Leukocyte Regulation by Exercise and Complementary Lifestyle Factors in Cardiovascular Health

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, underscoring the need for effective preventive and therapeutic strategies. Chronic inflammation and immune dysregulation contribute to CVD development, with leukocytes linking systemic immune responses to vascular and myocardial injury. Regular exercise is a cornerstone of non-pharmacological cardiovascular prevention and exerts immunomodulatory effects beyond conventional risk-factor control by regulating leukocyte production, trafficking, immunometabolism, and effector functions. Diet, sleep, circadian rhythms, and psychological stress also influence leukocyte-mediated immune regulation through interconnected metabolic, neuroendocrine, and microbiota-related pathways. This review integrates mechanistic evidence on how these lifestyle factors shape leukocyte-mediated immunity in cardiovascular health and disease. Acute exercise induces transient catecholamine-mediated leukocyte mobilization and redistribution, with responses generally increasing with exercise intensity and duration, whereas regular training may produce more sustained changes in hematopoiesis, immunometabolism, and inflammatory function. These adaptations are influenced by cumulative training load and recovery, with experimental studies implicating adipose-derived leptin signaling and myeloid metabolic reprogramming as potential mechanisms. Importantly, transient changes in circulating leukocyte counts do not necessarily indicate sustained functional adaptations, and whether leukocyte regulation directly mediates cardiovascular benefits remains uncertain, particularly in humans. We further identify key mechanistic and translational gaps that must be addressed to develop more targeted lifestyle strategies for CVD prevention and management.