Requiem for the ‘vulnerable plaque’

Abstract

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. Challenges to the ‘vulnerable plaque’ concept Thin-capped, lipid-rich atheromata are not solitary, rather often multiple, and affect several arterial beds in the same individual. Thin-capped, lipid-rich atheromata most often persist for years without causing a clinical event. The risk profile and demographics of acute coronary syndrome patients are shifting worldwide (global burden, younger patients, more women, more insulin resistance/diabetes, more hypertriglyceridaemia, and less low-density lipoprotein excess). Statin treatment and other preventive measures have begun to modify atherosclerotic disease. ST segment elevation myocardial infarction wanes as non-ST segment elevation myocardial infarction waxes. Plaque rupture declines as a cause of acute coronary syndromes while superficial erosion appears on the rise. Plaques underlying cerebrovascular events reveal more ‘stable’ fibrous characteristics compared with that 10 years ago. Thin-capped, lipid-rich atheromata are not solitary, rather often multiple, and affect several arterial beds in the same individual. Thin-capped, lipid-rich atheromata most often persist for years without causing a clinical event. The risk profile and demographics of acute coronary syndrome patients are shifting worldwide (global burden, younger patients, more women, more insulin resistance/diabetes, more hypertriglyceridaemia, and less low-density lipoprotein excess). Statin treatment and other preventive measures have begun to modify atherosclerotic disease. ST segment elevation myocardial infarction wanes as non-ST segment elevation myocardial infarction waxes. Plaque rupture declines as a cause of acute coronary syndromes while superficial erosion appears on the rise. Plaques underlying cerebrovascular events reveal more ‘stable’ fibrous characteristics compared with that 10 years ago. Challenges to the ‘vulnerable plaque’ concept Thin-capped, lipid-rich atheromata are not solitary, rather often multiple, and affect several arterial beds in the same individual. Thin-capped, lipid-rich atheromata most often persist for years without causing a clinical event. The risk profile and demographics of acute coronary syndrome patients are shifting worldwide (global burden, younger patients, more women, more insulin resistance/diabetes, more hypertriglyceridaemia, and less low-density lipoprotein excess). Statin treatment and other preventive measures have begun to modify atherosclerotic disease. ST segment elevation myocardial infarction wanes as non-ST segment elevation myocardial infarction waxes. Plaque rupture declines as a cause of acute coronary syndromes while superficial erosion appears on the rise. Plaques underlying cerebrovascular events reveal more ‘stable’ fibrous characteristics compared with that 10 years ago. Thin-capped, lipid-rich atheromata are not solitary, rather often multiple, and affect several arterial beds in the same individual. Thin-capped, lipid-rich atheromata most often persist for years without causing a clinical event. The risk profile and demographics of acute coronary syndrome patients are shifting worldwide (global burden, younger patients, more women, more insulin resistance/diabetes, more hype