Determinants of thrombosis after plaque rupture

Atherosclerotic disease is the most frequent underlying cause of ischemic heart and cerebrovascular disease, and its thrombotic complications are the major cause of mortality and morbidity in the United States and Western countries. The most up-to-date statistical data suggest that cardiovascular diseases are responsible for one of four deaths in the United States. However, atherosclerotic disease, defined as thickening of the arterial wall caused by the accumulation of intracellular and extracellular lipids, macrophages, T cells, smooth muscle cells, proteoglycans, collagen, calcium, and necrotic debris, is rarely fatal. The mechanisms responsible for the conversion of a stable and clinically silent atherosclerotic lesion to a life-threatening condition is plaque disruption. The important socioeconomic implications of atherosclerotic disease arise from the impact of the acute plaque disruption syndromes (unstable angina, acute myocardial infarction, stroke, and even sudden death). Clinical, experimental, and postmortem evidence has clearly demonstrated the critical role of acute thrombosis after plaque disruption, not only in the pathogenesis of atherosclerotic disease but also in the onset of acute coronary syndromes. Because of these observations, the more relevant therapeutic approaches to reduce the impact of atherosclerosis on our society are those directed against the conditions involved in the instability or disruption of plaques and, those specifically directed toward reducing the thrombotic consequences of plaque disruption.