Atherogenesis and thrombosis: Mechanisms, pathogenesis, and therapeutic implications

Abstract

Although the mortality rate from coronary heart disease (CHD) has declined by almost 50% during the past 25 years, CHD remains the leading cause of death in the United States and is responsible for more than 500,000 deaths annually. The underlying cause of CHD is coronary atherosclerosis. Although the intact intima is highly resistant to thrombus formation, when injury occurs, even superficial, a sequence of reactions is initiated—platelet aggregation, macrophage accumulation, intimal smooth muscle proliferation, fibrous tissue proliferation, and lipid accumulation—that result in the development of obstructive atheroma. Repeat intimal injury and cycling of this process lead to continued progression of the atheroma and coronary artery occlusion. Unstable angina and acute myocardial infarction appear to result from rupture of an atherosclerotic plaque, hemorrhage into the plaque, and luminal thrombosis. The cause of plaque rupture is unknown and may result from normal hemodynamic forces when the fibrous cap of an atheroma has become severely attenuated and fragile. Based on the pathogenesis of chronic atherosclerosis and acute rapid atheroma progression, several therapeutic options become evident. These include antiplatelet, anticoagulant, and thrombolytic therapies, as well as the possibility of arrest and reversal of atherosclerosis in some patients.