ATHEROSCLEROSIS
By Dr. Lokhande Vijay V.
DEFINITION:
Atherosclerosis is defined by the WHO as a variable combination of changes of the
intima consisting of focal accumulation of lipids, complex carbohydrates, blood and constituents,
fibrous tissue and calcium deposits, combined with changes of the media. Atherosclerosis is thus
a patchy, nodular type of arteriosclerosis.
CLASSIFICATION: The lesions of atherosclerosis are commonly classified as:
1) Fatty streaks: It forms the earliest lesions of atherosclerosis. They may be reversible and
appear early in life, particularly in the aorta. They are characterised by accumulation of
lipid-filled smooth muscle cells, macrophages (foam cells) and fibrous tissues in focal areas
of the intima.
2) Fibrous plaques: These are elevated areas of intimal thickening and represent the most
characteristic lesion of atherosclerosis. They appear first in the abdominal aorta, coronary
and carotid arteries. They consist of a central core of extracellular lipid and necrotic cell
debris covered by a fibromuscular layer consisting of smooth muscle cells, macrophages
and collagen.
3) Complicated lesions: These are calcified fibrous plaques with various degrees of necrosis,
thrombosis and ulceration. These lesions commonly produce symptoms of ischaemia.
LOCALISATION:
a) Aorta (abdominal aorta) is involved earliest and is most severely affected.
b) Coronary artery: Lesions are often seen in the extramural portion in the proximal part and
in the main stem
c) Cerebral arterr: In the cerebral circulation the carotid system is more vulnerable than the
vertebrobasilar system. The proximal portion of the left carotid in the neck and the
bifurcation are sites of special predilection.
d) Atherosclerosis is more marked in the lower limbs compared to the upper limbs, especially
the femoral artery in the Hunter’s canal and in the popliteal artery just above the knee.
The internal mammary artery seems to be resistant to atherosclerosis. Lesions do not
develop here even when it is used as a graft for coronary artery bypass surgery. Atherosclerosis,
however, often develops in the saphenous vein when it is used as a graft.
AETIOLOGY:
Risks factors for atherosclerosis:
Non-modifiable Modifiable
Major Minor
Age • Hyperlipidaemia • Obesity
Sex • Diabetes mellitus • Physical inactivity
Heredity • Smoking • Psychosocial tensions
• Hypertension
• Diet
Hyperlipidaemia:
a) Hypercholesterolaemia is clearly a risk factor.
b) Low density lipoprotein (LDL) is a lipoprotein and it is most atherogenic.
c) Very low density lipoprotein (VLDL) is comparatively less atherogenic.
d) High density liproprotein (HDL) offers a protective effect and helps in removing
cholesterol from the arterial wall.
e) The ratio of LDL/HDL is a common way to assess the atherogenicity of hyperlipidemia. A
ratio of more than 4.5 is supposed to be atherogenic.
f) A minor increase of 1 mg/dl in HDL cholesterol produces a 2-4% decrease in the risk of
developing acute myocardial infarction (AMI).
g) In Indians (living in India or abroad), raised triglycerides with low HDL has been found to
be atherogenic.
1) Serum cholesterol: It is classified into three groups as follows
a) Desirable (less than 200 mg/dl)
b) Borderline (200 to 239 mg/dl): Patients with borderline cholesterol and no other risk
factor should be given dietary information and checked once a year.
c) High (more than 240 mg/dl): Those with high blood cholesterol should have lipoprotein
analysis and should be managed accordingly.
2) LDL cholesterol is also classified into three groups as follows
a) Desirable (less than 130 mg/dl)
b) Borderline high risk (130 – 160 mg/dl)
c) High risk (more than 160 mg/dl)
3) High Density Lipoprotein (HDL):
a) HDL cholesterol below 30 mg/dl is atherogenic.
b) In fact, low HDL cholesterol is a greater risk factor than high total or LDL cholesterol.
c) HDL cholesterol is decreased by androgens, beta blockers, cigarette smoking, obesity,
lack of exercise and hypertriglyceridaemia.
d) HDL cholesterol averages 25% higher in women than in men.
e) There is an inverse relationship between plasma triglycerides and HDL cholesterol.
4) Apolipoproteins:
1) In CAD, apolipoprotein A1 is decreased and apolipoprotein B is increased.
2) The ratio of apo B/apo A1 is a better index of atherogenicity than even the total
cholesterol and HDL cholesterol ratio.
3) Apolipoprotein analysis may predict CAD, even in normolipidaemic persons.
4) Lp (a) > 30 mg is abnormal and an independent risk factor for CAD.
Diabetes mellitus:
1) Diabetics are more prone to atherosclerotic disease such as CAD, cerebral stroke and
peripheral vascular disease.
2) Glycaemic control has a striking impact on the development of microvascular
complications like retinopathy, nephropathy and neuropathy.
3) Impact of glycaemic control on macrovascular disease (atherosclerosis) is less striking.
4) There is no clearly established that the direct effect of glucose and insulin on the arterial
wall, effect of circulating lipoproteins, abnormalities of blood clotting and fibrinolysis,
and even the influence of antidiabetic treatment itself
Smoking:
1) Smoking is a major risk factor for atherosclerosis.
2) The incidence of ischaemic heart disease is 3-5 times higher in smokers who smoke 20
cigarettes per day compared to non-smokers.
3) The incidence of sudden death is also higher in smokers.
4) Smoking decreases HDL cholesterol.
5) Women cigarette smokers are also at greater risk of developing CAD than non-smokers.
In those who smoke and also use oral contraceptives, the risk is increases many fold.
6) Continuation of smoking increases incidence of re-stenosis after percutaneous
transluminal coronary angioplasty and coronary artery bypass grafting.
Hypertension:
1) In the Framingham study, the incidence of CAD in middle-aged men with blood pressure
exceeding 160/95 mmHg was more than five times that in normotensive men.
2) With control of blood pressure, the incidence of cerebral stroke decreases, but the
incidence of AMI is not substantially altered.
Age: The risk for atherosclerosis increased progressively with age.
Diet: A diet rich in saturated fat and cholesterol is associated with increased incidence of
atherosclerosis.
Minor risk factors:
Obesity:
1) It is not an independent risk factor but is closely associated with hyperlipidaemia and
hypertension.
2) Physical inactivity is also believed to be associated with increased atherosclerosis.
3) Physical activity increases HDL level.
Emotional stress and anxiety: may also be important risk factors and increase the risk of
sudden death.
INVESTIGATIONS:
1) Angiography: It only visualises luminal narrowing and does not directly visualise the
atheromatous plaque.
2) Intravascular Ultrasonography (IVU): It directly visualises the atheromatous plaque and
also gives an idea about the contents of the plaque which is crucial in deciding what type of
catheter intervention is best suited for a given patient of atherosclerotic disease like
coronary artery disease (CAD). IVU is also useful in early diagnosis of dissection and in
judging the adequacy of catheter interventions, particularly in CAD.
Medical abravations and terminologies:
CAD = Coronary artery disease
Lp = Lipoprotein
LDL = Low density lipoprotein
VLDL = Very low density lipoprotein
HDL = High density liproprotein
AMI = acute myocardial infarction
