Narrative review summarizes evidence on exercise benefits for cardiovascular disease and mortality risk reduction.

Cardiovascular disease (CVD) continues to be the leading cause of morbidity and mortality globally, imposing a substantial burden on healthcare systems worldwide. Physical inactivity is a significant modifiable risk factor that contributes to the onset and progression of CVD. Current guidelines recommend regular aerobic and muscle-strengthening exercise, with even below-guideline volumes reducing mortality risk significantly. Notably, even physical activity levels below these recommendations can significantly reduce mortality risk, emphasizing the importance of any movement over a sedentary lifestyle. Exercise functions as both a preventive and therapeutic intervention, helping individuals with and without CVD, including those recovering from myocardial infarction or managing heart failure. At the molecular level, the IGF-1/PI3K/Akt signaling pathway plays a crucial role in exercise-induced cardiac protection by promoting balanced cardiac growth, enhancing contractility, and reducing fibrosis. Furthermore, increased endothelial nitric oxide synthase (eNOS) activity improves vascular function, antioxidant enzymes mitigate oxidative stress, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) stimulates mitochondrial biogenesis, while pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are downregulated. Large-scale cohort studies have proved that regular exercise can reduce all-cause and CVD mortality by 36%–56%. This magnitude of risk reduction rivals or exceeds that achieved by pharmacological interventions such as statins or antihypertensives, positioning physical activity as a foundational, cost-effective intervention for population-level cardiovascular disease prevention. However, excessive exercise may pose risks such as arrhythmias or myocardial strain, underscoring the need for personalized, balanced exercise programs. Future research should focus on defining best exercise prescriptions, understanding exercise–drug interactions, and developing biomarkers to check adaptive responses. Ultimately, integrating personalized exercise medicine into healthcare and public policy offers a cost-effective strategy for preventing and managing CVD, promoting lifelong cardiovascular resilience and well-being.