The changing landscape of atherosclerosis

Abstract

Emerging evidence has spurred considerable evolution of concepts of atherosclerosis and called into question many cherished notions. Atherosclerosis risk no longer concentrates in Western countries, but now reaches globally to cause the majority of deaths worldwide. Atherosclerosis currently affects younger people, more women, and non-Caucasians than formerly. The risk factor profile has shifted as low-density lipoprotein (LDL) cholesterol, blood pressure, and smoking have decreased. Recent research has challenged the protective effects of high-density lipoprotein (HDL), as focus has shifted toward triglyceride-rich lipoproteins as causal in atherosclerosis. Beyond lipids, nontraditional drivers of atherosclerosis such as disturbed sleep, the microbiome, air pollution, and environmental stress have gained attention. Inflammatory pathways and leukocytes link traditional and emerging risk factors alike to altered behavior of arterial wall cells. Probing the pathogenesis of atherosclerosis has reached into the bone marrow. Somatic mutations in stem cells can cause clonal hematopoiesis, a previously unrecognized but common and potent age-related contributor to cardiovascular risk. The mechanisms of the thrombotic complications of atherosclerosis have evolved beyond the “vulnerable plaque” concept. These advances in the understanding of the biology of atherosclerosis have opened new avenues to therapeutic interventions that promise to advance the prevention and treatment of this now ubiquitous disease.