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.