Long-term oral anticoagulant treatment after myocardial infarction : results of the 'Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis' (ASPECT) trial

Despite the fact that mortality from cardiovascular diseases has declined considerably over the last decades, it still represents the leading cause of mortality and morbidity in industrialized countries. Most clinical manifestations of cardiovascular disease share the underlying pathophysiological process of atherosclerosis. Atherosclerosis is a diseased state of the intima and media of medium to large sized arteries characterized by focal plaques preferentially located in areas of low shear. It is assumed that plaques origin from fatty streaks that are initiated by oxidation of low density lipoprotein. Formation of fatty streaks may also follow initial injury from a wide range of agents including toxins, viral infections and intraluminal devices such as catheters. The subsequent inflammatory reactions induce smooth muscle proliferation by growth factor production from a wide range of cells including platelets, endothelial cells, macrophages, and other smooth muscle cells. The development of fatty streaks may already commence early in childhood and progress over a period of decades to become atherosclerotic plaques which contain lipid-filled foam cells, extracellular lipid and a layer of smooth muscle cells just beneath the endothelium.' Plaque growth is mediated by the proliferation of smooth muscle cells and extracellular connective tissue elements such as collagen, elastin, and proteoglycans. Growth factors derived from the interaction between platelets and the underlying artery wall further stimulates this process. This process will lead to the formation of a fibrolipid plaque that constitutes a core of extracellular lipid separated from the media by smooth muscle cells and covered and separated from the lumen by a thick cap of collagen-rich fibrous tissue containing smooth muscle cells. Surrounding the lipid core are lipid-filled foam cells. Elevated coronary plaques may cause clinical symptoms when the plaque size is sufficient to obstruct the normal bloodflow, usually when it occupies more than 40 percent of the original cross-sectional area of the lumen. As the result of a dynamic interplay between plaque vulnerability, possibly mediated through a process of inflammation, and external stresses the atherosclerotic plaque surface may eventually rupture.

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