Requiem for the ‘vulnerable plaque’

The concept of the so-called ‘vulnerable plaque’ has proved highly useful to guide research and thinking regarding the pathophysiology of the acute coronary syndromes (ACS). Yet, the time may have come to reconsider this construct, as knowledge has accumulated, the risk profile of the populace has shifted, and our current therapies have reshaped the disease. Over the last several decades, the quest to identify and treat the ‘vulnerable plaque’ has generated much interest.1 Loaded with lipid, macrophage rich, covered by a thin fibrous cap, and considered perilously poised to rupture, the thin-capped fibroatheroma (TCFA) has become a target for imaging, possible intervention, model attempts in animals, and much discussion.2 Many equate type 1 myocardial infarction with ‘plaque rupture’. Yet, the ‘vulnerable plaque’ concept, as useful as it has proved heuristically, may not represent the contemporary challenge, an unmet clinical need, or a fertile field for future research. The notion of the ‘vulnerable plaque’ arose from autopsy studies that disclosed some two-thirds to three-fourths of fatal acute myocardial infarctions resulted from a fracture of the plaque's fibrous cap that engendered thrombosis ( Table 1 ; Figure 1 ). The elegant post-mortem studies of pathologist pioneers redirected the cardiology community from confusion about the causality of thrombosis in ACS and a focus on vasospasm towards plaque rupture.3,4 However compelling, the number of ruptured plaques resulting in luminal occlusion in these autopsy studies lacked a ‘denominator’. While such studies could interrogate the culprit of a fatal myocardial infarction, they did not determine how many plaques with morphologic characteristics associated with vulnerability did not cause a fatal rupture. View this table: Table 1 Challenges to the ‘vulnerable plaque’ concept Figure 1 Contrasts between …