Pathophysiology of plaque disruption and thrombosis in acute ischemic syndromes

Atherosclerosis is a systemic disease responsible for strokes, myocardial infarction, renal hypertension, and intermittent claudication. Acute coronary syndromes (unstable angina, acute myocardial infarction, and sudden cardiac death) are the major causes of morbidity and mortality in developed countries. These acute manifestations of heart disease share a common pathophysiologic phenomenon: coronary thrombosis. Two principal mechanisms are responsible for coronary thrombosis: plaque disruption (75%) and plaque erosion (25%). Disrupted plaques exhibit a large lipid content, increased macrophages, and a thin fibrous cap. Hypercholesterolemia and diabetes are associated with plaque disruption. Eroded plaques are smooth muscle-cell rich with an intact fibrous cap. Cigarette smoking is associated with plaque erosion, most frequently in women with sudden death when they are younger than 50 years of age. Systemic inflammation is a novel, robust marker for future cardiovascular events, not only in patients with established atherosclerotic disease but also in apparently healthy individuals. Local inflammation at the plaque disruption site is documented by increased macrophage infiltration. Macrophages are responsible for plaque disruption, neovascularization, smooth muscle cell apoptosis, and plaque thrombogenicity. Experimental studies have identified the lipid core as the most thrombogenic substrate of the atherosclerotic plaque. Tissue factor, a cell membrane-bound protein, is crucial in thrombus formation. Tissue factor is expressed in apoptotic macrophages, suggesting that macrophages are not only responsible for plaque disruption but also pivotal in thrombus generation, the most important mechanism of acute coronary syndromes.