile sistemului de sntate i considerentele legate de costuri joac
roluri importante. Centrele de recuperare cardiac de
tip rezidenial, n care pacientul este scos din mediul

su obinuit i triete ntr-un mediu idealizat timp de
2-3 sptmni pentru a se familiariza cu medicamentele necesare i se obinuiete cu un stil de via sntos,
sunt o opiune n mai multe ri europene, i, de obicei,
sunt urmate de sesiuni de instruire ambulatorie, acas.
Alte ri sunt n favoarea unitilor de recuperare ambulatorii unde pacienii particip o dat sau de dou ori
pe sptmn la sesiuni de recuperare pe o perioad de
cteva luni i ncearc s implementeze recomandrile legate de schimbarea stilului de via n mediul su
obinuit, inclusiv dup reluarea activitii.
Un studiu multicentric randomizat, desfurat pe o
perioad de 3 ani, a fost efectuat pentru a compara un
program de recuperare pe termen lung, susinut, cuprinznd intervenii multifactoriale educaionale i
pentru modificarea stilului de via, coordonat de un
cardiolog versus ngrijirea ntr-un program de recuperare standard (rezidenial sau ambulator) la pacienii
dup un infarct miocardic din centre de recuperare.
Intervenia s-a dovedit eficient n ameliorarea factorilor de risc i n creterea aderenei la tratament de-a
lungul timpului, cu o mbuntire semnificativ a stilului de via (de exemplu: exerciii fizice, diet, stres
psiho-social i greutate corporal). Obiective clinice
au fost de asemenea reduse prin intervenia intensiv:
mortalitatea cardiovascular, infarctul miocardic nonfatal, i accidentul vascular cerebral cu 33% (p = 0,02),
i moartea de cauz cardiac plus infarctul miocardic
non-fatal cu 36% (p = 0,02), accidentul vascular cerebral cu 32%, iar mortalitatea total cu 21% (p = nesemnificativ)565.
5.6.3 Provocri pentru recuperarea cardiac:
sexul feminin i comorbiditile
Rezultatele care sunt ateptate n urma tutror interveniilor de recuperare cardiac sunt mbuntirea
strii clinice i controlul simptomelor, reducerea riscul
cardiovascular global , creterea aderenei la indicaiile
farmacologice, i un profil comportamental mai bun,
toate acestea conducnd la o mbunatire a calitii
vieii i la ameliorarea prognosticului. Cu toate acestea,
eforturile ndelungate dincolo de faza de nceput sunt
necesare pentru a menine compliana la tratament i
la modificarea stilului de via.
O provocare deosebit pentru programele de recuperare sunt pacienii vrstnici i femeile205,566 i pacienii cu comorbiditi specifice, cum ar fi atacul ischemic
tranzitor sau accidentul vascular cerebral, boala pulmonar cronic obstructiv i insuficiena renal cronic.
O nou provocare n toat Europa este de a satisface

Vol. 24, No. 4, 2014
nevoile minoritilor etnice cu valori culturale uneori

diferite, i, uneori, cu lipsa de vorbire fluent n limba
rii de reedin205. Succesul eforturilor de recuperare
i de prevenie secundar depind de un nivel ridicat de
ngrijire individual i de sprijin, cu o evaluare clinic
atent mai mult dect funcia cardiovascular, inclusiv
evaluare psihosocial i evaluarea comorbiditilor.
5.6.4 Sesiunile repetate mbuntesc compliana
Din rezultatele unui studiu mare observaional s-a
sugerat c numrul de sesiuni de recuperare (de exemplu, durata i intensitatea interveniei i motivaia participantului) s-a corelat cu mbuntirea prognosticului67. Aceasta a fost susinut de rezultatele studiului
Global Secondary Prevention Strategies to Limit Event
Recurrence After MI (GOSPEL) (Strategii de Prevenie
Secundar pentru a limita Recurena Evenimentelor
dup IM ) unde o intervenie pe termen lung a fost mai
eficace dect una pe termen scurt565.
Faptul dac recuperarea se efectueaz ntr-un cadru
ambulator sau ntr-un centru rezidenial este, probabil, de o importanv mai redus; durata programului,
nivelul de educaie i motivaia pacientului sunt de
asemenea importante pentru prognosticul pe termen
lung205.
Rata de participare la un program de recuperare
dup un eveniment cardiovascular este mult mai mic
dect ar fi de dorit: doar ~30% dintre pacienii eligibili
din Europa particip la un astfel de program, cu variaii
considerabile ntre ri5. Dei recuperarea cardiac este
cost-eficien din punctul de vedere al societii, va fi o
provocare major n viitor pentru a mbunti aceast
rat sczut de participare n ntreaga Europ.
Recuperarea cardiac este cost-eficient n reducerea riscului de evenimente cardiovasculare.
Lacune rmase
Durata optim a unui program de recuperare
cardiac rmne necunoscut.
5.7 Programele organizaiilor non-guvernamentale
Mesajul-cheie
Organizaiile non-guvernamentale sunt parteneri importani pentru angajaii sistemului de sntate n promovarea cardiologiei preventive.
EHN este o alian a fundaiilor inimii cu sediul la
Bruxelles i cu organizaii non-guvernamentale n ntreaga Europ, cu organizaii membre n 26 de ri.
EHN joac un rol important n prevenirea - n special

a bolilor cardiace i a accidentului vascular cerebral prin susinere, crearea de reele, educaie, i sprijinirea
pacientilor, astfel nct aceste afeciuni s nu mai fie
cauza major de deces prematur i de dizabiliti n ntreaga Europ568.
Pentru a-i atinge scopul, EHN se dedic pentru a
influena responsabilii politici europeni europeni n favoarea unui stil de via sntos; crearea i cultivarea
legturilor dintre organizaiile implicate n promovarea sntii inimii i n prevenirea BCV; strngerea i
distribuirea de informaii relevante pentru promovarea
sntii inimii; i consolidarea relaiilor ntre membri.
EHN funcioneaz prin grupuri de experi, cu accent
pe: nutriie pentru sntatea cardiovascular, politica
legat de tutun i descurajarea fumatului, medicina
muncii i factorii psihosociali, i activitatea fizic ca o
parte component a vieii de zi cu zi.
EHN faciliteaz crearea de reele n rndul organizaiilor sale membre, care lucreaz n mod activ pentru a sprijini pacienii cu boli cardiace i pacienii cu
accident vascular cerebral. Aproximativ jumtate din
membrii organizaiilor se ncadreaz n aceast categorie. Organizaiile pacienilor cu boli cardiovasculare
pot oferi membrilor lor posibilitatea de a obine sprijin
de la colegii lor. Ele informeaz pacientul sub form de
brouri i materiale publicate pe internet i promoveaz
recuperarea cardiac.
5.8 Aciunea de la nivel politic european
Mesajul-cheie
Carta European Heart Health marcheaz nceputul unei noi ere de angajament politic n cardiologia preventiv.
n 2002, conducerea ESC a marcat implicarea sa viitoare n politicile de sanatate prin realizarea unei strategii pentru statele membre de a reduce decesele prin
BCV cu 40%. Era clar c pentru profesionitii din domeniul medical, pentru a avea un impact asupra factorului de decizie politic de la nivel UE i naional, ar
fi necesar s se constituiasc aliane puternice cu alte
organizaii non-guvernamentale implicate n sntate,
n primul rnd EHN, dar, de asemenea, cu autoritile
locale responsabile de sntate i cu UE. Lucrarea a fost
iniiat prin furnizarea de expertize exacte i statistici
alarmante cu privire la povara uria a BCV n Europa,
i a dus la o cerin de a aciona n privina BCV din
partea statelor membre i a Comisiei Europene.
Aceast iniiativ a fost urmat de un parteneriat
cu preedenia irlandez n 2004. S-a ajuns la concluzia c cele mai multe cazuri de BCV pot fi prevenite

prin modificarea stilului de via i utilizarea adecvat a

medicamentelor deja existente. Concluziile Consiliului
UE privind BCV a constituit prima declaraie politic
la nivelul UE, prin care se recunotea necesitatea de a
mbuntii sntatea cardiovascular n Europa. Colaborrile cu succes cu preedeniile Luxemburg, Austria,
i Portugalia au deschis calea, mpreun cu EHN, pentru a crea o cart a European Heart Health (Carta european a sntii inimii). Aceast cart a fost lansat n
iunie 2007 la Parlamentul European, i a fost aprobat
de ctre Comisia European i OMS Europa. Aceast
evoluie a deschis calea pentru o rezoluie a Parlamentului European privind msurile de combatere a bolilor
cardiovasculare, cel mai puternic acord politic pn n
prezent cu privire la necesitatea de prevenire a BCV n
Europa568. Carta subliniaz intele i obiectivele universale pentru prevenia BCV i ofer aciunile care trebuiesc ntreprinse n scopul de a atinge aceste obiective. A
fost tradus n 26 de limbi i adoptat n mod oficial de
ctre 30 de state membre UE i de alte ri Europene6.
n perioada urmtoare, ESC s-a gndit c o combinare a eforturilor cu alte boli ar putea crete influena.
Pentru a reui a trebuit depit provocarea politic de
a reuni tiina din diferite domenii de a transmite un
singur mesaj prin care s beneficieze toate bolile reprezentate de grup. n iunie 2009, ESC a invitat organizaiile medicale reprezentnd diabetul, bolile respiratorii
i cancerul pentru a reflecta asupra factorilor comuni
determinani ai sntii, pentru identificarea zonelor
cu dovezi suficiente pentru a susine recomandrile, i
pentru discutarea viitoarelor colaborri. Au fost identificai patru factori de risc ca prezentnd suficiente
elemente comune pentru a justifica aciunile comune:
fumatul, alimentaia, consumul de alcool i lipsa activitii fizice. Astfel, a fost nfiinat Chronic Disease
Alliance (Aliana European a Bolilor Cronice). Aceast alian cuprinde n prezent 10 organizaii europene
nonprofit reprezentnd >100 000 de profesioniti din
sistemele de sntate.
Se adreseaz tuturor bolilor cronice majore netransmisibile, inclusiv bolile cardiace, accidentul vascular
cerebral, hipertensiunea arterial, diabetul zaharat,
boala de rinichi, cancerul, bolile respiratorii, i bolile
hepatice172. Aliana, care va facilita controlul factorilor de risc la nivel populaional , are potenialul unui
impact mare asupra sntii publice i a economiilor
sistemului de sntate.
n concluzie, autorii ghidurilor sper c acest document va susine un parteneriat real ntre politicieni,
medici, personal medical auxiliar, asociaii stiintifice,
fundaiile inimii, organizaii de voluntari, i asociaii

Vol. 24, No. 4, 2014
le de consumatori pentru a promova att sntatea la

nivel populaional ct i prevenia primar i prevenia
cardiovascular, utiliznd spectrul complet de dovezi
medicale din studiile experimentale i din observaiile
populaionale.
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Labarthe DR, Limacher MC, Lloyd-Jones DM, Mora S, Pearson TA,
Radford MJ, Smetana GW, Spertus JA, Swegler EW. AHA/ACCF
[corrected] 2009 performance measures for primary prevention of
cardiovascular disease in adults: a report of the American College of
Cardiology Foundation/American Heart Association task force on
performance measures (writing committee to develop performance
measures for primary prevention of cardiovascular disease): developed in collaboration with the American Academy of Family Physicians; American Association of Cardiovascular and Pulmonary Rehabilitation; and Preventive Cardiovascular Nurses Association: endorsed
by the American College of Preventive Medicine, American College
of Sports Medicine, and Society for Womens Health Research. Circulation 2009;120:12961336.
Matchar DB, Jacobson A, Dolor R, Edson R, Uyeda L, Phibbs CS,
Vertrees JE, Shih MC, Holodniy M, Lavori P. Effect of home testing
of international normalized ratio on clinical events. N Engl J Med
2010;363:16081620.
Folsom AR, Yatsuya H, Nettleton JA, Lutsey PL, Cushman M, Rosamond WD. Community prevalence of ideal cardiovascular health, by
the American Heart Association definition, and relationship with cardiovascular disease incidence.J Am Coll Cardiol 2011;57:16901696.
Bramlage P, Messer C, Bitterlich N, Pohlmann C, Cuneo A, Stammwitz
E, Tebbenjohanns J, Gohlke H, Senges J, Tebbe U. The effect of optimal medical therapy on 1-year mortality after acute myocardial infarction. Heart 2010;96: 604609.
Hiratzka LF, Eagle KA, Liang L, Fonarow GC, LaBresh KA, Peterson
ED. Atherosclerosis secondary prevention performance measures
after coronary bypass graft surgery compared with percutaneous catheter intervention and nonintervention patients in the Get With the
Guidelines database. Circulation 2007;116:I2071212.
Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, Caso
P, Dudek D, Gielen S, Huber K, Ohman M, Petrie MC, Sonntag F, Uva
MS, Storey RF, Wijns W, Zahger D, Bax JJ, Auricchio A, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C,
Hasdai D, Hoes A, Knuuti J, Kolh P, McDonagh T, Moulin C, Poldermans D, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Torbicki
A, Vahanian A, Windecker S, Achenbach S, Badimon L, Bertrand M,
Botker HE, Collet JP, Crea F, Danchin N, Falk E, Goudevenos J, Gulba D, Hambrecht R, Herrmann J, Kastrati A, Kjeldsen K, Kristensen
SD, Lancellotti P, Mehilli J, Merkely B, Montalescot G, Neumann FJ,
Neyses L, Perk J, Roffi M, Romeo F, Ruda M, Swahn E, Valgimigli
M, Vrints CJ, Widimsky P. ESC Guidelines for the management of
acute coronary syndromes in patients presenting without persistent
ST-segment elevation: The Task Force for the management of acute
coronary syndromes (ACS) in patients presenting without persistent
ST-segment elevation of the European Society of Cardiology (ESC).
Eur Heart J 2011;32:29993054.
Smith SC Jr, Blair SN, Bonow RO, Brass LM, Cerqueira MD, Dracup K, Fuster V, Gotto A, Grundy SM, Miller NH, Jacobs A, Jones
D, Krauss RM, Mosca L, Ockene I, Pasternak RC, Pearson T, Pfeffer
MA, Starke RD, Taubert KA. AHA/ACC Scientific Statement: AHA/
ACC guidelines for preventing heart attack and death in patients with

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healthcare professionals from the American Heart Association and
the American College of Cardiology. Circulation 2001;104: 1577
1579.
Yam FK, Akers WS, Ferraris VA, Smith K, Ramaiah C, Camp P, Flynn
JD. Interventions to improve guideline compliance following coronary artery bypass grafting. Surgery 2006;140:541547; discussion
547552.
Williams JB, Delong ER, Peterson ED, Dokholyan RS, Ou FS, Ferguson TB Jr. Secondary prevention after coronary artery bypass graft
surgery: findings of a national randomized controlled trial and sustained society-led incorporation into practice. Circulation 2011;123:39
45.
Rauch B, Schiele R, Schneider S, Diller F, Victor N, Gohlke H, Gottwik M, Steinbeck G, Del Castillo U, Sack R, Worth H, Katus H, Spitzer W, Sabin G, Senges J. OMEGA, a randomized, placebo-controlled
trial to test the effect of highly purified omega-3 fatty acids on top of
modern guideline-adjusted therapy after myocardial infarction. Circulation 2010;122:21522159.
Jolliffe JA, Rees K, Taylor RS, Thompson D, Oldridge N, Ebrahim S.
Exercisebased rehabilitation for coronary heart disease. Cochrane
Database Syst Rev 2001;1:CD001800.
Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand
M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany
CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr. ACC/AHA guidelines for the management of patients with ST-elevation myocardial
infarctionexecutive summary. A report of the American College
of Cardiology/American Heart Association Task Force on Practice
Guidelines (Writing Committee to revise the 1999 guidelines for the
management of patients with acute myocardial infarction). J Am Coll
Cardiol 2004;44:671719.
Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine
CJ, Schaeffer JW, Smith EE 3rd, Steward DE, Theroux P, Gibbons RJ,
Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK,
Smith SC Jr. ACC/AHA 2002 guideline update for the management of
patients with unstable angina and non-ST segment elevation myocardial infarctionsummary article: a report of the American College of
Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable
Angina). J Am Coll Cardiol 2002;40:13661374.
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Ceci V, Chieffo C, Gattone M, Griffo R, Schweiger C, Tavazzi L, Urbinati S, Valagussa F, Vanuzzo D. Global secondary prevention strategies to limit event recurrence after myocardial infarction: results of
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168:21942204.
Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ,
Ganiats TG, Gomes AS, Gornik HL, Gracia C, Gulati M, Haan CK,
Judelson DR, Keenan N, Kelepouris E, Michos ED, Newby LK, Oparil
S, Ouyang P, Oz MC, Petitti D, Pinn VW, Redberg RF, Scott R, Sherif
K, Smith SC Jr, Sopko G, Steinhorn RH, Stone NJ, Taubert KA, Todd
BA, Urbina E, Wenger NK. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. J Am Coll Cardiol
2007;49:12301250.
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between cardiac rehabilitation and long-term risks of death and myocardial infarction among elderly Medicare beneficiaries. Circulation
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disease. 2007. Procedure: 2007/2601(RSP). http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+TA+P6-TA-20070346+0+DOC+XML+V0//EN&language=EN.
NATIONAL AND INTERNATIONAL CARDIOLOGY AGENDA 2015

EVENIMENTE SRC 2015
LUNA
February
March
APRIL
MAY
JUNE
SEPTEMBER
OCTOBER
DENUMIREA MANIFESTRII
ANATOMY IN HEART FAILURE MODUL I - AORTA
Directori de curs: Dr. O. Chioncel
CAZURI CLINICE DIFICILE IN INSUFICIENA CARDIAC
Directori de curs: Prof. Dr. C. Macarie, Prof. Dr. D. Vinereanu, Dr. O. Chioncel
REDRISC (REDucerea RISCului Rezidual)
Directori de curs: Prof. Dr. D. Vinereanu, Prof. Dr. Ctlina Arsenescu Georgescu,
Prof. Dr. G.A. Dan, Prof. Dr. F. Mitu
HIPERTENSIUNEA ARTERIAL DE LA TEORIE LA PRACTIC, DE LA
GHIDURI LA PACIENI
Directori de curs: Prof. Dr. D. Barto, Dr. E. Bdil
IMAGISTICA N CARDIOMIOPATII
Directori de curs: Dr. Ruxandra Jurcu, Conf. Dr. Dr. B.A. Popescu
ACTUALITI N ARITMOLOGIE (ARCA 4)
Directori de curs: Dr. A. Deutsch, Dr. M. Grecu
ELOGIU
Directori de curs: Prof. Dr. E. Apetrei, Dr. R. Ciudin
INIMA I SPORTUL (curs de cardiologie sportiv)
Directori de curs: Prof. Dr. M.I. Popescu, Prof. Dr. D. Zdrenghea
CARDIOCOAG
Directori de curs: Prof. Dr. D. Vinereanu, Prof. Dr. F. Mitu, Prof. Dr. D. Lighezan
URGENE CARDIOVASCULARE N SITUAII SPECIALE
Directori de curs: Conf. Dr. D. nt, Dr. V. Chioncel, Dr. G. Tatu Chioiu
REDRISC (REDucerea RISCului Rezidual)
Directori de curs: Prof. Dr. D.Vinereanu, Prof. Dr. Ctlina Arsenescu Georgescu,
Prof. Dr. G.A. Dan, Prof. Dr. F. Mitu
REVASCULARIZARE N STEMI/nonSTEMI
Directori de curs: Dr. . Mo, Dr. D. Deleanu, Dr. I. Nedelciuc
CONFERINA NAIONAL DE ATEROTROMBOZ
Moderatori: Prof. Dr. E. Apetrei, Prof. Dr. C. Popa
REVASCULARIZARE MIOCARDIC DE LA GHIDURI LA PRACTIC
Directori de curs: Dr. D. Deleanu, Prof. Dr. L. Petrescu, Dr. A. Mereu
CONFERINA NAIONAL A GRUPURILOR DE LUCRU
SIMPOZIONUL INTERNAIONAL DE CARDIOMIOPATIE
HIPERTROFIC
HIPERTENSIUNEA ARTERIAL DE LA TEORIE LA PRACTIC, DE LA
GHIDURI LA PACIENI
Directori de curs: Prof. Dr. D. Barto, Dr. E. Bdil
SIMPOZION ANUAL DE ACTUALITI N CARDIOLOGIA
INTERVENIONAL
Directori de curs: Dr. . Mo, Dr. D. Deleanu, Dr. L. Zarma
ELOGIU
Directori de curs: Prof. Dr. E. Apetrei, Dr. R. Ciudin
EXPERT MEETING CARDIODIAB
CONGRESUL NAIONAL DE CARDIOLOGIE
REVASCULARIZARE N STEMI/nonSTEMI
Directori de curs: Dr. . Mo, Dr. D. Deleanu, Dr. V. Popa
INIMA I SPORTUL (curs de cardiologie sportiv)

Directori de curs: Prof. Dr. M.I. Popescu, Prof. Dr. D. Zdrenghea
DATA
LOCAIA
27 februarie
Bucureti
6 martie
Sibiu
6 martie
Bucureti
13 martie
Caransebe
13 martie
Bucureti
20 martie
Sibiu
20 martie
Bucureti
20 martie
Oradea
27 martie
Craiova
27 martie
Constana
28 martie
Cluj Napoca
1 aprilie
Iai
24 aprilie
Bucureti
24 aprilie
Iai
7-9 mai
Sibiu
9 mai
Sibiu
5 iunie
Piatra Neam
12 iunie
Bucureti sau
Chiinu
19 iunie
Craiova
25-27 iunie
17-19
septembrie
Poiana Braov
1 octombrie
Oradea
9 octombrie
Brila
Sinaia

Vol. 24, No. 4, 2014
Agenda
IMAGISTICA N CARDIOMIOPATII
Directori de curs: Dr. Ruxandra Jurcu, Conf. Dr. B.A. Popescu
ABORDAREA DIAGNOSTIC I TERAPEUTIC MODERN A

PATOLOGIEI CARDIOVASCULARE PEDIATRICE I NEONATALE
16 octombrie
Iai
22 octombrie
Timioara
23 octombrie
Trgu Mure
23 octombrie
Iai
30 octombrie
Oradea
29-31
octombrie
Iai
6 noiembrie
Timioara
6 noiembrie
Craiova
20 noiembrie
Craiova
DATE
PLACE
January 14-17
Paris, France
January 18-20
Tel Aviv, Israel
Directori de curs: Conf. Dr. Gabriela Doro, Dr. Anca Popoiu
CARDIOCOAG
OCTOBER
Directori de curs: Prof. Dr. D. Vinereanu, Prof. Dr. F. Mitu, Prof. Dr. D. Lighezan
ANATOMY IN HEART FAILURE MODUL I - AORTA

Directori de curs: Dr. O. Chioncel
REVASCULARIZARE MIOCARDIC DE LA GHIDURI LA

PRACTIC
Directori de curs: Dr. D. Deleanu, Prof. Dr. L. Petrescu, Dr. A. Mereu
ZILELE CARDIOLOGICE Prof. Dr. GEORGE M.I. GEORGESCU

CAZURI CLINICE DIFICILE IN INSUFICIENA CARDIAC
Directori de curs: Prof. Dr. C. Macarie, Prof. Dr. D. Vinereanu, Dr. O. Chioncel
NOVEMBER
URGENE CARDIOVASCULARE N SITUAII SPECIALE

Directori de curs: Conf. Dr. D.nt, Dr. V.Chioncel, Dr. G.Tatu Chioiu
ACTUALITI N ARITMOLOGIE (ARCA 4)

Directori de curs: Dr. A. Deutsch, Dr. M. Grecu
CARDIOLOGY EVENTS IN THE WORLD

MONTH
NAME OF THE EVENT

XXV European Days Annual Meeting of the French Society of
Cardiology
www.sfcardio.fr
January
The 9th International Conference Acute Cardiac Care 2015

www.isas.co.il, www.acute-cardiac-care.com
CardioRhythm 2015
http://www.cardiorhythm.com/?hit=wca
CardioRhythm 2015
http://www.cardiorhythm.com/?hit=wca
SCMR/EuroCMR 2015, Joint Scientific Sessions

http://www.escardio.org/congresses/eurocmr-2015/Pages/welcome.aspx
January 30 February 1
January 30 February 1
February
JIM 2015 (Joint Interventional Meeting)

www.jim-vascular.com
CRT 2015, Cardiovascular Research Technolologies

www.crtonline.org
Resistant Hypertension Course. 3rd Edition

http://www.escardio.org/communities/EAPCI/congress-meetings/Pages/resistanthypertension-course.aspx?hit=wca
Stent for Life Forum

www.stentforlife.com
ACCs Annual Scientific Session 2015

www.accscientificsession.org
Clinical Workshop on Cardiac MR stress Imaging

March
http://cvti.org.uk/?hit=wca
The 6th International Conference on Fixed Combination in the

treatment of Hypertension, Dyslipidemia and Diabetes Mellitus
www.fixedcombination.com
Hong Kong
February 4-7
Nice, France
February 8-12
Davos,
Switzerland
Cardiology Update 2015, an ESC Update Programme

http://www.escardio.org/education/live-events/courses/cardiology-update/Pages/
Programme.aspx?hit=wca
Hong Kong
February
12-14
February
21-24
Washington,
USA
February
26-28
Berlin,
Germany
February
27-28
Prague, Czech
Republic
San Diego, CA,
USA
March 14-16
Rome, Italia
March 20-21
London, UK
March 26-29
Berlin,
Germany

Vol. 24, No. 4, 2014
March
The 18th Prague Workshop on Catheter Ablation

http://www.ablationworkshop.cz
The 4th CardioSleep Congress. A focus on Heart Failure & Sleep Apnea
http://www.cardiosleep.org/about-us/?hit=wca
Atrial Fibrillation - from atrial extrasystoles to atrial cardiomyopathy

APRIL
https://akkonferens.slu.se/afsymposium2015/?hit=wca
Cardiac MRI & CT, Clinical Update 2015

http://cardiacmri-ct.medconvet.at
Agenda
March 29-31
Prague, Czech
Republic
April 10-11
Paris, France
April 16-1
Stockholm,
Sweden
April 16-18
Cannes, France
April 18-20
Catania, Italy
May 3-5
Madrid, Spain
May 8-9
Dubrovnik,
Croatia
May 13-16
Boston, MA,
USA
May 14-16
Lisbon,
Portugal
May 19-22
Paris, France
May 20-23
Prague, Czech
Republic
May 23-26
Sevilla, Spain
May 24-27
Amsterdam,
Holland
May 27-29
Paris, France
May 29-30
Marsilia,
France
June 4-6
Munich,
Germany
June 4-6
Lyon, France
June 7-9
Nice, France
June 21-24
Milan, Italy
June 22-26
St. Wolfgang,
Austria
June 24
Frankfurt,
Germany
June 25-27
Frankfurt,
Germany
th
The 7 edition of Mediterranean Cardiology Meeting 2015

http://www.mcmweb.it/en/invitation_letter.php
ICNC12, Nuclear Cardiology and Cardiac CT

http://www.escardio.org/congresses/icnc12/Pages/welcome.aspx?hit=wca, www.
icnc12.org
EuroHeartCare 2015, Annual Congress of the Council on

Cardiovascular Nursing and allied Professions
www.escardio.org/EuroHeartCare
Heart Rhythm 2015, the 36th Annual Scientific Sessions

http://www.heartrhythmsupport.org/exhibits/hrs.html
EuroPrevent 2015
http://www.escardio.org/congresses/europrevent-2015/Pages/welcome.aspx, www.
escardio.org/europrevent
EuroPCR 2015
MAY
www.europcr.com
AEPC 2015, the 49th Annual Meeting of the Association for European
Paediatric and Congenital Cardiology
www.aepc2015.org
HEART FAILURE 2015, 2nd World Congress on Acute Heart Failure

2015
www.escardio.org/HFA
ISA 2015, the 17th International Symposium on Atherosclerosis

www.isa-2015.com
PARIS - ECHO 2015

http://www.paris-echo.com/index.php/fr/?hit=wca
The 8th Rhythm Congress

www.rhythmcongress.com
The 7th Annual European Course on Cardiovascular Magnetic

Resonance
www.cmr-course.de
16th ISCHNE (Congress of the International Society for Holter and

Noninvasive Electrocardiology, ISHNE)
www.ishne2015.org
MEET 2015, Multidisciplinary European Endovascular Therapy

www.meetcongress.com
EHRA EUROPACE CARDIOSTIM 2015

JUNE
www.escardio.org/congresses/ehra-europace-2013/Pages/welcome.aspx,
www.escardio.org/EUROPACE, www.cardiostim.com
Advanced Echocardiography with Illustrative Case Studies

www.cardiology.co.at
ICI 2015, Imaging in Structural, Valvular and Congenital

Interventions
www.csi-imaging.org
CSI 2015 Congenital, Structural, Valvular and Congenital

Interventions
www.csi-congress.org

Vol. 24, No. 4, 2014
Agenda
AUGUST
ESC CONGRESS 2015

www.escardio.org/ESC2015
ESC CONGRESS 2015

www.escardio.org/ESC2015
SEPTEMBER
WSA 2015, XV World Congress on Cardiac Pacing and

Electrophysiology
www.wsa2015.org
3D Echo 360, European edition

www.3dechows.com
Transcatheter Cardiovascular Therapeutics (TCT) 2015

www.tctconference.com, www.tctmd.com
OCTOBER
London, UK
London, UK
September
17-20
Beijing, China
September
25-27
Padua, Italy
October 12-16
San Francisco,
CA, USA
October 16-18
Venice, Italy
November 5-7
Istanbul,
Turkey
November
7-11
Orlando,
Florida, USA
December 2-5
Sevillia, Spain
VeniceArrhythmias 2015. The 14th International Edition

www.venicearrhythmias.org, http://www.escardio.org/_controltemplates/
EscWebSite/www.venicearrhythmias.org?hit=wca
CODHy - The 5th World Congress on Controversies to Consensus in

Diabetes, Obesity and Hypertension
NOVEMBER
August 29 - 2
September
August 29 - 2
September
www.codhy.com
American Heart Association Annual Scientific Sessions 2014

www.scientificsessions.org
EUROECHO & Other Imaging Modalities 2015

DECEMBER
www.euroecho.org, http://www.escardio.org/congresses/euroecho2012/Pages/
welcome.aspx
INSTRUCTIONS FOR AUTHORS

General information
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For publication, articles will be sent electronically, written at double line spacing with Times New Roman 12
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Each manuscript must be accompanied by an authors letter of intent, signed in original by all authors stating
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All authors will sign a statement on conflict of interest and will indicate their contribution in the elaboration of
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Title: On the title page the title of the article should be written in English and Romanian, the full name of the
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authors have already published in the Romanian Journal of Cardiology, the quotation of these publications.
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Vol. 24, No. 4, 2014
Instructions for authors
commendation from the figures). If applicable, the bibliographical source of the table and notice of copyright shall
be specified between brackets.
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THE ROMANIAN SOCIETY OF CARDIOLOGY BOARD

Mihai Gheorghiade - USA

Gian Luigi Nicolosi - Italia

Societatea Romn de Cardiologie

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O. Stiru, L.F. Dorobantu, A. Pasare, S. Bubenek, D. Filipescu, H. Moldovan, V. A. Iliescu

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Ce poate ascunde un pacient oncologic cu dispnee de efort?

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Calendarul manifestrilor tiinifice cardiologice 2015

Instruciuni pentru autori

Romanian Journal of Cardiology | Vol. 24, No. 4, 2014

Acute type A aortic dissection. A single center experience

Emergency Institute for Cadiovascular Diseases Prof. Dr. C. C. Iliescu

Ovidiu Stiru et al.

Romanian Journal of Cardiology

MATERIAL AND METHODS

repair between January 2005 and May 2013. A total of

Ovidiu Stiru et al.

Romanian Journal of Cardiology

and replacement of the ascending aorta. After reaching

Figure 1. Femoral artery cannulation trend over time.

artery (65.95%), immediately followed by right or left

Ovidiu Stiru et al.

Romanian Journal of Cardiology

Figure 2. Axillary artery cannulation trend time.

performed in all cases for tear inspection of the aortic

Mean ventilatory support period

Table 3. Operative patient characteristics

Mortality rate (%)

CPB time (min)

Romanian Journal of Cardiology

Figure 3. Mortality rates over time.