Exercise, Atherosclerosis, and Cardiovascular Outcomes: Evidence and Challenges

Exercise is a cornerstone of cardiovascular primary prevention, yet its relationship with atherosclerosis is more complex than traditionally appreciated. Exercise improves the lipid profile by lowering total cholesterol, LDL-C, triglycerides, and apolipoprotein B, while increasing HDL-C and apolipoprotein A-I. It also enhances insulin sensitivity, lowers blood pressure, reduces body adiposity, and favorably influences glucose metabolism. In addition, it regulates oxidative stress and systemic inflammation, two key drivers of atherosclerosis. Exercise further exerts direct vascular effects by improving endothelial function, slowing plaque progression, and promoting a more stable plaque phenotype. Current evidence supports approximately 1000 MET-minute/week, roughly equivalent to 3 h/week of moderate-intensity exercise, as a pragmatic population-level target, with additional benefit from resistance training; however, the optimal prescription may vary among individuals. High-intensity interval training may further improve cardiorespiratory fitness and selected cardiometabolic parameters in appropriate individuals. Although highly trained endurance athletes may exhibit greater coronary artery plaque burden, available data suggest that their overall cardiovascular risk remains lower than sedentary individuals. In this review, we discuss the mechanisms through which exercise influences atherogenesis, review the evidence regarding different exercise types and patterns, and examine the clinical implications and future directions of exercise-based prevention strategies.