Evolving concepts of the vulnerable atherosclerotic plaque and the vulnerable patient: implications for patient care and future research

Understanding the natural history of coronary artery atherosclerosis is necessary to determine prognosis and prescribe effective therapies. Traditional management of coronary artery disease has focused on the treatment of flow-limiting anatomical obstructions that lead to ischaemia. In most scenarios, revascularization of these atherosclerotic plaques has not substantially improved freedom from death or myocardial infarction, questioning the utility of contemporary revascularization strategies to improve prognosis. Advances in non-invasive and invasive imaging techniques have helped to identify the characteristics of obstructive and non-obstructive plaques that are precursors for plaque progression and future acute coronary syndromes as well as cardiac death. These ‘vulnerable plaques’ develop as a consequence of systemic inflammation and are prone to inducing thrombosis. Vulnerable plaques most commonly have a large plaque burden with a well-formed necrotic core and thin fibrous cap and are metabolically active. Perivascular adipose tissue might, in some patients, be used as a surrogate for coronary inflammation and predict future risk of adverse cardiac events. Vulnerable plaques can be identified in their quiescent state, offering the potential for therapeutic passivation. In this Review, we describe the biological and compositional features of vulnerable plaques, the non-invasive and invasive diagnostic modalities to characterize vulnerable plaques, the prognostic utility of identifying vulnerable plaques, and the future studies needed to explore the value of intensified pharmacological and focal treatments of vulnerable plaques. In this Review, the authors describe the features of coronary artery vulnerable plaques as well as non-invasive and invasive diagnostic modalities that can be used to characterize them. They also discuss the prognostic utility of identifying vulnerable plaques and the best current approaches to manage these lesions, and highlight evidence gaps and future directions. Key points Vulnerable plaques are atherosclerotic coronary lesions prone to thrombosis owing to their specific structure and biological and chemical features. Non-invasive and invasive diagnostic modalities, including CT angiography and catheter-based imaging techniques, have been developed to detect these lesions before they cause adverse cardiovascular events. Pharmacological and interventional treatments of vulnerable plaques have been shown to favourably alter