<B>ATHEROSCLEROSIS </B>

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ATHEROSCLEROSIS

Etiology:

• Unknown. Although the role of risk factors contributing to the pathogenesis is clear, the problem is that there are a few privileged individuals and experimental animals that are resistent when challenged by risk factors. Knowledge of the resistent factor(s) and their mechanism(s) of action would lead to a solution of the etiology.

Pathogenesis:

• Hypotheses: Endothelial damage (dysfuncton) with increased permeability, monocyte adhesion, and endothelial proliferation; hyperlipidemia with invasion of intima by foamy macrophages; macrphage derived cytokines (IL-1, TNF) and growth factors (PDGF, FGF) cause inflammatory response and proliferation of smooth muscle with sclerosis; plaque thickened by organization of superimposed thrombi.

Epidemiology:

• Causes 50% of all deaths in the U.S. due to coronary, cerebral, peripheral, and mesesteric vascular disease, and aortic aneurysms.
• A disease of western civilization. Absent in certain third world ethnic groups.
• Major risk factors are high animal fat diets, hyperlipdemias, hypertension, cigarette smoking, and diabetes.
• Other important risk factors are obesity, male gender, family history, and physical inactivity.

General Gross Description:

• Lesions in childhood appear as "fatty streaks".
• Adult plaques are discrete, yellow white random elevations, more prominent around ostia of large branches, abdominal aorta, and coronary popliteal, internal carotid, and cerebral arteries.
• Plaques may have sclerotic firm surfaces, or ulcerate with soft exposed grumous material.
• Plaques may become confluent with thrombosis.
• Severity increases with age, into very old age.

General Microscopic Description:

• An intimal lesion, made up of a deposition of neutral fats, cholesterol esters, necrotic debris and foam cells, with a variable chronic fibrotic inflammatory response forming a superficial fibrous cap containing smooth muscle and foam cells and lymphocytes.
• Complications are ulcers with thrombi, bleeding into plaque, embolization of thrombi and/or atheromas, calcifications, and atrophy of media with formation of aneurysms.

Clinical Correlations:

• Important clinical syndromes due to occlusive disease are ischemic heart disease (angina pectoris, myocardial infarction, congestive heart failure), cerebral infarcts, peripheral vascular disease with gangrene of legs, ischemic bowel disease with infarction. Ruptured abdominal aortic aneurysm also a significant cause of death.
• Advanced age not an indicator of immunity to atherosclerosis. Highest death rates by age are in those over 85 years old, 50 % or higher.

References:
•1. Robbins Pathologic Basis of Disease. Cotran, RS, Kumar, V, Robbins, SL, and Schoen, FJ. 5th Edition 1994. pp. 473-484.