Manifestations of human atherosclerosis across vascular beds

Abstract

Objective: Atherosclerosis underlies the most common etiologies of mortality worldwide, resulting in nearly 10 million deaths annually. In atherosclerosis, inflammation, metabolic factors, and hemodynamics cause the accumulation of extracellular lipids and the formation of plaques in the tunica intima of specific arteries. Atherosclerotic plaques primarily form in the coronary and carotid arteries, the aorta, and the peripheral arteries of the lower extremities. Although a common conceptual model of atherogenesis across these arteries has evolved over decades, there is a limited understanding of the important differences in regional atherosclerotic disease.

Methods: This review summarizes clinical studies, meta-analyses, and case reports to compare and contrast the impact, risk, plaque features, and clinical management of carotid, coronary, and femoral atherosclerosis in humans.

Results: Common risk factors, such as smoking and diabetes, influence disease risk differently across vascular beds. In addition, biological variables demonstrate a region-specific relationship with disease as peripheral atherosclerosis is most heritable, and male sex increases the risk of coronary and carotid, but not peripheral artery disease. The pathology of atherosclerotic lesions also varies between vascular territories. Specifically, carotid plaques are primarily lipid rich, whereas coronary plaques more commonly include fibrotic components with lipid-rich features, and femoral plaques are predominantly fibrocalcific. Clinically, interventional outcomes are worst in the carotid arteries and response to medical therapies, particularly statins, is not consistent across diseased regions, even within individual patients.

Conclusions: Atherosclerosis manifests in site-specific ways with regional differences in susceptibility and treatment response. Despite advances in the scientific understanding and clinical management of atherosclerosis, little is known about the mechanisms determining vessel-specific disease patterns and risk. Further research is needed urgently to delineate factors controlling plaque initiation and progression specific to vascular beds.

Keywords: Atherosclerosis; Carotid stenosis; Coronary artery disease; Peripheral arterial disease; Plaque.

Figure.

Plaque features in carotid, coronary, and peripheral atherosclerosis. Characteristics of the vascular territory and atherosclerotic plaque morphology including approximate cell type composition of plaques.