Exercise in Patients with Subclinical Atherosclerosis: Mechanisms, Clinical Evidence, and Practical Recommendations

Subclinical atherosclerosis represents an important stage in the continuum of cardiovascular disease, characterized by structural or functional vascular abnormalities in the absence of overt clinical events. This review examines the biological mechanisms and clinical evidence supporting exercise as both a preventive and potential disease-modifying intervention in individuals with imaging-detected subclinical atherosclerosis, with particular emphasis on endothelial function, vascular remodeling, inflammation, plaque composition, and cardiovascular risk.

Increasing evidence indicates that exercise exerts vascular effects that extend beyond conventional risk-factor modification. Exercise improves endothelial function, vascular compliance, and nitric oxide bioavailability through shear stress-mediated activation of endothelial nitric oxide synthase (eNOS), while also modulating oxidative stress, myokine signaling, vascular inflammation, and macrophage phenotype. These effects may promote plaque stabilization and influence atherosclerotic lesion composition. Importantly, exercise-associated increases in coronary artery calcium observed in highly active individuals may reflect a shift toward more densely calcified and potentially more stable plaque rather than an accumulation of high-risk lipid-rich lesions. Clinical and meta-analytic evidence further suggests modality-specific effects, with interval training showing favorable effects on arterial stiffness and combined aerobic-resistance training improving endothelial function. Exercise may therefore complement pharmacological risk-factor modification by targeting vascular pathways that are not fully addressed by conventional therapies. Exercise should be considered an integral component of cardiovascular risk management in individuals with subclinical atherosclerosis rather than solely a primary-prevention strategy. Its potential benefits extend from improving vascular function and reducing inflammation to modifying plaque characteristics and promoting plaque stability. Future studies should determine whether exercise prescriptions can be individualized according to atherosclerotic burden, plaque phenotype, imaging characteristics, and circulating biomarkers to establish the optimal exercise modality, intensity, and dose across different patient populations.