ISCHEMIC HEART DISEASE

ATHEROSCLEROSIS
Lecturer – prof. Yu.R. Kovalev
 GENERAL CONSIDERATIONS

IHD - clinical disorders are caused by

reduction in arterial blood supply to the
myocardium.
In the vast majority of cases the lesion of
the coronary arteries is atherosclerosis
 CLINICAL CLASSIFICATION OF IHD
1. Sudden coronary death
2. Angina pectoris
2.1. Stable angina pectoris
2.2. Unstable angina pectoris
2.3. Variant (Prinzmetal’s) angina
3. Acute myocardial infarction
4. Postinfarction or atherosclerotic cardiosclerosis
(ischemic cardiomyopathy)
5. Cardiac arrhythmias or conduction defects
6. Heart failure
7. Asymptomatic (silent) myocardial ischemia
DIAGRAMMATIC REPRESENTATION OF
CORONARY ANATOMY
• significant disease
was defined as
stenosis of 50% or
greater in the left main
coronary artery or
more than 70% in
other vessels and
major branches
 Coronary anatomy
The right and left coronary arteries arise from the
root of the aorta as its first branches. The left
coronary artery divides into two major branches—
the left circumflex and left anterior descending.
Branches of the left descending branch supply the
free wall of the left ventricle and a major portion of
the interventricular septum. The left circumflex
artery supplies the left atrium and parts of the
posterior and lateral walls of the left ventricle. In
45 per cent of cases this artery supplies the S-A
node as well.
 Coronary anatomy
The right coronary artery supplies the right
ventricle, a major portion of the
diaphragmatic surface of the left ventricle,
the A-V node (in 90 per cent) and the S-A
node (in 55 per cent). Venous blood from
the heart is drained into the right atrium
through the coronary sinus, Thebesian
veins and the anterior cardiac veins.
 Coronary anatomy
Around 4-6 per cent of the cardiac output flows into
the coronary arteries in health. The coronary
arteries run on the epicardial surface and their
branches penetrate to supply the myocardium. The
outer two-thirds portion is supplied by the
epicardial branches and the inner one-third is
supplied by perforating branches which form
subendocardial ramifications. The left ventricular
myocardium receives blood almost exclusively
during diastole whereas the right ventricular
myocardium receives blood during both phases of
the cardiac cycle.
 Metabolism of cardiac muscle
Metabolism of cardiac muscle is aerobic. The
myocardium extracts 70 per cent of the oxygen
supplied to it in arterial blood. If the oxygen
supply is interrupted for over two minutes, the
myocardium becomes ischemic and the
mechanical activity ceases totally. Ischemia may
result from organic narrowing of the coronary
arteries or spasm or both. Factors which further
reduce coronary blood flow are extreme
tachycardias (due to reduction of diastolic
interval), hypertension, elevation of
intraventricular pressure as in aortic and
pulmonary stenosis, and cardiomegaly. Ischemia
to the myocardium causes the characteristic pain.
 ETIOLOGY OF IHD
1. Coronary atherosclerosis is the most
frequent cause of IHD.
2. Non-atheromatous coronary artery
diseases (Less than 1% of causes)
• Arteritis: Polyarteritis nodosa, nonspecific
arteritis, syphilitic aortitis, systemic lupus
erythematosus, thromboangitis obliterans, etc.
• Thickening of coronary arteries:
mucopolysaccharidoses, amyloidosis.
• Spasm of coronary arteries generally
supervenes on diseased arteries but
sometimes no pathological lesion may be
detectable
 ETIOLOGY OF IHD
• Dissecting aneurysm of the aorta, dissection of
the coronary arteries.

• Embolism: Infective endocarditis, emboli from

the left atrium or left ventricle, left atrial myxoma
or paradoxical embolism may affect the coronary
arteries.

• Congenital anomalies: Anomalous origin of the

left coronary artery from the pulmonary artery,
coronary arteriovenous fistula, aneurysms of the
coronary arte-ries.
 ETIOLOGY OF IHD
• Trauma to the coronary arteries:
Penetrating wounds, injury during
pericardiocentesis.

• Imbalance between oxygen demand and

blood supply: Severe aortic stenosis,
aortic regurgitation, prolonged
hypotension, severe anaemia,
thyrotoxicosis, gross tachycardia, etc
NON-MODIFIABLE RISK FACTORS
•Age
•Male gender
Ischemic heart disease accounts for 13—24 per cent of
the total cardiac morbidity in many countries. Men
suffer 9 times more frequently than premenopausal
women, but after menopause the risk of coronary
atherosclerosis rapidly increases to catch up with that of
men over a period of several years.
•Genetic predisposition
Genetic predisposition to atheroma is revealed by a
positive family history of ischemic heart disease (sudden
deaths, myocardial infarction, or angina) or
cerebrovascuJar accidents occurring at relatively
younger ages (till 50 -55 years) among close relatives.
NON-MODIFIABLE RISK FACTORS
•Personality factors
High strung aggressive and competitive
individuals (type A) are more prone to develop
myocardial infarction than the more relaxed type
of personality (type B).
 MODIFIABLE RISK FACTORS
•Hyperlipidemia
•Cigarette smoking
•Hypertension
•Diabetes mellitus
•Low physical activity
•Postmenopausal state
•High lp(a) level
(homology with plasminogen)
•Hyperhomocysteinemia
(it may inhibit fibrinolisis)
Hyperlipidemia: The risk of coronary atherosclerosis is
directly related to elevation of serum cholesterol.
Increase in levels above 5 mmol/L is associated with
increasing risk. Lipids circulate in blood in the form of
lipoproteins. Based on electrophoretic pattern and density
gradient they can be classified into alpha-lipoproteins
(high density HDL), beta lipoproteins (low density LDL)
and pre-beta lipoproteins (very low density VLDL). Rise in
level of HDL is protective against atheroma whereas
increase in LDL and VLDL favour atherogenesis. Many
types of hyperlipidemias are genetically determined, but
by proper dietary modification, exercise, and drug therapy
the serum levels can be lowered and this risk can be
brought down to some extent.
 MODIFIABLE RISK FACTOR
•Hyperlipidemia
TYPES OF DYSLIPOPROTEINEMIA
according to Fredrickson
TYPE Plasma changes Plasma changes
in lipoproteins in lipids
Hyperlipo-
proteinemias
IIA LDL ↑ Cholesterol ↑

IIB LDL and VLDL↑ Cholesterol and

Triglycerides↑
IV VLDL↑ Triglycerides↑
Hypoalfa- HDL ↓ Cholesterol of
holesterolemia HDL (α -chol.)↓
 NORMAL VALUES OF PLASMA
LIPIDS
Total Cholesterol (TCh) – less than 5,2 mmol/l (200
mg/dl)
Tryglycerides – less than 1,6 mmol/l (140 mg/dl)
Alfa-Cholesterol (Ch HDL) – more than 1,2 mmol/l
(45 mg/dl)
Coefficient of atherogenity (CA) – 3,5 – 3,0 r.u.

TCh – Ch HDL
CA = --------------------- (r.u.)
Ch HDL
PERIPHERICAL SIGNS OF ATHEROSCLEROSIS

Xanthomas on the hand, patient 12 y. old

 PERIPHERICAL SIGNS OF
ATHEROSCLEROSIS

Eruptive xanthomas, a man 33 y. old

PERIPHERICAL SIGNS OF ATHEROSCLEROSIS

Palpebrarum xanthomas, arcus senilis, patient, 47 y.

old
 PERIPHERICAL SIGNS OF
ATHEROSCLEROSIS

Tuberosum xanthomas, patient, 47 y. old

ATHEROSCLEROSIS OF AORTA

2 – Lipoid infiltration
3 – Fibrotic changes, mild calcinosis
4 –Severe calcinosis
5 – Ulcers of vessel wall
ATHEROSCLEROTIC PLAQUE STRUCTURE
Cholesterol
Smooth muscle cells crystals

Collagen Foam cells

fibers

DEVELOPMENT OF ATHEROSCLEROSIS
•Endothelial injury
•Proliferation of smooth muscle cells
•Synthesis of connective tissue matrix
•Focal accumulation of monocytes/macrophages (foam cells)
•Lymphocyte infiltration
•Intracellular and extracellular lipid accumulation
•Stenotic lesions
Atheroma commonly affects the proximal
portions of the epicardial vessels. This
may lead to single or multiple
obstructions. Most frequently affected
vessel is the anterior descending branch
of the left coronary artery. In left
circumflex branch and main left artery
plaques are also often located. Right
coronary artery is affected more rarely.
MORE FREQUENTLY AFFECTED
VESSELS
In atherosclerosis, focal fibrofatty
elevations (plaques) develop in the intimal
and subintimal regions resulting in
progressive narrowing of the lumen.
Severe complications may develop. These
include hemorrhage into the atheroma,
ulceration of subintimal surface,
embolisation of the atheromatous plaque,
thrombosis starting at the narrowed
portions of the arteries, and calcification.
LESION PROGRESSION IN A FIBROFATTY
PLAQUE

A – adventitia,
FC – fibrous cap,
C – calsification
F – obvious fissure
MP – myofibroblastic
proliferation
Progressive occlusion of the lumen of the
coronary arteries may remain totally
asymptomatic till the circulation is
considerably diminished. In general the
development of complications gives rise to
one of the clinically detectable syndromes.
 STABLE ANGINA PECTORIS
The term "angina pectoris" is used to denote
the pain or discomfort produced by reversible
myocaidial ischemia brought on by exertion or
emotion and relieved by rest.
Ischemic cardiac pain starts and increases
with exertion or emotion and forces the patient to
stop activity. With rest the pain completely subsides
within a few minutes.
At times the manifestation may be only undue
dyspnoea or vague chest discomfort rather than the
clearcut pain.
 STABLE ANGINA PECTORIS
Stenosis of coronary lumen consists 75% or more

stenosis stenosis

Myocardial perfusion in Ischemia appears during

rest is enough physical exertion
 STABLE ANGINA PECTORIS
•Precordial or anterior chest
Angina attack discomfort accompanies physical
activity or emotion stress
•Discomfort is described as a true
pain or as a heaviness, squeezing,
tightness, pressure or aching.
•Localization is sternal or substernal
•Radiation is to the left shoulder or
arm
•Chest pain abates up to 15 – 20
minutes, when the aggravating
activity is stopped
•Sublingual nitrates relief attack in 1
to 3 minutes
GESTURES OF PATIENT WITH ANGINA
PECTORIS
FUNCTIONAL CLASSIFICATION
OF ANGINA PECTORIS
I. Ordinary physical activity, such as walking and
climbing stairs, does not cause angina. Angina
results from strenuous or rapid or prolonged
exertion at work or recreation.
II. Slight limitation of ordinary activity. Walking or
climbing stairs rapidly, walking uphill, walking or
stair climbing after meals, in cold, in wind, or
when under emotional stress, or only during the
few hours after awakening, Walking more than
two blocks on the level and climbing more than
one flight of ordinary stairs at a normal pace and
under normal conditions.
FUNCTIONAL CLASSIFICATION
OF ANGINA PECTORIS
III. Marked limitations of ordinary physical
activity. Walking one to two blocks on the level
and climb-ing more than one flight under normal
conditions.
IV. Inability to carry on any physical activity
without discomfort—anginal syndrome may be
present at rest.
 Diagnosis
Angina pectoris should be diagnosed by
history. This is confirmed by ECG done
during or soon following exercise. The
depression of the S—T segment and
change in the T-wave are diagnostic of
angina. The whole procedure has been
quantitated by the treadmill test, in which
the ECG response to graded exercise can
be recorded. The pattern of ECG
abnormality has been correlated with the
severity of coronary artery occlusion.
 ECG CHANGES DURING ANGINA
PECTORIS ATTACK
•Horizontal or
downsloping ST
depression
•J-point depression
are 1 mm or greater
•ST slope is within the
J range of 7 to 10 mm

Rest Treadmill test

 Diagnosis
Cardiac enzymes are not elevated in
angina. Radioisotopic studies reveal
myocardial ische-mia. Radioisotope (Tc99
or Tl201) is given by intravenous way at
the time of treadmill test. Black arrows
show ischemic areas. Second infusion of
radioisotope in rest reveals the
reversibility of changes
 RADIOISOTOPIC STUDIES
Radioisotope (Tc99 or Tl201 ) is given by intravenous way at the
time of treadmill test. Black arrows show ischemic areas.
Second infusion of radioisotope in rest reveals the reversibility of
changes

Treadmill test Rest

 Management
During the acute attack, cessation of
activity and sublingual administration of
nitroglycerine tab or spray give immediate
relief. Nitrates lower the peripheral
resistance by vasodilatation, reduce
venous return and lower the afterload.
Nitroglycerine tablets deteriorate in
sunlight and, therefore, they have to be
kept in coloured containers.
 Management
Other drugs belonging to this class are
isosorbide dinitrate or mononitrate.
 DRUGS COMMONLY USED FOR
ANGINA PECTORIS
Nitrates Usual doses Side effects
Sublingual 0,3 – 0,6 mg Flushing, headache
nitroglycerin
Isosorbite dinitrate
Oral 10 – 60 mg q 8 h As above
Sublingual 2,5 – 10 mg q 4 – 6 h Tolerance after 24 h
Isosorbit-5-
mononitrate
Oral 20 – 30 mg bid As above
Oral SR 60 – 120 mg one daily As above
 Management

Selective beta-blockers reduce myocardial

work and oxygen requirement, by reducing
heart rate, blood pressure, and myocardial
contractility. They can be given on a long-
term basis to prevent angina. A resting
heart rate of 50-60/min. is ideal.
 DRUGS COMMONLY USED FOR
ANGINA PECTORIS
Beta blockers Usual doses Side effects
Propranolol 20 – 40 mg qid Depression,
Metoprolol 25 – 200 mg bid constipation,
Atenolol 50 – 150 mg one daily bronchospasm,
bradycardia, heart
failure
 Management

Calcium channel blocking drugs like

verapamil and nifedipine are very
useful in preventing angina.
 DRUGS COMMONLY USED FOR
ANGNA PECTORIS
Calcium channel Usual doses Side effects
blocking drugs
Nifedipine-retard 30 – 90 mg daily Hypotension,
flushing, edema,
worsening angina
Diltiazem SR 60 – 120 mg bid Constipation, AV-
conduction block,
worsening heart
failure
Verapamil SR 180 – 240 mg daily As above
Amlodipine 5 – 10 mg daily Edema
PERCUTANEOUS TRANSLUMINAL
CORONARY ANGIOPLASTY
Stenosis zone

Conductor

Inflated balloon

Reperfusion
INTRACORONARY STENTS
The problem of PTCA is
restenosis.
Stenting may prevents
restenosis processes.
The restenosis is much
more rare if stents are
covered by cytostatics.
CORONARY ARTERY BYPASS GRAFTING

Patients with stenosis

Shunt to the
circumflex of the left main
branch of the
left coronary
coronary artery and/or
artery those with three
vessel CAD are best
treated with CABG
 UNSTABLE ANGINA PECTORIS
The following three patient groups may be
said to have unstable angina pectoris:
(1)patients with new onset (<2 months) angina that
is severe and/or frequent (≥ 3 episodes per day);
(2) patients with accelerating angina, i.e., those with
chronic stable angina who develop angina that is
distinctly more frequent, severe, prolonged, or
precipitated by less exertion than previously;
(3)those with angina at rest.
 UNSTABLE ANGINA PECTORIS
The duration of the illness is less than
two months. The general nature of the pain is
similar to that of stable angina.
If it supervenes on a patient with stable
angina, the frequency and duration of attacks
increase, the sites of radiation change and
exercise tolerance progressively falls.
The response to nitroglycerine is
considerably less.
Anginal attacks occur at rest.
 UNSTABLE ANGINA PECTORIS
Several mechanisms for unstable angina
have been described:
(1) a nonocclusive thrombus—often a platelet
plug—overlying a fissured atherosclerotic
plaque;
(2) dynamic obstruction—either spasm of an
epicardial coronary artery, as in Prinzmetal's
variant angina, or abnor-mal vasoconstriction of
the coronary microcirculation, as in
microvascular angina;
(3) severe, organic luminal narrowing, as in
restenosis following a PCI;
HIGH SHORT-TERM RISK OF DEATH OR
NONFATAL MYOCARDIAL INFARCTION
•Prolonged >20 min rest pain
•Pulmonary edema
•Angina in rest with dynamic ST changes ≥
1mm
•Angina with new or worsening MR murmur
•Angina with new/worsening rales
•Angina with hypotension
 TREATMENT OF UNSTABLE ANGINA

The patient is admitted to the hospital, placed

at rest, sedated, and reassured. In all
instances, concomitant conditions that can
intensify ischemia, such as tachycardia,
hypertension, diabetes mellitus, cardiomegaly,
heart failure, arrhythmias, thyrotoxicosis, and
any acute febrile illness, should be sought and
vigorously treated.
 TREATMENT OF UNSTABLE ANGINA
Drugs Usual doses Side effects
Nitroglycerin 0,3 – 0,4 mg every 5 Flushing,
Sublingual min up to 1,2 mg Headache,
Intravenous 5 – 75 mkg/min Hypotension
Beta-blocker AV-block
Metoprolol 5 mg every 15 min Bradycardia,
i.v. up to 15 mg Hypotension,
Heart failure,
Bronchospasm
Aspirin 160 - 320 mg daily Active bleeding

Heparin 80 U/kg bolus than Active bleeding

18 U/kg/h during 2 –
3 days
 ACUTE MANAGEMENT IN RELATION
TO HIGH RISK OF MYOCARDIAL
INFARCTION OR DEATH
• Emergency room & ECG monitoring ≥ 48 hr.
• Intravenous narcotics: Morphine sulfate 2 – 5 mg once
in a case of persistent pain
• Anti-ischemic: i.v. nitrates and β-blockers
• Antitrombotic/antiplatelet: aspirin (clopidogrel), oral
daily; unfractionated heparin bolus i.v. ≥ 48 hr. low
molecular weight heparins and IIb/IIIa receptors
inhibitors may be used
• Revascularization should be performed
 TREATMENT OF UNSTABLE ANGINA
The majority of patients (approximately 80%) improve
with rest and medical treatment over a 48-h period. If
angina at rest and/or ECG evidence of ischemia
persist despite 24 to 48 h of the comprehensive
treatment, then cardiac catheterization and coronary
arteriography should be performed in patients with no
obvious contraindications for revascularization. PCI
or CABG should be considered to relieve symptoms
and myocardial ischemia and as a means of
preventing myocardial damage.
 VARIANT ANGINA
This relatively uncommon form of unstable
angina is characterized by recurrent, prolonged
attacks of severe ischemia, caused by episodic
focal spasm an epicardial coronary artery.
Approximately threefourths of patient with
Prinzmetal's angina exhibit a mild or moderately
severe fixed obstruction (with a luminal diameter
50 to 70% of normal) within 1 cm of the site of
spasm. Patients with this condition are often
smokers and are younger than patients with
unstable angina secondary to coronary
atherosclerosis.
 VARIANT ANGINA
Ischemic pain usually occurs at rest, sometimes
awakens the patient from sleep, and is characterized
by multilead ST-segment elevation. The diagnosis
may be confirmed by detecting transient spasm
occurring spontaneously or following a provocative
stimulus (intracoronary acetylcholine,
hyperventilation) on coronary arteriography. While
long-term survival is excellent, complications include
episodes of disabling pain, myocardial infarction,
serious ventricular arrhythmias, atrioventricular block,
and, rarely, sudden death.
 VARIANT ANGINA
Spasm induced form of unstable angina
3/4 of patients has atherosclerotic Lumen may have only 1% of
obstruction with a luminal normal during attack
diameter 50 – 70% of normal

• Pain occurs at rest, sometimes awakes the patients from

sleep
•ECG – S-T segment is elevated
 TREATMENT OF VARIANT ANGINA
The acute attack
•Sublingual nitroglycerin
•Intravenous infusion of nitroglycerin
•Short-acting nifedipine (10 – 30 mg)

Chronic management
•Long acting nitrates
•Long acting calcium antagonists
•Selective α -adrenoblockers may be useful
•In patients with atherosclerotic stenosis -
revascularization
 SILENT ISCHEMIA
This is not uncommon even in apparently
normal individuals. Routine stress testing
may bring out the abnormality. Such cases
may develop acute myocardial infarction or
die suddenly as a result of ventricular
fibrillation or cardiac arrest.
Significant abnormalities in the treadmill
test are indications for coronary
arteriography. Occlusion of the left main
coronary artery or all the three vessels is
an indication for early bypass surgery.
 PREVENTION OF IHD

•Proper dietary manipulation to avoid high

intake of saturated fats, and overnutrition
•Avoidance of smoking;
•Regular exercises;
•Correction of hyperlipidemia
•Regular medical check up.
 HYPOLIPIDAEMIC THERAPY
Group of drug Mechanism of Therapeutic Adverse effects
action effect
Statins Inhibit the rate- Reduction of Derangement
Simvastatin limiting step of Ch LDL (30%) of liver
Pravastatin chlesterol Modest biochemistry,
synthesis lowering of diarrhoea,
Fluvastatin
(HMG-CoA triglycerides myositis
Atorvastatin
reductase) Tiny effect on
Ch HDL

Cholesterol- Inhibition of gut Reduction of Diarrhoea,

absorbtion absorbtion of CH LDL and abdominal
inhibitors cholesterol triglycerides discomfort
Ezetimibe from food and (10-15%)
from bile (not Increasing of
fully understood) CH HDL (5%)
 HYPOLIPIDAEMIC THERAPY
Group of drug Mechanism of Therapeutic Adverse effects
action effect

Cholesterol- Bind bile acids 8-15% Gastrointestinal

binding resins in the gut reduction in side effects
Colestyramine preventing LDL. Little or predominate.
enterohepatic no effect on
Colestipol
circulation. HDL
Liver makes cholesterol. 5-
more bile acids 15% rise in
from triglyceride
cholesterol. concentration
 HYPOLIPIDAEMIC THERAPY
Group of Mechanism of Therapeutic effect Adverse
drug action effects

Fibric acids Complex: Reduction of Ch Myositis,

derivatives Limit hepatic LDL (10 -15%), nausea,
Gemfibrozil triglycerides triglycerides (25 – malaise,
synthesis 30 %) impotence
Bezafibrate
Fenofibrate Promote action of Increasing of Ch
lipoproteins HDL (up to 50%)
Ciprofibrate
lipase a.o.
 HYPOLIPIDAEMIC THERAPY
Group of drug Mechanism of Therapeutic Adverse effects
action effect

Nicotinic acid Unclear Reduction of Ch Headache

LDL (5 -10%), flushing,
triglycerides (15 dizziness,
– 20 %) nausea,
Increasing of Ch malaise, itching,
HDL (10 - 20%) abnormal liver
biochemistry,
hyperglycemia,
hyperuricaemia,
peptic ulcers,
hyperpigmentati
on