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

Abstract

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.

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 the mechanical structure and composition of vulnerable plaques, which might lead to plaque stabilization and improve clinical outcomes.

  • Future large-scale, randomized, controlled clinical trials are needed to explore the value of intensified pharmacological and focal treatments of high-risk vulnerable plaques in vulnerable patients, that is, those patients who have an increased risk of cardiac events.

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Fig. 1: Major coronary atherosclerotic lesion types prone to thrombosis.
Fig. 2: Mechanisms of vulnerable atherosclerotic plaque formation and progression.
Fig. 3: Potential role of adipose tissue in cardiovascular inflammation and atherosclerosis.
Fig. 4: Features of high-risk vulnerable plaques on coronary CT angiography.
Fig. 5: Detection of high-risk vulnerable plaques on coronary MRI.
Fig. 6: Features of high-risk vulnerable plaques on coronary PET.
Fig. 7: Atherosclerotic plaque classification on intravascular ultrasonography.
Fig. 8: Vulnerable plaque features are associated with an increased risk of cardiac events.
Fig. 9: Algorithm for vulnerable plaque screening and treatment for primary prevention.

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P.G. and G.W.S. researched data for the article. All the authors contributed substantially to the discussion of content, wrote the manuscript, and reviewed and/or edited the manuscript before submission.

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Correspondence to Gregg W. Stone.

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J.M. cofounded Spectrawave. G.W.S. has received speaker honoraria from Infraredx, Medtronic and Pulnovo; has served as a consultant to Abiomed, Ablative Solutions, Amgen, Ancora, Apollo Therapeutics, Cardiomech, CorFlow, Elucid Bio, Gore, HeartFlow, Impulse Dynamics, Miracor, Neovasc, Occlutech, Robocath, Shockwave, TherOx, Valfix, Vascular Dynamics, Vectorious and V-Wave; and has equity/options from Ancora, Applied Therapeutics, Aria, Biostar family of funds, Cagent, Cardiac Success, Orchestra Biomed, Spectrawave, Valfix and Xenter. G.W.S.’s daughter is an employee at Medtronic. G.W.S.’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Biosense-Webster, Bioventrix, Cardiovascular Systems, Phillips, Shockwave, Vascular Dynamics and V-wave. The other authors declare no competing interests.

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Gaba, P., Gersh, B.J., Muller, J. et al. Evolving concepts of the vulnerable atherosclerotic plaque and the vulnerable patient: implications for patient care and future research. Nat Rev Cardiol (2022). https://doi.org/10.1038/s41569-022-00769-8

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