Plaque disruption and coronary thrombosis: new insight into pathogenesis and prevention

Clinical and pathologic studies have confirmed that disruption or superficial erosion of atherosclerotic plaque is the major cause of coronary thrombosis, which is the primary mechanism responsible for acute coronary syndromes of unstable angina, acute myocardial infarction, and sudden cardiac death. Serial angiographic studies have shown that nearly 60-70% of acute coronary syndromes evolve from mildly to moderately obstructive atherosclerotic plaques. The risk of plaque disruption appears to be a function of both plaque vulnerability (intrinsic factors) and extrinsic triggers, and is determined largely by the size of the lipid-rich atheromatous core, the thickness of the fibrous cap covering the core, and the presence of ongoing inflammation within and underneath the cap. Hemodynamic or mechanical stresses may precipitate plaque disruption, particularly in places where the fibrous cap is weakest, such as the shoulders. The degree of thrombosis following plaque disruption depends on the thrombogenicity of the disrupted plaque, the disturbed local rheology, and the systemic thrombotic-thrombolytic milieu. Surges in sympathetic activity (such as those provoked by sudden vigorous exercise, emotional stress, or cold weather) may also trigger plaque disruption. These observations have led to the concept of plaque stabilization as a new strategy for the prevention of acute coronary syndromes. Plaque stabilization can be achieved through pharmacologic and lifestyle-modifying interventions that alter plaque composition and/or inflammatory activity within the plaque and thus reduce its vulnerability to disruption.