Coronary heart disease

Atherosclerosis
- The commonest
arterial disease
characterized by
formation of fibro
fatty plaques,
formed of a deeper
soft part and a hard
sclerotic fibrous cap
Atherosclerosis
Epidemiology
a. Most common cause of morbidity caused
by vascular disease.

b. Highest incidence in Finland, Western

Europe, USA and Canada.

c. Increased incidence with advanced age.

d. More in males than females up to the

age of menopause.
 Risk factors

- Constitutional risk factors.

- Hard risk factors

- Soft risk factors

Risk factors
Nonmodifiable:
Age…The number and severity of
atheromatous lesions increase with
age.
Sex…More common in males than
females up to the age of 55 years.
Estrogen has a protective effect ??
Familial predisposition…Familial
hyperlipidemia (hypercholestrolemia)
is associated with increased risk of
atherosclerosis.
 Risk factors
Modifiable:
- Hyperlipidemia…Increased level of
cholesterol and LDL is associated with
increased risk of atherosclerosis.
On the contrary, HDL has a protective
effect against atherosclerosis.
- Hypertension
- Diabetes mellitus…due to associated
hyperlipidemia
- Cigarette smoking
 Risk factors
Modifiable:
- Exercise… Reduces the incidence of
atherosclerosis and death from
ischemic heart diseases
- Overweight….Atherogenic diet high in
animal saturated fatty acids and
cholesterol.
. High complex sugars in diet.
. Low vegetables and fish.
- Stress and personality…Personality A
Pathogenesis of Atherosclerosis
Reaction to injury formulation
Injury (or dysfunction) of endothelium
leads to…
Entry of monocytes and lipids to
subendothelim.
T cells located in the arterial wall
produce cytokines such as TNF, IL-6 and
IFN-γ that stimulate endothelial cells
and activate macrophages.
Platelet adhesion and aggregation.
Pathogenesis of Atherosclerosis
Release of mitogenic factors from
platelets and
macrophages…..proliferation and
migration of smooth muscle fibers.
Monocytes and smooth muscle cells
engulf lipid and cause lipid deposition
into the lesion.
At later stages, macrophages secrete
metalloproteinases that digest collagen
at the fibrous cap causing weakness and
rupture of the plaque.
Pathogenesis of Atherosclerosis
Pathology of atherosclerosis
Sites….
* Aorta, especially descending
* Coronaries and cerebrals
* Femoral , renal, superior mesenteric
and internal carotids.
Grossly….
- Multiple irregular patches more around
ostea of branches.
- Color ranges from yellow to white
according to relative amount of fat and
fibrous tissue.
- Covered by glistening intima (if not
complicated)
 Pathology of atherosclerosis

• The plaques are formed of

• 1- Central core of cholesterol and cholesterol
esters, lipid laden macrophages (foam cells),
necrotic debris and calcification.
2- Subendothelial fibrous cap formed of
proliferated smooth muscle cells, foam cells
and extra cellular matrix
Complications of atherosclerosis
1- Narrowing of vascular lumen…chronic
ischemia.
2- Superimposed thrombosis…acute
ischemia.
3- Ulceration with liberation of fatty
core … acute ischemia, fat emboli, DIC.
4- Pressure atrophy of the media with
fibrosis….weakening of the wall ….
Aneurysmal dilatation.
5- Dystrophic calcification.
Complicated atheromas
Ischemic heart disease (IHD)

Is a group of closely related

syndromes resulting from
myocardial ischemia with
imbalance between the
supply (perfusion) and
demand of the heart for
oxygenated blood.
IHD
*Ischemia is not only insufficiency
of oxygen, but also reduced
availability of nutrient substrates
and inadequate removal of
metabolites
*In more than 90% of cases, the
cause of ischemia is reduction in
coronary blood flow due to
atherosclerotic coronary arterial
obstruction .
Clinical manifestations of IHD
 Myocardial infarction: the most
important form of IHD, in which the
duration and severity of ischemia is
sufficient to cause death of heart
muscle
 Angina pectoris: in which the
ischemia is less severe and does not
cause death of cardiac muscle .
 Chronic IHD with heart failure
 Sudden cardiac death
Pathogenesis of IHD
 Acute Change on top of atheromatous
Plaque
Disruption, Thrombosis, vascular spasm
 Coronary Thrombosis
*luminal obstruction by thrombosis is
usually incomplete (mural thrombus).
* thrombus superimposed on partially
stenotic plaque converts it to a total
occlusion.
Pathogenesis of IHD
Vasoconstriction (vasospasm)
Vasoconstriction compromises lumen, and, by
increasing mechanical forces, can potentiate
plaque disruption. Vasoconstriction at sites
of atheroma is stimulated by:
(1) circulating adrenergic agonists.
(2) locally released platelet contents.
(3) Imbalance between endothelial cell
relaxing factors and contracting factors
(e.g., endothelin) due to atheroma-
associated endothelial dysfunction.
(4) Mediators released from perivascular
inflammatory cells.
Angina Pectoris
Paroxysmal and usually recurrent attacks
of substernal or precardial chest
discomfort (variously described as
constricting, squeezing, choking, or
knifelike) caused by transient (15
seconds to 15 minutes) myocardial
ischemia that falls short of inducing the
cellular necrosis that defines infarction .
Angina Pectoris

There are three overlapping patterns of

angina pectoris:
(1) Stable or typical angina.
(2) Prinzmetal or variant angina.
(3) Unstable or crescendo angina.
Angina Pectoris

They are caused by varying combinations

of increased myocardial demand and
decreased myocardial perfusion, owing
to fixed stenosing plaques, disrupted
plaques, vasospasm, thrombosis, platelet
aggregation, and embolization.
 Stable angina
The most common form (typical) appears
to be caused by the reduction of
coronary perfusion to a critical level by
chronic stenosing coronary
atherosclerosis.
The attacks are provoked by physical
activity, emotional excitement, or any
other cause of increased cardiac
workload.
Typical angina pectoris is usually relieved
by rest (decrease demand) or
nitroglycerin, a strong vasodilator.
Prinzmetal angina

An uncommon pattern of episodic angina

occurs at rest and is due to coronary
artery spasm. Although individuals
with this form of angina may well have
significant coronary atherosclerosis,
the anginal attacks are unrelated to
physical activity, heart rate, or blood
pressure.
Unstable angina
Progressively increasing pain frequency,
is precipitated with progressively less
effort, often occurs at rest, and tends
to be of more prolonged duration .
It is induced by disruption of an
atherosclerotic plaque with
superimposed partial (mural)
thrombosis and possibly embolization or
vasospasm or both.
It is referred to as preinfarction angina
and in the spectrum of IHD
Myocardial Infarction
1-Transmural Infarction
Most myocardial infarcts are
transmural ,in which the ischemic
necrosis involves the full or nearly full
thickness of the ventricular wall in the
distribution of a single coronary artery.
This pattern of infarction is usually
associated with coronary
atherosclerosis, acute plaque change,
and superimposed thrombosis
Myocardial Infarction
2- Subendocardial (nontransmural)
infarct:
It constitutes an area of ischemic
necrosis limited to the inner one third
or at most one half of the ventricular
wall.
It occurs as a result of a plaque
disruption followed by coronary
thrombus that becomes lysed before
myocardial necrosis extends across the
major thickness of the wall
(MI) Incidence and Risk Factors
MI occurs at any age, but the frequency
rises progressively with increasing age
and when predispositions to
atherosclerosis are present ,such as
 Hypertension,
 Cigarette smoking,
 Diabetes mellitus,
 Genetic hypercholesterolemia,
 Causes of hyperlipoproteinemia.
Nearly 10% of myocardial infarcts occur
in people under age 40, and 45% occur
in people under age 65.
(MI) Incidence and Risk Factors
Blacks and whites are equally affected.
Throughout life, men are at significantly
greater risk of MI than women with
progressively declines with advancing
age
IHD is the overwhelming cause of death
in elderly women. Moreover, recent
epidemiologic evidence suggests that
postmenopausal hormone replacement
therapy does not protect women against
MI
(MI) Morphology, Gross
Before 6-12 hours, MI is inapparant
only by histochemical techniques.
By 18-24 hours, infarcted tissue
appear pale to cyanotic area.
In the 1st week, lesions are
progressively more define, yellow and
soft.
7-10th day, hyperaemic granulation
tissue fill the are
6th week, white fibrous scar.
(MI) Morphology, Microscopic
Within 1hour,there is intracellular
edema. Myocyte at the pariphery
becomes wavy and contracted.
By 12-72 hours, dead myocyte becomes
hyperesinophilic with loss of nuclei
(coagulative necrosis).
From 3 -7 days, dead myocyte are
digested by invading macrophages.
7-10th day, granulation tissue replaces
necrotic tissue leading to dense fibrous
scar .
Acute MI
Acute MI
Acute MI
Acute MI

Neutrophilic infiltrate along with areas of

necrosis, diffuse interstitial edema and pale
myocytes with fading nuclei and decreased
striations
Old MI
Old MI
Old MI
MI with mural thrombus
(MI) severity
The location and severity of development of
myocardial infarction depends on:
 The size of the vascular bed perfused by
the obstructed vessels
 The duration of the occlusion
 The metabolic/oxygen needs of the
myocardium at risk
 The extent of collateral blood vessels
 The presence, site and severity of
coronary arterial spasm
 Other factors, such as alterations in blood
pressure, heart rate, and cardiac rhythm.
(MI) Clinical Features
Typical symptoms, biochemical evidence,
and by the ECG pattern
Laboratory evaluation is based on
measuring the blood levels of intracellular
macromolecules that leak out of fatally
injured myocardial cells through damaged
cell membranes; include myoglobin, cardiac
troponins T and I, creatine kinase (CK),
lactate dehydrogenase, and many others.
they do not reflect its mechanism Troponin
levels remain elevated for 7 to 10 days after
the acute event.
(MI) Complications
o Arrhythmias
o Myocardial rupture
o Pericarditis
o Right ventricular infarction
o Infarct extension
o Infarct expansion
o Mural thrombus
o Ventricular aneurysm
o Papillary muscle dysfunction
o Progressive late heart failure
o Contractile dysfunction
Chronic Ischemic Heart Disease
(CIHD)
Progressive heart failure as a
consequence of ischemic myocardial
damage.
The term ischemic cardiomyopathy is
often used by clinicians to describe
CIHD.
In most instances, there has been
prior MI and sometimes previous
coronary arterial bypass graft surgery
or other interventions.
Chronic Ischemic Heart Disease
(CIHD)
Morphology:
Hearts are usually enlarged and heavy,
secondary to left ventricular hypertrophy and
dilation.
Discrete, gray-white scars of healed infarcts
are usually present. The mural endocardium is
generally normal except for some superficial,
patchy, fibrous thickenings, although mural
thrombi may be present.
The major microscopic findings include
myocardial hypertrophy, diffuse subendocardial
vacuolization, and scars of previously healed
infarcts.
Sudden Cardiac Death
unexpected death from cardiac causes
early after symptom onset (usually within 1
hour) or without the onset of symptoms.
In many adults, SCD is a complication and
often the first clinical manifestation of
IHD.
Increased cardiac mass is an independent
risk factor for cardiac death; thus, some
young patients who die suddenly, including
athletes, have hypertensive hypertrophy or
unexplained increased cardiac mass as the
only finding.
Sudden Cardiac Death
With decreasing age of the victim, the following
nonatherosclerotic causes of SCD become
increasingly probable:
Congenital structural or coronary arterial
abnormalities
Aortic valve stenosis
Mitral valve prolapse
Myocarditis
Dilated or hypertrophic cardiomyopathy
Pulmonary hypertension
Hereditary or acquired abnormalities of the
cardiac conduction system
Isolated hypertrophy, hypertensive or unknown.
Sudden Cardiac Death
The ultimate mechanism of SCD is most
often a lethal arrhythmia (e.g., asystole,
ventricular fibrillation) triggered by
electrical irritability of myocardium
induced by ischemia.
The prognosis of patients risky for
SCD, is markedly improved by
implantation of an automatic cardioverter
defibrillator, which senses and
electrically counteracts an episode of
ventricular fibrillation.
Thank
you