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RR E V I E W

Management
Coronary artery of intracerebral
disease in hemorrhage
women: a review
on prevention, pathophysiology, diagnosis, and
treatment
Ramandeep Sahni
Jesse Weinberger
Abstract: Currently, intracerebral hemorrhage (ICH) has the highest mortality rate of all stroke
subtypes (Counsell et al 1995; Qureshi et al 2005). Hematoma growth is a principal cause of
early neurological deterioration. Prospective and retrospective studies indicate that up to 38%
Department of Neurology, Mount
Sinai School of Medicine, New York, hematoma expansion is noted within three hours of ICH onset and that hematoma volume is an
Leila
NY, USAFernandes Araujo Abstract:predictor
important Despite numerous
of 30-daystudies on women’s
mortality cardiac
(Brott et al 1997;health
Qureshi throughout the This
et al 2005). past decade, the
article will
Alexandre de Matos Soeiro numbercurrent
review of female deaths caused
standard of careby cardiovascular
measures for ICH disease stilland
patients risesnew
andresearch
remains the leading
directed at cause
early
Juliano Lara Fernandes of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular
hemostatic therapy and minimally invasive surgery.
Antônio Eduardo Pesaro disease, and more
Keywords: ICH, specifically coronaryrecombinant
hemostatic therapy, artery diseasefactor
presentations in women,
VII, surgical are different than
management
Carlos V Serrano Jr those in men. In addition, pathology and pathophysiology of the disease present significant
gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the
Heart Institute (InCor), University Intracerebral hemorrhage
female population. The reason for this disparity is all steps for female cardiovascular disease
of São Paulo, School of Medicine,
Brazil
An intracerebral
evaluation, hemorrhage
treatment (ICH)
and prevention account
are not for only 15%
well elucidated; and an ofarea
all strokes
for futurebut it is one
research. of
This
the most
review disabling
brings forms
together of stroke
the most recent (Counsell et al 1995;
studies published in the Qureshi et al 2005).
field of coronary arteryGreater
disease
in women
than and points
one third out new
of patients directions
with for future
intracerebral investigation
hemorrhage on some
(ICH) willofnot
thesurvive
important andissues.
only
Keywords:
twenty coronary
percent artery disease,
of patients women,
will regain risk factors,
functional prevention,(Counsell
independence diagnosis,ettreatment.
al 1995).
This high rate of morbidity and mortality has prompted investigations for new medical
and surgical therapies for intracerebral hemorrhage.
Introduction
Primary ICH develops in the absence of any underlying vascular malformation
Thecoagulopathy.
or first female-specific
Primaryrecommendations for preventive
intracerebral hemorrhage cardiology
is more common were
thanpublished
secondary in
1999 (Mosca et
intracerebral al 1999). Even
hemorrhage. though research
Hypertensive in the treatment
arteriosclerosis andofcerebral
cardiovascular
amyloiddisease
angi-
(CVD) had advanced in many areas, it remains the leading
opathy (CAA) are responsible for 80% of primary hemorrhages (Sutherland cause of death in women
and Auer in
most parts
2006). of the it
At times world.
may Studies
be difficulthavetoshown thatthe
identify 500underlying
thousand womenetiologydiebecause
of CVDpoorly
every
year in the United States, somewhat near one death every
controlled hypertension is often identified in most ICH patients. Patients with CAA- minute (American Heart
Association
related ICH are2003).
moreSuch index
likely exceeds
to be older andnot only the number
the volume of deaths inismen,
of hemorrhage usuallybut⬎ also
30the
cc
next seven causes of death in women combined, and more importantly,
(Ritter et al 2005). Hypertension related ICH is frequently seen in younger patients, coronary artery
disease (CAD)
involving is believed
the basal ganglia,to be
andthethe
major
volumecauseofresponsible for these
blood is usually ⬍ deaths (American
30 cc (Lang et al
2001). However these characteristics are nonspecific and histopathological to
Heart Association 2003). Over a quarter of a million deaths per year are attributed CAD
studies
alone
are in the to
needed United
confirmStates (Merz
a defi et al
nitive 2004). Although
diagnosis of CAA already high, these
or hypertension figuresICH.
related are
expected to rise even more during the next decades, due to an increase
Hypertension causes high pressure within the Circle of Willis resulting in smooth cell of diabetes and
obesity, as well
proliferation as the aging
followed of themuscle
by smooth world population
cell death. (Merz
This may et alexplain
2004). why hypertension
Even though women have a higher frequency of
related ICH are frequently located deep within the basal ganglia, thalamuschest pain/angina than men, the
(Figure 1),
incidence of obstructive CAD in the female population is lower
cerebellum, pons and rarely the neocortex (Campbell and Toach 1981; Sutherland and when compared with
men with
Auer similar
2006). symptoms
In contrast, (Kenedy etamyloid
preferential al 1982; Diamond
depositionet within
al 1983;leptomeningeal
Merz et al 1999).and In
addition, it wouldcortical
intraparenchymal appear vessels
that youngmay women
explain with obstructive
the reason CAD
for large havecial
superfi a worse
lobar
prognosis after acute myocardial infarction (AMI), whereas
hemorrhages with amyloid angiopathy (Auer and Sutherland 2005). It is important older women in similar
circumstances
to identify those often
afflpresent
icted withwithcerebral
larger number
amyloidof comorbidities
angiopathy becausethat adversely
of the influence
high risk
the outcome, when compared to men (Coronado et al 1997).
of recurrent lobar hemorrhage and predisposition for symptomatic hemorrhage Women with acute coronarywith
Correspondence: Ramandeep Sahni
Department of Neurology, Mount Sinai syndromes (ACS) are also less likely to receive
anticoagulants and thrombolytics (Rosand and Greenberg 2000). rapid effective diagnosis and treatment
School of Medicine,Carlos
One Gustave L. Levy thanSecondary
are men
Correspondence:
Place, Box 1137,
V Serrano Jr
ICH(Ayanian and Epstein
is due to underlying vascular1991; Maynard
malformation, et al 1996;
hemorrhagic Pope
conversion
Coronary Care New
Unit,York, NYEnéas
Av. Dr. 10029,
USA
Carvalho Aguiar, 44 – sala 12 – bloco 2,
et al
of an2000).
ischemic stroke, coagulopathy, intracranial tumor, etc. Arteriovenous malformations
Tel
São+1
Fax
212 241
Paulo
+1 212
- SP9443
- 05403-900, Brazil andRegarding the North American
cavernous malformations account for population,
majority ofthe Women’svascular
underlying Ischemic Syndrome
malformations
Tel +55 11 241 4561
3069 5058
Email sahnir01@mssm.edu
Evaluation (WISE)
(Sutherland and Auer study workshop
2006). An AVM (Hayes
(Figureet al
2)2004; Maseri
is usually 2004; Nabel
a singular lesion et al 2004;
composed
Fax +55 11 3088 3809
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

Vascular
VascularHealth andand
Health Risk Risk
Management 2007:3(5)
Management 701–709 465–475
2006:2(4) 701
465
© 2007
2006Dove
DoveMedical Press
Medical Limited.
Press All rights
Limited. reserved
All rights reserved
Author copy only
Sahni and Weinberger

REVIEW

Coronary artery disease in women: a review


on prevention, pathophysiology, diagnosis, and
treatment
Leila Fernandes Araujo Abstract: Despite numerous studies on women’s cardiac health throughout the past decade, the
Alexandre de Matos Soeiro number of female deaths caused by cardiovascular disease still rises and remains the leading cause
Juliano Lara Fernandes of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular
Antônio Eduardo Pesaro disease, and more specifically coronary artery disease presentations in women, are different than
Carlos V Serrano Jr those in men. In addition, pathology and pathophysiology of the disease present significant
gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the
Heart Institute (InCor), University female population. The reason for this disparity is all steps for female cardiovascular disease
of São Paulo, School of Medicine,
Brazil evaluation, treatment and prevention are not well elucidated; and an area for future research. This
review brings together the most recent studies published in the field of coronary artery disease
in women and points out new directions for future investigation on some of the important issues.
Keywords: coronary artery disease, women, risk factors, prevention, diagnosis, treatment.

Introduction
Figure 1 CT scan showing hemorrhage in the left thalamus secondary to hypertension.
The first female-specific recommendations for preventive cardiology were published in
1999 (Mosca et al 1999). Even though research in the treatment of cardiovascular disease
of an abnormal direct connection between (CVD) had advanced
distal arteries in manyrenal
and disease, areas,disease,
it remains the leading
malignancy, orcause of deathParticular
medication. in women in
veins. AVMs account for only 2% of all ICH mostbutparts
are of the world.
associ- Studieshas
attention have shown
been that 500
directed thousand
towards women die of CVD
oral anticoagulant (OAT)every
ated with an 18% annual rebleed risk (Al-Shahi and Warlow associated hemorrhage due to greater risk for hematoma expan-Heart
year in the United States, somewhat near one death every minute (American
2001). Cavernous malformations are composed Association 2003). Such
of sinusoidal sionindex exceeds
as well not only30
as increased theday
number of deaths
morbidity in men, butrates
and mortality also the
next seven causes of death in women combined, and
vessels and are typically located in within the supratento- (Flibotte et al 2004; Roquer et al 2005; Toyoda et al 2005; more importantly, coronary artery
rial white matter. The annual risk of recurrent disease (CAD) is believed
hemorrhage to be
Steiner andthe major2006).
Rosand cause responsible for these
Metastatic tumors deathsfor
account (American
less
Heart Association 2003). Over a quarter of a million
is only 4.5% (Konziolka and Bernstein 1987). Intracranial than ten percent of ICH located near the grey white junction deaths per year are attributed to CAD
aneurysms usually present with subarachnoid alone hemorrhage
in the United States (Merzcant
with signifi et almass
2004). Although
effect. alreadymalignancy
The primary high, these is figures
usu- are
but anterior communicating artery and middle cerebral artery ally melanoma, choriocarninoma, renal carcinoma, or thyroid and
expected to rise even more during the next decades, due to an increase of diabetes
may also have a parenchymal hemorrhagicobesity, componentas well as the carcinoma
near aging of the(Kondziolka
world population (Merz et1987).
and Berstein al 2004).
Even
the interhemispheric fissure and perisylvian region respectively though women have a higher frequency of chest pain/angina than men, the
(Wintermark and Chaalaron 2003). Embolicincidence ischemic of Clinical
obstructive
strokes CAD in the presentation
female population is lower when compared with
men with similar symptoms
can often demonstrate hemorrhagic conversion without sig- The classic presentation (Kenedy et al 1982; ofDiamond
ICH isetsudden
al 1983;onset
Merzofet aalfocal
1999). In
nificant mass effect (Ott and Zamani 1986).addition, it would appear
Sinus thrombosis that young
neurological deficitwomen with obstructive
that progresses over minutes CAD have with
to hours a worse
prognosis after acute myocardial infarction
should be suspected in patients with signs and symptoms accompanying headache, nausea, vomiting, decreased con- (AMI), whereas older women in similar
suggestive of increased intracranial pressurecircumstances
and radiographic often present with larger
sciousness, numberblood
and elevated of comorbidities that adversely
pressure. Rarely influence
patients pres-
the outcome, when compared to men (Coronado et
evidence of superficial cortical or bilateral symmetric hemor- ent with symptoms upon awakening from sleep. Neurologic al 1997). Women with acute coronary
rhages (Canhoe and Ferro 2005). An underlying syndromescogenial(ACS)or aredefi
alsocits
lessare
likely to receive
related to the rapid
site ofeffective diagnosis
parenchymal and treatment
hemorrhage.
Correspondence: Carlos V Serrano Jr than are men (Ayanian and Epstein 1991; Maynard
acquired coagulopathy causing platelet or coagulation cascade Thus, ataxia is the initial deficit noted in cerebellar hemorrhage, et al 1996; Pope
Coronary Care Unit, Av. Dr. Enéas
dysfunction can result
Carvalho Aguiar, in ICH.
44 – sala Cogenial
12 – bloco 2,
et al 2000).account whereas weakness may be the initial symptom with a basal
disorders
for Hemophilia A, Hemophilia B, and other Regarding
São Paulo - SP - 05403-900, Brazil rare diseases. the North American
ganglia hemorrhage. population, the Women’s
Early progression Ischemicdefi
of neurologic Syndrome
cits
Tel +55 11 3069 5058
Acquired coagulopathy may be attributed to Evaluation
longstanding (WISE)
liver study workshop (Hayes et al 2004; Maseri 2004;
and decreased level of consciousness can be expected in 50% Nabel et al 2004;
Fax +55 11 3088 3809
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

702 Vascular 465–475


Vascular Health and Risk Management 2006:2(4) Health and Risk Management 2007:3(5) 465
© 2006 Dove Medical Press Limited. All rights reserved
Author copy only
Management of ICH

REVIEW

Coronary artery disease in women: a review


on prevention, pathophysiology, diagnosis, and
treatment
Leila Fernandes Araujo Abstract: Despite numerous studies on women’s cardiac health throughout the past decade, the
Alexandre de Matos Soeiro number of female deaths caused by cardiovascular disease still rises and remains the leading cause
Juliano Lara Fernandes of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular
Antônio Eduardo Pesaro disease, and more specifically coronary artery disease presentations in women, are different than
Carlos V Serrano Jr those in men. In addition, pathology and pathophysiology of the disease present significant
gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the
Heart Institute (InCor), University female population. The reason for this disparity is all steps for female cardiovascular disease
of São Paulo, School of Medicine,
Brazil evaluation, treatment and prevention are not well elucidated; and an area for future research. This
review brings together the most recent studies published in the field of coronary artery disease
in women and points out new directions for future investigation on some of the important issues.
Keywords: coronary artery disease, women, risk factors, prevention, diagnosis, treatment.

Introduction
The first female-specific recommendations for preventive cardiology were published in
1999 (Mosca et al 1999). Even though research in the treatment of cardiovascular disease
(CVD) had advanced in many areas, it remains the leading cause of death in women in
most parts of the world. Studies have shown that 500 thousand women die of CVD every
year in the United States, somewhat near one death every minute (American Heart
Association 2003). Such index exceeds not only the number of deaths in men, but also the
next seven causes of death in women combined, and more importantly, coronary artery
Figure 2 Axial T2- weighted MR image showing multiple abnormal flow void (arrow) signals indicating presence of an arteriovenous malformation in the left temporal lobe.
disease (CAD) is believed to be the major cause responsible for these deaths (American
Heart Association 2003). Over a quarter of a million deaths per year are attributed to CAD
of patients with ICH. The progression of alone in the United
neurological deficits StatesCT(Merz are et al 2004).
equally effiAlthough
cacious inalready high, hyperacute
diagnosing these figuresICH are
expected to rise even more during the next decades,
in many patients with an ICH is frequently due to ongoing (⬍6 hours) (Fiebach et al 2004; Kidwell et al 2004). In due to an increase of diabetes and
bleeding and enlargement of the hematoma obesity,during
as wellthe as the
firstagingaddition,
of the world population
in 2004, Fiebach (Merz et al 2004). conducted a mul-
and colleagues
Even though women have a higher
few hours (Kazui et al 1996; Brott et al 1997; Fujii et al 1998). ticenter study and concluded that frequency of chest pain/angina
visual identifithancation
men, theof
incidence of obstructive CAD in the female population
Compared with patients with ischemic stroke, headache and ICH is not difficult with MRI with mean sensitivities = 95% is lower when compared with
vomiting at onset of symptoms is observed men with
threesimilar
times symptoms
more with (Kenedy
expertet readers
al 1982; asDiamond
well asetfialnal-year
1983; Merz et al 1999).
medical studentsIn
often in patients with ICH (Gorlick et addition, it wouldet appear
al 1986; Rathore that young
al (Fiebach et alwomen
2004). MRIwith andobstructive
magneticCAD have aangiog-
resonance worse
prognosis after acute myocardial infarction (AMI),
2002). Despite the differences in clinical presentation between raphy (MRA) can also help elucidate any underlying cause whereas older women in similar
hemorrhagic and ischemic strokes, brain circumstances often present
imaging is required ofwith
the larger numberSometimes
hemorrhage. of comorbidities that adversely
the pattern influence
and topography
to definitively diagnose intracerebral hemorrhage.the outcome, when compared to men (Coronado et al 1997). Women
of bleeding can give important clues about a secondary with acute coronary
syndromes (ACS) are alsocause less likely
of ICH. to receive rapid effective
For example, diagnosis
subarachnoid bloodand treatment
should raise
Diagnosis
Correspondence: Carlos V Serrano Jr than are men (Ayanian and
suspicion Epstein
for a 1991;
ruptured Maynard
aneurysm, et
multiple al 1996;
inferior Pope
frontal
Coronary Care Unit, Av. Dr. Enéas
Carvalho Aguiar,
Computed 44 – sala 12(CT)
tomography – blocois 2,moreetwidely
al 2000).available so and temporal hemorrhages may be seen after head trauma,
CT of the brain has become the initial Regarding
São Paulo - SP - 05403-900, Brazil diagnostic testthe North
of and American
fluid levels population,
within thethe hematoma
Women’s Ischemic
suggest anSyndrome underly-
Tel +55 11 3069 5058
choice Evaluation (WISE) study workshop (Hayes et al 2004; Maseri 2004; Nabel et al 2004;
Fax +55 for
11 ICH. However, recent studies suggest MRI and ing coagulopathy (Figure 3). Active contrast extravasation
3088 3809
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

Vascular Health and Risk Management 2007:3(5)


Vascular Health and Risk Management 2006:2(4) 465–475 703
465
© 2006 Dove Medical Press Limited. All rights reserved
Author copy only
Sahni and Weinberger

REVIEW
into the hematoma seen with CT angiography may predict aspiration, impending ventilatory failure (PaO2 ⬍ 60 mmHg
hematoma expansion and is predictive of poor outcome or pCO2 ⬎ 50 mmHg), and signs of increased intracranial
(Becker et al 1999; Murai et al 1999). Angiography is not pressure. (Broderick et al 1999) Emergency measures for

Coronary artery disease in women: a review


required for older hypertensive patients with hemorrhages ICP control are appropriate for stuporous or comatose
in deep subcortical structures with no findings suggestive patients, or those who present acutely with clinical signs

on prevention, pathophysiology, diagnosis, and


of an underlying structural lesion. Secondary intracerebral of brainstem herniation. The head should be elevated to 30
hemorrhage should be suspected in patients ⬍45 years of degrees, 1.0–1.5 g/kg of 20% mannitol should be given by

treatment
age, no risks for hypertensive hemorrhage, presence of a rapid infusion, and the patient should be hyperventilated
subarachnoid hemorrhage, prominent vascular structures, to a pCO2 of 30–35 mmHg. (Allen and Ward 1998) These
perisylvian or interhemispheric hemorrhage and angiography measures are designed to lower ICP as quickly as possible
should be pursued. Angiography should always be considered prior to a definitive neurosurgical procedure (craniotomy,
Leilanon-hypertensive
in young Fernandes Araujo Abstract:
patients with ICH Despite
who have nonumerous studies on women’s
ventriculostomy, cardiac health
or placement of anthroughout the pastcan
ICP monitor) decade,
be the
Alexandre
obvious explanationdefor
Matos Soeiro number
their hemorrhage,
of female deaths caused by cardiovascular disease still rises and remains the leading cause
or when the only done. A number of these patients will present after a fall so
Juliano Lara Fernandes of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular
risk factor is cocaine or sympathomimetic-drug use (Halpin particular attention should be directed to lacerations, skeletal
disease, and more specifically coronary artery disease presentations in women, are different than
et alAntônio
1994; GriffiEduardo Pesaro
ths et al 1997; Zhu et al 1997; Broderick fractures, stabilization of the cervical spine.
Carlos1999).
V Serrano Jr those in men. In addition, pathology and pathophysiology of the disease present significant
and Adams gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the
Heart Institute (InCor), University female population. TheBlood
reason forpressure
this disparity is all steps for female cardiovascular disease
Management
of São Paulo, School of Medicine,
Elevated
evaluation, treatment and blood
prevention pressure
are not is seen inand
well elucidated; 46%–56%
an area foroffuture
patients with This
research.
Brazil
Emergency management review brings together the
ICH.most recent studies
(Dandapani published
et al 1995) Itin remains
the field of coronary
unclear artery disease
if elevated
ICH is a neurological emergency and initial in women and points outblood
management new directions
pressurefordirectly
future investigation on some ofexpansion
causes hematoma the important issues.
but
should be focused on assessing the patients Keywords: coronary artery
airway, breathing disease,
studies have women, risk factors,
shown elevated prevention,
systolic, diagnosis,
diastolic, and treatment.
mean
capability, blood pressure and signs of increased intracranial arterial pressure are associated with a poor outcome in ICH
pressure. The patient should be intubated based on risk of (Terrayama et al 1997; Leonardi-Bee et al 2002; Vemmos
Introduction
The first female-specific recommendations for preventive cardiology were published in
1999 (Mosca et al 1999). Even though research in the treatment of cardiovascular disease
(CVD) had advanced in many areas, it remains the leading cause of death in women in
most parts of the world. Studies have shown that 500 thousand women die of CVD every
year in the United States, somewhat near one death every minute (American Heart
Association 2003). Such index exceeds not only the number of deaths in men, but also the
next seven causes of death in women combined, and more importantly, coronary artery
disease (CAD) is believed to be the major cause responsible for these deaths (American
Heart Association 2003). Over a quarter of a million deaths per year are attributed to CAD
alone in the United States (Merz et al 2004). Although already high, these figures are
expected to rise even more during the next decades, due to an increase of diabetes and
obesity, as well as the aging of the world population (Merz et al 2004).
Even though women have a higher frequency of chest pain/angina than men, the
incidence of obstructive CAD in the female population is lower when compared with
men with similar symptoms (Kenedy et al 1982; Diamond et al 1983; Merz et al 1999). In
addition, it would appear that young women with obstructive CAD have a worse
prognosis after acute myocardial infarction (AMI), whereas older women in similar
circumstances often present with larger number of comorbidities that adversely influence
the outcome, when compared to men (Coronado et al 1997). Women with acute coronary
syndromes (ACS) are also less likely to receive rapid effective diagnosis and treatment
Correspondence: Carlos V Serrano Jr than are men (Ayanian and Epstein 1991; Maynard et al 1996; Pope
Coronary Care Unit, Av. Dr. Enéas
Carvalho Aguiar, 44 – sala 12 – bloco 2,
et al 2000).
São Paulo - SP - 05403-900, Brazil Regarding the North American population, the Women’s Ischemic Syndrome
Tel +55 11 3069 5058
Evaluation (WISE) study workshop (Hayes et al 2004; Maseri 2004; Nabel et al 2004;
Fax
Figure +55
3 CT scan11showing
3088 large
3809left parietal lobe lobar hemorrhage with a fluid level (arrow) after the patient received r-TPA.
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

704 Vascular 465–475


Vascular Health and Risk Management 2006:2(4) Health and Risk Management 2007:3(5) 465
© 2006 Dove Medical Press Limited. All rights reserved
Author copy only
Management of ICH

REVIEW
et al 2004). However, physicians have been reluctant to to the level of anticoagulation. Heparin can be inactivated
treat hypertension in ICH patients because the fear of by 1 mg of protamine sulfate for every 100 IU of heparin
overaggressive treatment of blood pressure may decrease administered (Wakefield and Stanley 1996). FFP should

Coronary artery disease in women: a review


cerebral perfusion pressure and theoretically worsen brain not be used to correct heparin related coagulopathy because
injury, particularly in the setting of increased intracranial FFP contains heparin binding antithrombin III (AT-III)

on prevention, pathophysiology, diagnosis, and


pressure. In 1999, a special group consisting of healthcare which may prolong the anticoagulated status (Badjatia and
professionals from the American Heart Association Stroke Rosand 2005). Warfarin prevents recycling of vitamin K

treatment
Council addressed these 2 rational theoretical concerns and indirectly inhibits synthesis of vitamin K dependent
while attempting to write guidelines for the management coagulation factors. Replenishing vitamin K via the oral or
of intracerebral hemorrhage. The task force recommended intravenous route helps reverse the effect of warfarin but an
maintaining a mean arterial pressure below 130 mmHg in effective response may be delayed over 24 hours. Concomi-
Leila Fernandes
patients Araujo
with a history of hypertensionAbstract: Despite numerous
(level of evidence V, nant studies
useon ofwomen’s
vitamincardiac
K withhealth
FFP,throughout the pastor
cryoprecipitate, decade, the
clotting
Alexandre
grade de Matos Soeiro
C recommendation).
number of female deaths caused by cardiovascular disease still rises and remains the leading cause
In patients with elevated ICP who factor concentrates are recommended to hasten reversal
Juliano Lara Fernandes of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular
have an ICP monitor, cerebral perfusion pressure (MAP–ICP) of warfarin induced coagulopathy. Considering the short
Antônio Eduardo Pesaro disease, and more specifically coronary artery disease presentations in women, are different than
should be kept ⬎70 mmHg (level of evidence V, grade C half-life of coagulation factors at least 5–20 mg of vitamin
Carlos V Serrano Jr those in men. In addition, pathology and pathophysiology of the disease present significant
recommendation) (Broderick et al 1999). K is required to sustain reversal of anticoagulation. Intrave-
gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the
Heart Institute (InCor), University female population. The reason nous foradministration
this disparity is of all vitamin
steps for K should
female be limited disease
cardiovascular due to
Early
Brazil
hemostatic therapy
of São Paulo, School of Medicine,
evaluation, treatment and prevention are not well elucidated; and an area for future research.acute
concerns of allergic and anaphylactic reactions. In an This
In the past, early neurologic deterioration review brings in ICH setting,
wasthe most
together recentvitamin K shouldinnot
studies published the be
fieldadministered
of coronary arterysubcutane-
disease
attributed to edema and mass effect around in women theand points out newously
hematoma. directions
becausefor future investigation
reversal on some of is
of anticoagulation theneither
important rapidissues.
nor
Pathological, CT, and SPECT studies suggest Keywords: coronary arteryreliable
that continuous disease,(Steiner
women,etrisk factors,However,
al 2006). prevention, thediagnosis,
variable treatment.
content of
rebleeding into congested damaged tissue is associated with vitamin K-dependent clotting factors in FFP and the effects
poor clinical outcome and is now an exciting new target of of dilution have raised concerns that a coagulopathic state
treatment (Fisher 1971; Kazui et al 1996; Introduction
Fujii et al 1998; may persist despite correction of the international normalized
The
Becker et al 1999; Mayer 2005). Recent interest in first female-specific
hemostatic recommendations
ratio (INR) (Makris for preventive
et al 1997). cardiology
It is not were
clear published
at this time in
therapy is based on early hematoma growth 1999often(Mosca seen et al 1999). Even
within whetherthough research incomplex
prothrombin the treatment of cardiovascular
concentrate disease
is more reliable
(CVD) had advanced in many areas, it remains the
six hours of onset of ICH in 14%–38% of patients (Kazui than FFP in repleting coagulation factors but it has proven to leading cause of death in women in
et al 1996; Brott et al 1997; Fujii et al most
1998;parts of the world.
Flibotte et al Studies
correct have
theshown that 500
INR faster thanthousand
FFP which women die of
reduces theCVD every
incidence
year in the United States, somewhat near one
2004; Roquer et al 2005). Initial efforts should be directed and extent of hematoma expansion (Fredriksson et al 1992;death every minute (American Heart
towards identifying thrombolytic, antiplateletAssociation 2003). Such index
or anticoagu- Huttnerexceeds
et alnot only Use
2006). the number of deathsagents
of antiplatelet in men, but also
prior to ICHthe
next seven causes of death in women combined, and
lant use and reversing their effects. The biologic half-life of is a risk factor for continuous bleeding and poor outcome more importantly, coronary artery
recombinant tissue plasminogen activator disease (CAD)
(rt-PA) is believed
at the site so to it
beisthe major cause
reasonable responsible
to treat for thesewith
these patients deaths (American
platelet infu-
Heart Association 2003). Over a quarter of a million
of the thrombus is limited to 45 minutes and accordingly sions and desmopressin (Janssen and van der Meulen 1996; deaths per year are attributed to CAD
hemorrhagic complications from rt-PA aloneoccurin thewithin
Unitedthe StatesSaloheimo
(Merz et alet2004). Although already high, these figures are
al 2006).
expected
first few hours of use. Information is scarce to guide recom- to rise even more during
Antifibrinolytic agentsdue
the next decades, such to as
ane-aminocaproic,
increase of diabetes and
tranex-
mendations about treatment of hemorrhagic obesity, complications
as well as the agingemic of the world
acid, population
aprotinin, and(Merz et al 2004).
activated recombinant Factor VII
Even though women have a higher frequency
of thrombolytic therapy (levels of evidence III through V). (rFVIIa) have been receiving attention for early of chest pain/angina than men, the
hemostatic
According to guidelines devised by incidence the American of obstructive
Heart CAD therapy in the female population
in patients is lower when
with no underlying comparedHow-
coagulopathy. with
men with similar symptoms (Kenedy et al 1982; Diamond
Association Stroke Council, if bleeding is suspected the fol- ever, rFVIIa is the only agent whose role in treating primary et al 1983; Merz et al 1999). In
lowing measures should be taken: (1) blood addition,should it would
be drawn appearICHthathas young
beenwomenevaluated within obstructive
the randomized CADplacebo
have acontrol
worse
prognosis after acute myocardial infarction (AMI),
to measure the patient’s hematocrit, hemoglobin, partial trial. The Novoseven Phase II trial was an international, whereas older women in similar
thromboplastin time, prothrombin time/INR, circumstances
plateletoftencount,present with larger double-blinded
multicenter, number of comorbidities
trial that that adversely
clearly influencea
demonstrated
the outcome, when compared to men (Coronado
and fibrinogen (2) blood should be typed and cross-matched reduction in early hematoma expansion in patients adminis-et al 1997). Women with acute coronary
if transfusions are needed (at least 4 Usyndromes
of packed(ACS) red bloodare alsotered
less likely
rFVIIatowithinreceive rapid effective
4 hours of symptom diagnosis and treatment
onset compared with
Correspondence: Carlos V Serrano Jr than are men (Ayanian and Epstein 1991;
cells, 4–6 U of cryoprecipitate or fresh frozen plasma, and placebo. In fact, the hemostatic effect was more pronounced Maynard et al 1996; Pope
Coronary Care Unit, Av. Dr. Enéas
1Carvalho
U of single donor
Aguiar, 44 – salaplatelets)
12 – bloco(Adams
2,
et alet2000).
al 1996). These with incremental doses of rFVIIa (Mayer et al 2005). Despite
São Paulo - SP - 05403-900, Brazil Regarding
therapies should be made available for urgent administration. the NorththeseAmericanpromisingpopulation, the Women’s
results, early results from Ischemic
the Phase Syndrome
III Fast
Tel +55 11 3069 5058
The risk of intracerebral hemorrhage Evaluation
with heparin (WISE)
is relatedstudy trial
workshopshowed (Hayes
use etrFVIIa
of al 2004;did Maseri
not 2004;
alter Nabel
severe et al 2004;
disability or
Fax +55 11 3088 3809
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

Vascular Health and Risk Management 2007:3(5)


Vascular Health and Risk Management 2006:2(4) 465–475 705
465
© 2006 Dove Medical Press Limited. All rights reserved
Author copy only
Sahni and Weinberger

REVIEW
mortality rates at 90 days (Forbes 2007). Complete results suggested use of intraventricular thrombolysis within 72 hours
from the Phase III FAST trial are expected later this year. of IVH may help drain the blood filled ventricles, speed clot
resolution and decrease 30-day mortality rate (Naff et al 2000;

Coronary artery disease in women: a review


Management of ICP
Elevated ICP is defined as intracranial pressure ⬎20 mmHg
Naff et al 2004). Patients are currently being recruited for
Phase III trials assessing thrombolytic use in intraparenchymal

on prevention, pathophysiology, diagnosis, and


for over 5 minutes. Large volume ICH is commonly
associated with high ICP and brain tissue shifts related to
and intraventricular hemorrhage.

treatment
ICP gradients. This problem can be exacerbated by intra- Anticonvulsant therapy
ventricular hemorrhage, which leads to acute obstructive The 30-day risk of seizures after ICH is about 8%. Seizures
hydrocephalus. The therapeutic goal of treating elevated ICP most commonly occur at the onset of hemorrhage and may
is to maintain ICP ⬍ 20 mmHg while maintaining cerebral even be the presenting symptom. Lobar location is an inde-
Leila pressure
perfusion Fernandes ⬎70Araujo
mmHg. When ICP Abstract: Despite numerous
is monitored, pendent studies on women’s
predictor cardiac
of early health throughout
seizures (Passero the et past decade, the
al 2003).
use Alexandre
of a standardde Matos Soeiro number of female deaths caused by cardiovascular disease still rises and remains the leading cause
management algorithm results in better Although, no randomised trial has addressed the efficacy of
Juliano Lara Fernandes of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular
control, fewer interventions, and shorter duration of therapy. prophylactic antiepileptic in ICH patients, the Stroke Council
Antônio Eduardo Pesaro disease, and more specifically coronary artery disease presentations in women, are different than
Initially, acute and sustained increase in ICP should prompt of the American Heart Association suggest prophylactic anti-
Carlos V assess
Serrano those in men. In addition, pathology and pathophysiology of the disease present significant
Jr for a definitive
a repeat CT to the need neurosurgi- epileptic treatment may be considered for 1 month in patients
gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the
Heart Institute
cal procedure. An (InCor), University
intravenous sedative such
femaleaspopulation.
propofol Thewith intracerebral
reason hemorrhage
for this disparity andfor
is all steps discontinued if no seizures
female cardiovascular disease
of São Paulo, School of Medicine,
(0.6–6.0 mg/kg/h) or fentanyl (0.5–3.0 µg/kg/h) evaluation,should be
treatment are
and noted
prevention (Broderick
are not well et al 1999;
elucidated; Temkin
and an area2001).
for Acute
future man- This
research.
Brazil
given to the agitated patient to attain a review motionlessbringsstate. agement
together the of seizures
most recent studies entail
publishedadministering
in the field ofintravenous loraz-
coronary artery disease
in women and points out new directions for future investigation on some of the important issues.
Thereafter, therapy should be directed at controlling blood epam (0.05–0.10 mg/kg) followed by an intravenous loading
pressure with vasopressors such as dopamine Keywords: coronary artery
and phenyl- dose of disease, women,
phenytoin or risk factors, prevention,
fosphenytoin (15–20 mg/kg),diagnosis, treatment.
valproic
ephrine if the CPP is ⬍ 70 mmHg or with antihypertensive acid (15–45 mg/kg), or phenobarbital (15–20 mg/kg).
agents if the CPP is ⬎ 70 mmHg. If ICP does not respond to
sedation and cerebral perfusion management, Introduction
osmotic agents Fever control
and hyperventilation should be considered (MckinleyThe first female-specific
et al Fever recommendations
after ICH is common for preventive
and shouldcardiology were published
be treated aggres- in
1999). Of the 3 osmotic agents frequently1999 used(Mosca et al 1999).
(mannitol, Even
sively though research
because in the treatment
it is independently of cardiovascular
associated with a poor disease
glycerol, and sorbitol), each has characteristic advantages outcome (Schwarcz et al 2001). Sustained fever in excess of in
(CVD) had advanced in many areas, it remains the leading cause of death in women
and disadvantages. Sorbitol and glycerol are most parts of thebyworld.
metabolized Studies
38.3 have shown
°C (101.0 °F) shouldthat be
500treated
thousand withwomen die of CVD
acetaminophen andevery
the liver and interfere with glucose metabolism. However, cooling blankets. Patients should be physically examined andHeart
year in the United States, somewhat near one death every minute (American
sorbitol is infrequently used due to a short Association
half life and2003).
poor Such index
should exceedslaboratory
undergo not only the number
testing of deathstoindetermine
or imaging men, but also
the the
next seven causes of death in women combined, and
penetration into the cerebrospinal fluid (CSF). Glycerol has source of infection. Fever of neurologic origin is diagnosis more importantly, coronary artery
a half-life less than one hour but it penetrates disease
into(CAD)
the cere- is believed to be theand
of exclusion majormaycause responsible
be seen when bloodfor these deathsinto
extends (American
the
brospinal fluid the best. Mannitol is commonly used because subarachnoid or intraventricular (Commichau and ScarmeasCAD
Heart Association 2003). Over a quarter of a million deaths per year are attributed to
it is renally metabolized, has a half-life up alone
to 4inhours,
the United
and States
2003).(Merz et al 2004).
Intracerebral Although
hemorrhage alreadywith
patients high, these figures
persistent fever are
achieves intermediate concentrations within the CSF (Nau that is refractory to acetaminophen and without infectious and
expected to rise even more during the next decades, due to an increase of diabetes
2000). Large ICH associated with elevated obesity, as well as the cause
intracranial aging of maytherequire
world population
cooling devices (Merztoetbecome
al 2004). normothermic.
Even though women have a higher frequency
pressure refractory to these measures is fatal in most patients Adhesive surface-cooling systems and endovascular of chest pain/angina thanheat-
men, the
but a barbiturate coma may considered as incidence of obstructive
a last resort to exchangeCAD in the female
catheters arepopulation is lower when
better at maintaining compared with
normothermia
try to reduce intracranial pressure (Broderick et al 1999; than conventional treatment. However, it is stilletunclear
men with similar symptoms (Kenedy et al 1982; Diamond et al 1983; Merz al 1999). In
Mckinley et al 1999). Corticosteroids are not addition, it would appear
recommended whether thatmaintaining
young women with obstructive
normothermia CAD have
will improve a worse
clinical
prognosis after acute
in the management of ICH because they have been proven outcome (Dringer 2004). myocardial infarction (AMI), whereas older women in similar
to offer no benefit in randomized trials (Tellez circumstances
and Bauer often present with larger number of comorbidities that adversely influence
1973; Poungvarin et al 1987). the outcome, when Deeptovenous
compared men (Coronadothrombosis
et al 1997). Womenprophylaxis with acute coronary
Ventricular drains should be used in patients syndromes
with or (ACS)
at risk areImmobilized
also less likelystate
to receive
due torapid limb effective
paresisdiagnosis
predisposesand treatment
ICH
Correspondence: Carlos V Serrano Jr than are men (Ayanian and Epstein 1991;
for hydrocephalus. Drainage can be initiated and terminated patients for deep vein thrombosis and pulmonary embolism. Maynard et al 1996; Pope
Coronary Care Unit, Av. Dr. Enéas
according to clinical
Carvalho Aguiar, 44performance and ICP
– sala 12 – bloco
et al 2000).
2, values. The volume Intermittent pneumatic compression devices and elastic
São Paulo - SP - 05403-900, Brazil
of IVH strongly affects morbidity and mortality Regarding
at 30-days the North American
stockings shouldpopulation,
be placed onthe Women’s(Lacut
admission Ischemic Syndrome
et al 2005).
Tel +55 11 3069 5058
(Tuhrim et al111988). Evaluation
urokinase(WISE)
have study workshop (Hayestrialet al by2004; Maseriand2004; Nabel et al 2004;
Fax +55 3088 Preliminary
3809 studies with A small prospective Boeer colleagues using
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

706 Vascular 465–475


Vascular Health and Risk Management 2006:2(4) Health and Risk Management 2007:3(5) 465
© 2006 Dove Medical Press Limited. All rights reserved
Author copy only
Management of ICH

REVIEW
low-dose heparin on hospital day 2 to prevent thromboebolic have demonstrated that stereotactic aspiration and thromboly-
complications in ICH patients significantly lowered the inci- sis spontaneous intracerebral hemorrhage appears to be safe
dence of pulmonary embolism and no increase in rebleeding and effective in the reduction of ICH volume (Teernstra et al

Coronary artery disease in women: a review


was observed (Boeer et al 1991). 2003; Barrett et al 2005; Vespa et al 2005). The National
Institute of Health (NIH) has sponsored the Minimally

on prevention, pathophysiology, diagnosis, and


Surgical management Invasive Surgery Plus rtPA for Intracerebral Hemorrhage
Numerous surgical trials since the 1960s offered conflict- Evacuation (MISTIE) trial to determine the safety of using a

treatment
ing results and until recently no firm conclusions could be combination of minimally invasive surgery and clot lysis with
reached regarding the operative management of intracere- rt-PA to remove supratentorial primary ICH and compare
bral hemorrhage. In 1995 randomization for the landmark efficacy to conventional medical management. The MISTIE
Surgical Trial in Intracerebral Hemorrhage (STICH) had trial is an open-label randomized treatment trial which is
Leila Fernandes
commenced. Araujo
This trial Abstract: multicenter
was an international, Despite numerouscurrently
studies onenrolling
women’s cardiac
patients health throughoutcenters
at multiple the pastwithin
decade,thethe
Alexandre
trial de Matos1033
that randomized Soeiro number of female deaths caused by cardiovascular disease still rises and remains the leading cause
patients with spontaneous United States (NIH 2001).
Juliano Lara Fernandes of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular
supratentorial intracerebral hemorrhage within twenty-
Antônio disease, and more specifically coronary artery disease presentations in women, are different than
four hours Eduardo
to early surgeryPesaro or conservative best medical Conclusion
Carlos VSize,
therapy. Serrano
location, Jr and volume those
of
in men. In addition, pathology and pathophysiology of the disease present significant
hemorrhage were Currently,
gender differences, which leads no specifi
to difficulties c therapies
concerning diagnosis, improve
treatmentthe andoutcome
outcome of after
the
Heart Institute
similar in both(InCor),
treatment University
groups. Patients randomized to ICH. Although rFVIIa limits hematoma
female population. The reason for this disparity is all steps for female cardiovascular disease expansion, early
of São Paulo, School of Medicine,
early surgery had their hematoma evacuated within
evaluation, twenty-
treatment Phase III
and prevention areresults
not well failed to show
elucidated; andreduction
an area forin severe
future disability
research. This
Brazil
four hours of randomization by the review method of choice
brings togetherofthe most recent studies
or mortality ratespublished
at 90 days. in the
New field of coronary
trials evaluating artery
thedisease
safety
the designated neurosurgeon. In 77%inofwomen cases,and points out newofdirections
craniotomy for future investigation
the combination of minimally on some
invasiveof thesurgery
important andissues.
clot
was the surgical procedure and the remainder Keywords: of coronary
cases had arterylysis
disease,
withwomen,
r-tPArisk factors, prevention,
to remove intracerebral diagnosis, treatment.
hemorrhage are
hematoma removal by burr hole, endoscopy, or stereotaxy currently underway.
in similar numbers. Thus, the STICH Trial is primarily a
trial of craniotomy for ICH removal and Introduction
left the role of less
The first female-specific Referencesfor preventive cardiology were published in
invasive surgery to remove ICH unanswered. Structured recommendations
Adams HP, Brott TG, et al. 1996. Guidelines for thrombolytic therapy for
postal questionnaires were used to assess 1999 (Mosca
outcomes et al with
1999). Evenacutethough research
stroke: in the treatment
a supplement of cardiovascular
to the guidelines for the managementdiseaseof
(CVD)
the Glasgow Coma Scale, modified Rankin Scale, Barthel had advanced in many areas,
patients it
withremains the
acute ischemic leading
stroke. A cause of
statement death in women
for healthcare in
profes-
sionals from a special writing group of the Stroke Council, American
index, and mortality at 6-months. Overall, most parts of the world.
the STICH trial Studies have shown that 500 thousand women die of CVD every
Heart Association. Circulation, 94:1167–74.
year in
revealed no benefit from early craniotomy in supratentorial the United States, somewhat
Allen CH, Wardnear one An
JD. 1998. death every minute
evidence-based approach(American
to managementHeart
of
Association 2003).con- increased intracranial pressure. Crit Care Clin,
Such index exceeds not only the number of deaths in men, but also the 14:485–95.
intracerebral hemorrhage when compared to initial Al-Shahi R, Warlow C. 2001. A systematic review of the frequency and
servative management. Of the prespecified subgroups thatdeath in prognosis
next seven causes of women combined, and more
of the arteriovenous importantly,
malformation of thecoronary
brain in artery
adults.
were examined, patients with an ICHdisease within(CAD) is believed to be the major cause responsible for these deaths (American
Brain, 124:1900–26.
a centimeter Auer RN, Sutherland GR. 2005. Primary intracerebral hemorrhage: patho-
of the cortical surface showed a benefi Heart
t forAssociation
early surgery. 2003). Overphysiology.
a quarter of a million deaths per year are attributed to CAD
Can J Neurol Sci, 32:S3–12.
However, the statistical testing of this alone in the United
subgroup was not StatesBadjatia
(Merz N, et Rosand
al 2004). Although
J. 2005. already
Intracerebral high, these
Hemorrhage. The figures are
Neurologist,
expected to rise even more 11:311–24.
during the next decades, due to an increase of diabetes and
adjusted for in the multiple subgroup comparisons in this Barrett RJ, Hyssain R, et al. 2005. Frameless stereotactic aspiration and
trial. In addition, early surgery was delayed obesity, aswith wellmedian
as the aging ofthrombolysis
the world population
of spontaneous(Merz et al 2004).
intracerebral hemorrhage. Neurocrit
Even though women have a
Care,higher
3:237–45.frequency of
time from onset to treatment for early surgery group was Becker KJ, Baxter AB, et al. 1999. Extravasation of radiographic chest pain/angina than men, the
contrast is
30 hours and that may have affected theincidence outcomeof obstructive CADanin
(Broderick the female population is lower when compared with
independent predictor of death in primary intracerebral hemorrhage.
2005; Mendelow et al 2005). men with similar symptoms (Kenedy et al 1982; Diamond et al 1983; Merz et al 1999). In
Stroke, 30:2025–32.
addition, it to
would appear Boeer
that youngE,women
A, Voth et al. 1991. Earlyobstructive
with heparin therapy CAD in patients
have with spon-
a worse
In contrast, infratentorial hemorrhages seem benefi t taneous intracerebral haemorrhage. J Neurol Neurosurg Psychiatry,
from early surgery. Most neurosurgeons prognosis
believeafter acute myocardial
cerebellar infarction (AMI), whereas older women in similar
54:466–7.
hemorrhages greater than 3 centimeters circumstances
benefit from often present with larger
early
Broderick number
JP, Adams HP,ofetcomorbidities
al. 1999. Guidelines that adversely influence
for the management of
spontaneous intracerebral hemorrhage: a statement for health profes-
surgical intervention because of the signifi the outcome,
cant risk when compared to
of brain- men (Coronado et al 1997). Women with acute coronary
sionals from a special writing group of the Stroke Council, American
stem compression and obstructive hydrocephalus syndromes (ACS) are also lessHeart
within likely to receive
Association. rapid
Stroke, effective diagnosis and treatment
30:905–15.
Correspondence: Carlos V Serrano Jr than are men (Ayanian Broderick
and JP. 2005. The1991;
Epstein STICH trial: what does et
Maynard it tellalus and
1996;wherePope
do we
24 hours (Ott et al 1974). go from here? Stroke, 36:1619–20.
Coronary Care Unit, Av. Dr. Enéas
NewAguiar,
Carvalho areas of44 surgical
– sala 12research
et al 2000).
are focused
– bloco 2, on combination Brott T, Broderick J, et al. 1997. Early hemorrhage growth in patients with
of minimally invasive surgery and and clot lysis withthe
Regarding North American population,
São Paulo - SP - 05403-900, Brazil intracerebral hemorrhage.the Women’s
Stroke, 28:1–5. Ischemic Syndrome
r-tPA
Tel +55 11 3069 5058 Campbell GJ, Roach M. 1981. Fenestrations in the internal elastic lamina at
to Evaluation (WISE) study workshop (Hayes et al 2004; Maseri 2004; Nabel et al 2004;
Faxremove
+55 11 intracerebral
3088 3809 hemorrhage. Small preliminary trials bifurcations of human cerebral arteries. Stroke, 12:489–96.
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

Vascular Health and Risk Management 2007:3(5)


Vascular Health and Risk Management 2006:2(4) 465–475 707
465
© 2006 Dove Medical Press Limited. All rights reserved
Author copy only
Sahni and Weinberger

REVIEW
Canhoe P, Ferro JM. 2005. Causes and predictors of death in cerebral venous Mayer S, Commichau C, et al. 2001. Clinical trial of an air-circulating
thrombosis. Stroke, 6:1720–5. cooling blanket for fever control in critically ill neurologic patients.
Commichau C, Scarmeas N. 2003. Risk factors for fever in the neurologic Neurology, 56:292–8.
intensive care unit. Neurology, 60:837–41. Mayer S, Ligenelli A, et al. 1998. Perilesional blood flow and edema forma-

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Counsell C, Boonyakarnkul S, et al. 1995. Primary intracerebral hemor-
rhage in the Oxfordshire Community Stroke Project. Cerebrovasc
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McKinley BA, Parmley CL, et al. 1999. Standardized management of intra-
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in intracerebral hemorrhage. Stroke, 26:21–4.
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Mendelow AD, Gregson BA, et al. 2005. Early surgery versus initial
conservative treatment in patients with spontaneous supratentorial
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blood the
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by cardiovascular disease still rises and remains the leading cause
controlled trial. Neurosurgery, 54:577–83.
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Naff N, Carhuapoma Novel
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for and
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Stroke, 29:1160–6. Ott KH, Kase CS, et al. 1974. Cerebellar hemorrhage: diagnosis and treat-
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Introduction
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1999
treated neurocritical care patients with intracerebral (Moscarelated
hemorrhage et al 1999). Even though
to evaluate theresearch
feasibilityinand thesafety
treatment of cardiovascular
of aggressive antihypertensive disease
to oral anticoagulant therapy: comparison of acute (CVD) had advanced
treatment strate- in many
treatmentareas, it remains
in patients the leading
with acute cause
intracerebral of deathJinIntensive
hemorrhage. women in
gies using vitamin K, fresh frozen plasma, and prothrombin complex Care Med, 20:34–42.
concentrates. Stroke, 37:1465–70.
most parts of the world. Studies have shown that 500 thousand women die of CVD every
Qureshi AI, Tuhrim S, et al. 2001. Spontaneous intracerebral hemorrhage.
Janssen MJ, van der Meulen J. 1996. The bleedingyear risk inin chronic
the United
hae- States, somewhat
N Engl near one death every minute (American Heart
J Med, 344:1450–60.
modialysis: preventive strategies in high-risk patients. Neth J Med, Rabinstein AA,
Association 2003). Such index exceeds not only Atkinson JL, et the
al. 2002.
numberEmergency
of deaths craniotomy
in men,inbutpatients
also the
48:198–207. worsening due to expanded cerebral hematoma: to what purpose?
next seven
Kazui S, Naritomi H, et al. 1996. Enlargement of spontaneous intracerebral causes of death in women combined,
Neurology, 58:1367–72. and more importantly, coronary artery
hemorrhage. Incidence and time course. Stroke, disease
27:1783–7. (CAD) is believed to be the major cause responsible for these deaths (American
Rathore SS, Hinn AR, et al. 2002. Characterization of incident stroke signs
Kidwell CS, Chalela JA, et al. 2004. Comparison of MRI and CT for detec- and symptoms: findings from the atherosclerosis risk in communities
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population, the Women’s Ischemic Syndrome
Tel +55 11 3069 5058
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Fax +55 11 3088 3809
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

708 Vascular 465–475


Vascular Health and Risk Management 2006:2(4) Health and Risk Management 2007:3(5) 465
© 2006 Dove Medical Press Limited. All rights reserved
Author copy only
Management of ICH

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Tellez H, Bauer RB. 1973. Dexamethasone as treatment in cerebrovascular Vespa P, McArthur D, et al. 2005. Frameless stereotactic aspiration and

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tion of hemorrhage volume and neurological improvement. Neurocrit
Care, 2:274–81.

on prevention, pathophysiology, diagnosis, and


antiepileptic drugs: meta-analysis of controlled trials. Epilepsia,
42:515–24.
Terayama Y, Tanahashi N, et al. 1997. Prognostic value of admission
Wakefield TW, Stanley JC. 1996. Intraoperative heparin anticoagulation
and its reversal. Semin Vasc Surg, 9:296–302.
Wintermark MUA, Chaalaron M, et al. 2003. Multislice computerized

treatment
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28:1185–8.
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Toyoda K, Okado Y, et al. 2005. Antiplatelet therapy contributes to acute J Neurosurg, 98:828–36.
deterioration of intracerebral hemorrhage. Neurology, 65:1000–4. Zhu XL, Chan MS, Poon WS. 1997. Spontaneous intracranial hemorrhage:
Tuhrim S, Dambrosia JM, et al. 1988. Prediction of intracerebral hemorrhage which patients need diagnostic cerebral angiography? A prospective
Leila Fernandes
survival. Ann Neurol,Araujo
24:258–63. Abstract: Despite numerous studies
study on women’s
of 206 cardiac
cases and health
review of thethroughout the past
literature. Stroke, decade, the
28:1406–9.
Alexandre de Matos Soeiro number of female deaths caused by cardiovascular disease still rises and remains the leading cause
Juliano Lara Fernandes of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular
Antônio Eduardo Pesaro disease, and more specifically coronary artery disease presentations in women, are different than
Carlos V Serrano Jr those in men. In addition, pathology and pathophysiology of the disease present significant
gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the
Heart Institute (InCor), University female population. The reason for this disparity is all steps for female cardiovascular disease
of São Paulo, School of Medicine,
Brazil evaluation, treatment and prevention are not well elucidated; and an area for future research. This
review brings together the most recent studies published in the field of coronary artery disease
in women and points out new directions for future investigation on some of the important issues.
Keywords: coronary artery disease, women, risk factors, prevention, diagnosis, treatment.

Introduction
The first female-specific recommendations for preventive cardiology were published in
1999 (Mosca et al 1999). Even though research in the treatment of cardiovascular disease
(CVD) had advanced in many areas, it remains the leading cause of death in women in
most parts of the world. Studies have shown that 500 thousand women die of CVD every
year in the United States, somewhat near one death every minute (American Heart
Association 2003). Such index exceeds not only the number of deaths in men, but also the
next seven causes of death in women combined, and more importantly, coronary artery
disease (CAD) is believed to be the major cause responsible for these deaths (American
Heart Association 2003). Over a quarter of a million deaths per year are attributed to CAD
alone in the United States (Merz et al 2004). Although already high, these figures are
expected to rise even more during the next decades, due to an increase of diabetes and
obesity, as well as the aging of the world population (Merz et al 2004).
Even though women have a higher frequency of chest pain/angina than men, the
incidence of obstructive CAD in the female population is lower when compared with
men with similar symptoms (Kenedy et al 1982; Diamond et al 1983; Merz et al 1999). In
addition, it would appear that young women with obstructive CAD have a worse
prognosis after acute myocardial infarction (AMI), whereas older women in similar
circumstances often present with larger number of comorbidities that adversely influence
the outcome, when compared to men (Coronado et al 1997). Women with acute coronary
syndromes (ACS) are also less likely to receive rapid effective diagnosis and treatment
Correspondence: Carlos V Serrano Jr than are men (Ayanian and Epstein 1991; Maynard et al 1996; Pope
Coronary Care Unit, Av. Dr. Enéas
Carvalho Aguiar, 44 – sala 12 – bloco 2,
et al 2000).
São Paulo - SP - 05403-900, Brazil Regarding the North American population, the Women’s Ischemic Syndrome
Tel +55 11 3069 5058
Evaluation (WISE) study workshop (Hayes et al 2004; Maseri 2004; Nabel et al 2004;
Fax +55 11 3088 3809
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

Vascular Health and Risk Management 2007:3(5)


Vascular Health and Risk Management 2006:2(4) 465–475 709
465
© 2006 Dove Medical Press Limited. All rights reserved
Author copy only
REVIEW

Coronary artery disease in women: a review


on prevention, pathophysiology, diagnosis, and
treatment
Leila Fernandes Araujo Abstract: Despite numerous studies on women’s cardiac health throughout the past decade, the
Alexandre de Matos Soeiro number of female deaths caused by cardiovascular disease still rises and remains the leading cause
Juliano Lara Fernandes of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular
Antônio Eduardo Pesaro disease, and more specifically coronary artery disease presentations in women, are different than
Carlos V Serrano Jr those in men. In addition, pathology and pathophysiology of the disease present significant
gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the
Heart Institute (InCor), University female population. The reason for this disparity is all steps for female cardiovascular disease
of São Paulo, School of Medicine,
Brazil evaluation, treatment and prevention are not well elucidated; and an area for future research. This
review brings together the most recent studies published in the field of coronary artery disease
in women and points out new directions for future investigation on some of the important issues.
Keywords: coronary artery disease, women, risk factors, prevention, diagnosis, treatment.

Introduction
The first female-specific recommendations for preventive cardiology were published in
1999 (Mosca et al 1999). Even though research in the treatment of cardiovascular disease
(CVD) had advanced in many areas, it remains the leading cause of death in women in
most parts of the world. Studies have shown that 500 thousand women die of CVD every
year in the United States, somewhat near one death every minute (American Heart
Association 2003). Such index exceeds not only the number of deaths in men, but also the
next seven causes of death in women combined, and more importantly, coronary artery
disease (CAD) is believed to be the major cause responsible for these deaths (American
Heart Association 2003). Over a quarter of a million deaths per year are attributed to CAD
alone in the United States (Merz et al 2004). Although already high, these figures are
expected to rise even more during the next decades, due to an increase of diabetes and
obesity, as well as the aging of the world population (Merz et al 2004).
Even though women have a higher frequency of chest pain/angina than men, the
incidence of obstructive CAD in the female population is lower when compared with
men with similar symptoms (Kenedy et al 1982; Diamond et al 1983; Merz et al 1999). In
addition, it would appear that young women with obstructive CAD have a worse
prognosis after acute myocardial infarction (AMI), whereas older women in similar
circumstances often present with larger number of comorbidities that adversely influence
the outcome, when compared to men (Coronado et al 1997). Women with acute coronary
syndromes (ACS) are also less likely to receive rapid effective diagnosis and treatment
Correspondence: Carlos V Serrano Jr than are men (Ayanian and Epstein 1991; Maynard et al 1996; Pope
Coronary Care Unit, Av. Dr. Enéas
Carvalho Aguiar, 44 – sala 12 – bloco 2,
et al 2000).
São Paulo - SP - 05403-900, Brazil Regarding the North American population, the Women’s Ischemic Syndrome
Tel +55 11 3069 5058
Evaluation (WISE) study workshop (Hayes et al 2004; Maseri 2004; Nabel et al 2004;
Fax +55 11 3088 3809
Email carlos.serrano@incor.usp.br Pepine et al 2004; Shaw et al 2004; Waters et al 2004) from the National Heart, Lung and

Vascular Health and Risk Management 2006:2(4) 465–475 465


© 2006 Dove Medical Press Limited. All rights reserved