The Myth of the “Vulnerable Plaque”

Fro Me Ins Pe Lis Yo Ma The cardiovascular science community has pursued the quest to identify vulnerable atherosclerotic plaque in patients for decades, hoping to prevent acute coronary events. However, despite major advancements in imaging technology that allow visualization of rupture-prone plaques, clinical studies have not demonstrated improved risk prediction compared with traditional approaches. Considering the complex relationship between plaque rupture and acute coronary event risk suggested bypathology studies and confirmedby clinical investigations, these results are not surprising. This review summarizes the evidence supporting a multifaceted hypothesis of the natural history of atherosclerotic plaque rupture. Managing patients at risk of acute coronary eventsmandates a greater focus on the atherosclerotic disease burden rather thanon features of individual plaques. (J Am Coll Cardiol 2015;65:846–55) © 2015 by the American College of Cardiology Foundation. C ardiovascular atherosclerotic disease is the leading cause of death in Western industrialized nations and in developing countries (1). Strategies to prevent acute coronary events and their sequelae are among our most important public health priorities (2). Identifying patients at increased risk of acute coronary events who may benefit from intensified preventative measures is a major, ongoing challenge (2). Numerous factors (e.g., dyslipidemia, diabetes, and others), are associated with increased rates of adverse events; however, their hazard rates are too small for accurate individual risk assessments (3). The DIAD (Detection of Ischemia in Asymptomatic Diabetics) trial revealed that after 4.8 years of follow-up, 97% of asymptomatic patients with diabetes mellitus remained free of myocardial infarction and cardiac death (4). Even when combined as comprehensive risk scores (e.g., by the Framingham study [5]), predictive accuracy m the *Department of Medicine, Cardiology Division, Johns Hopkins Un dical Center, Icahn School of Medicine, New York, New York. Dr. Zadeh is titutes of Health. Dr. Fuster has reported that he has no relationships ter Libby, MD, served as Guest Editor for this paper. ten to this manuscript’s audio summary by JACC Editor-in-Chief Dr. Vale u can also listen to this issue’s audio summary by JACC Editor-in-Chief D nuscript received September 6, 2014; revised manuscript received Novem is insufficient for adequate individual risk assessments, leading to substantial overtreatment and undertreatment, with associated morbidity and societal costs (6). The mechanisms leading to adverse events from atherosclerotic disease are clearly more complex than initially assumed, explaining our difficulties in accurately predicting events in individuals (7,8). In addition to the presence, extent, and metabolic activity of atherosclerotic disease, individual adaptations and responses to thrombogenic stimulation from altered vascular function are critical for determining the risk of acute coronary events (7,9). Despite a consensus on the complexity of acute coronary event risk evaluation and the necessity for comprehensive patient assessment (10,11), recent efforts to identify high-risk patients have focused on using advanced imaging methods to detect single “vulnerable” atherosclerotic plaques (12). This narrow focus neglects the iversity, Baltimore, Maryland; and the yMount Sinai supported by grant K23-HL098368 from the National relevant to the contents of this paper to disclose. ntin Fuster. r. Valentin Fuster. ber 4, 2014, accepted November 25, 2014. FIGURE 1 Risk of MI or Death Associated With Individual Plaques in the PROSPECT Study