Coronary artery disease (CAD) is the main cause of morbidity and death worldwide, and atherosclerosis represents the leading pathophysiological pathway responsible for CAD. Atherosclerotic process is a complex interplay of mechanisms and mediators resulting in plaque formation, progression and destabilization, the latter being the most frequent cause of acute cardiovascular events. Considering the systemic nature of atherosclerosis, polyvascular disease involvement is possible and has been described since 1960s. Accordingly, epidemiologic studies reported that concomitant CAD and atherosclerosis in other arterial beds like carotid arteries, lower limb arteries, mesenteric and renal circulation, and aorta, is frequent and related to increased chance of future cardiovascular events. Although risk factors, atherosclerotic plaque features and mechanisms of plaque destabilization are largely shared across different sites, many studies have reported some disparities among districts. Moreover, simultaneous polyvascular disease has been associated with increased likelihood of having particular plaque characteristics depending on the affected arterial level. In this comprehensive narrative review, we aim to discuss about epidemiology of concomitant CAD and atherosclerosis in other arterial beds, and to examine differences in risk factors, plaque features and mechanisms of plaque instability between CAD and other atherosclerotic locations. Finally, we review the studies observing differences on plaque features according to involved atherosclerotic sites, focusing on CAD.

Intracoronary optical coherence tomography (OCT) is a highly accurate and sensitive imaging tool capable of providing high resolution visualization of atherosclerotic coronary plaque morphology and microstructures in vivo. OCT has proven to be useful in clinical practice, particularly in percutaneous coronary intervention (PCI) guidance, assessment of stent-related complications, and elucidation of the pathobiological cause of acute coronary syndrome. Notably, OCT allows for the detection of specific plaque features (i.e., thin cap fibroatheroma, lipid-rich plaque, macrophage infiltration, healed plaques, microvessels, etc.) that are known to carry prognostic significance in the context of coronary artery disease (CAD). These insights may offer valuable information about the patient’s overall atherosclerotic background, potentially supporting more personalized secondary prevention strategies, including lifestyle modification and targeted pharmacologic therapies. Recently, the role of preventive PCI in plaques with high-risk features has also been investigated with promising—though still preliminary—results. In this narrative review, we primarily aim to discuss studies evaluating the prognostic value of OCT-identified coronary plaque microstructures. We also assessed potential therapeutic implications in the management of patients with CAD.