Page 256 - Concise Pathology for Exam Preparation ( PDFDrive )

10 Blood Vessels 241

Risk Factors

1. Major risk factors
(a) Constitutional (nonmodifiable)
(i) Age: Early lesions of atherosclerosis may be present in childhood, but clini-
cally significant lesions are found with increasing age.
(ii) Sex: Males are more commonly affected than females; atherosclerosis is uncom-
mon in premenopausal women. Increased incidence in postmenopausal women
was thought to be due to falling oestrogen levels; however, oestrogen replacement
therapy in older women has not been found to decrease the cardiovascular risk.
(iii) Genetic factors: Hereditary genetic derangements of lipoprotein metabolism,
which predispose the individual to high blood lipid level like familial hyper-
cholesterolaemia have been implicated.
(iv) Familial and racial factors: The established predisposition to ischaemic heart
disease is multifactorial in origin and is related to the presence of other risk
factors like diabetes and hypertension which show familial clustering. Blacks
have less severe atherosclerosis than whites.
(b) Acquired (potentially modifiable)
(i) Hyperlipidaemia:
• Major classes of lipoproteins are chylomicrons, VLDL (very low density lipo-
proteins), low density lipoproteins (LDL) and high density lipoproteins (HDL).
• LDL delivers cholesterol to peripheral tissues (bad cholesterol) and HDL
removes cholesterol from the tissues to deliver it to the liver to finally be
excreted in the bile (good cholesterol).
• Diets containing large quantities of saturated fats raise the plasma choles-
terol levels. Also, transfats which form due to artificial hydrogenation of
polyunsaturated oils (as in baking) are immensely harmful.
• Diets rich in polyunsaturated fats and omega-3-fatty acids lower the plasma
cholesterol levels.
• Most evidence implicates hypercholesterolaemia:
• Atherosclerotic plaques contain cholesterol and cholesterol esters.
• Individuals with hypercholesterolaemia, eg, patients of diabetes melli-
tus, myxoedema and nephrotic syndrome, have increased risk of devel-
oping atherosclerosis.
• Dietary regulation and cholesterol-reducing drugs have beneficial effects.
Note: Main lipids in blood are cholesterol (normal 140–200 mg/dL; bor-
derline, 240 mg/dL) and triglycerides (normal ,160 mg/dL). Elevation of
serum cholesterol .260 mg/dL in men and women causes three times
higher risk of heart disease.
(ii) Hypertension: Major risk factor at all ages
(iii) Diabetes mellitus: Atherosclerosis manifests faster in both Types I and II diabetes
mellitus
(iv) Smoking: Men who smoke a pack of cigarettes a day are 3–5 times more likely
to die of IHD (ischaemic heart disease) than nonsmokers
2. Minor risk factors
(a) Inflammation is an integral part of evolution of atherosclerosis and is very closely
linked to its development. C-reactive protein (CRP), a marker of inflammation, has
been found to be one of the most sensitive predictors of ischaemic heart disease.
(b) Obesity: Abdominal/central obesity has been found to be an important risk factor.
(c) Metabolic syndrome: Characterized by insulin resistance, glucose intolerance, hy-
pertension, central obesity, dyslipidaemias, endothelial dysfunction, increased oxida-
tive stress and a systemic inflammatory state, which predisposes to thrombosis.
(d) Lipoprotein (a) levels: Lipoprotein (a) is an aberrant form of LDL that has the
apolipoprotein B-100 portion of LDL linked to apolipoprotein A. Increased levels
predispose to cardiovascular events.
(e) Factors affecting haemostasis: Several factors associated with coagulation and fibri-
nolysis are important predictors of cardiovascular events, eg, increased levels of
plasminogen activator inhibitor is associated with myocardial infarction and stroke.
(f) Physical inactivity and lack of exercise: A sedentary lifestyle predisposes to
atherosclerosis.

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