No abstract

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Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstructblood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable angina pectoris and the acute coronary syndromes. Atherosclerosis is a lipoprotein-driven disease that leads to plaque formation at specific sites of the arterial tree through intimal inflammation, necrosis, fibrosis, and calcification. After decades of indolent progression, such plaques may suddenly cause life-threatening coronary thrombosis presenting as an acute coronary syndrome. Most often, the culprit morphology is plaque rupture with exposure of highly thrombogenic, red cell-rich necrotic core material. The permissive structural requirement for this to occur is an extremely thin fibrous cap, and thus, ruptures occur mainly among lesions defined as thin-cap fibroatheromas. Also common are thrombi forming on lesions without rupture (plaque erosion), most often on pathological intimal thickening or fibroatheromas. However, the mechanisms involved in plaque erosion remain largely unknown, although coronary spasm is suspected. The calcified nodule has been suggested as a rare cause of coronary thrombosis in highly calcified and tortious arteries in older individuals. To characterize the severity and prognosis of plaques, several terms are used. Plaque burden denotes the extent of disease, whereas plaque activity is an ambiguous term, which may refer to one of several processes that characterize progression. Plaque vulnerability describes the short-term risk of precipitating symptomatic thrombosis. In this review, we discuss mechanisms of atherosclerotic plaque initiation and progression; how plaques suddenly precipitate life-threatening thrombi; and the concepts of plaque burden, activity, and vulnerability. (Circ Res.

Atherosclerosis is a multifocal, smoldering, immunoinflammatory disease of medium-sized and large arteries fuelled by lipids. Endothelial cells, leukocytes, and intimal smooth muscle cells are the major players in the development of this disease. The most devastating consequences of atherosclerosis, such as heart attack and stroke, are caused by superimposed thrombosis. Therefore, the vital question is not why atherosclerosis develops but rather why atherosclerosis, after years of indolent growth, suddenly becomes complicated with luminal thrombosis. If thrombosis-prone plaques could be detected and thrombosis averted, atherosclerosis would be a much more benign disease. Approximately 76% of all fatal coronary thrombi are precipitated by plaque rupture. Plaque rupture is a more frequent cause of coronary thrombosis in men (approximately 80%) than in women (approximately 60%). Ruptured plaques are characterized by a large lipid-rich core, a thin fibrous cap that contains few smooth muscle cells and many macrophages, angiogenesis, adventitial inflammation, and outward remodeling. Plaque rupture is the most common cause of coronary thrombosis. Ruptured plaques and, by inference, rupture-prone plaques have characteristic pathoanatomical features that might be useful for their detection in vivo by imaging. This article describes the pathogenesis of atherosclerosis, how it begets thrombosis, and the possibility to detect thrombosis-prone plaques and prevent heart attack.