ABSTRACT
Coronary plaque rupture resulting in thrombotic occlusion is implicated in the pathogenesis of acute coronary syndromes (ACS).1-5 Focal flow-limiting coronary stenoses are the targets for revascularization to relieve myocardial ischemia.6 However, atherosclerosis is a widespread process,7-9 as most patients harbor diffuse disease. The recognition of the ubiquity of substantial but non-flow-limiting lesions, which may serve as the fodder for subsequent plaque rupture, has resulted in a paradigm shift in thinking about the pathophysiology of coronary artery disease, with the focus no longer solely on the degree of arterial luminal narrowing.1,6
Acute coronary syndromes result from rupture of macrophage-rich, inflamed thin-cap fibroatheroma (TCFA) with superimposed thrombus formation.1,8,9 The angiographic hallmark of ACS is a complex coronary culprit plaque characterized by fissuring, ulceration, haziness, and filling defect, which correlates with pathologic plaque rupture and thrombus.10-14 Plaque disruption is thought to be a function of the interplay between factors that influence intrinsic plaque vulnerability and extrinsic forces that may precipitate rupture.1,4,6,10,15-18 Until recently, plaque rupture was thought to reflect local plaque instability attributable to
spontaneous or triggered disruption of a lone vulnerable plaque, manifest angiographically or pathologically as a solitary complex unstable lesion. However, the pathophysiologic factors proposed to precipitate plaque instability, whether due to primary weakening of the fibrous cap attributable to inflammation6,15-18 or the extrinsic influences of intraluminal mechanical forces modulated by sympathetic tone and catecholamines,19,20 would be expected to exert their effects in a widespread pattern throughout the coronary vasculature. Recent observations now document that many patients with ACS harbor multiple complex unstable plaques by angiography.21 Multifocal plaque instability is evident not only in coronary vessels but also in peripheral vessels, and peripheral and coronary plaque instability may exist concomitantly.21,22 These observations support the concept that plaque instability is not merely a local vascular accident, but instead reflects more systemic pathophysiologic processes with the potential to destabilize atherosclerotic plaques throughout the cardiovascular system. This chapter will elucidate clinical and basic science data regarding:
• the prevalence of multifocal plaque instability in the coronary bed of patients with ACS
• evidence of pancoronary inflammation and its relationship to multifocal plaque instability
• links between systemic inflammation, multifocal plaque instability, plaque progression, and clinical outcomes
• evidence for panvascular plaque instability in coronary and extracoronary vascular beds.
