Combined Physical Activity in the Prevention of Cardiovascular Diseases: From Physiological to Molecular Mechanisms of Adaptation

Physical activity is recognized as a key non-pharmacological strategy for the prevention of cardiovascular diseases (CVD). However, the highest preventive efficacy is demonstrated by exercise programs that combine different types of physical loads. This review summarizes current scientific evidence on the effects of combined physical activity, which integrates moderate- and high-intensity aerobic exercise with resistance training, on cardiometabolic regulation. The paper outlines multilevel mechanisms of adaptation, encompassing physiological, autonomic, hormonal, molecular, and epigenetic processes. It is shown that such combined exercise regimens produce a synergistic effect, contributing to blood pressure reduction, enhancement of heart rate variability, improvement of insulin sensitivity, suppression of chronic inflammation, and activation of cardioprotective transcriptional programs. Particular attention is paid to key molecular pathways involved in adaptive responses (AMPK, mTOR, PGC-1α, autophagy, unfolded protein response), as well as to the role of exerkines — signaling molecules secreted in response to muscular activity. Epigenetic modifications, including DNA methylation, microRNA regulation, and telomere maintenance, are also discussed as long-term mechanisms of cardiovascular protection. The presented findings emphasize the importance of implementing combined physical activity protocols in both personalized and population-based prevention strategies. Furthermore, additional studies are required to define the optimal balance of intensity, volume, and exercise modality across different population groups in order to maximize cardiovascular benefits and adaptive potential.