Heart Rate Variability in Cardiometabolic Disease: From Molecular Mechanisms to Personalized Exercise Prescription

Cardiometabolic diseases are characterized by interconnected disturbances in metabolic, inflammatory, mitochondrial, vascular, endocrine, and autonomic regulation, highlighting the need for integrative biomarkers capable of capturing systemic physiological dysfunction. Heart rate variability (HRV) provides a non-invasive and dynamic measure of cardiovascular autonomic regulation and may reflect the cumulative physiological consequences of these interacting alterations. This narrative review synthesizes current evidence on the role of HRV in cardiometabolic disease, with particular emphasis on the molecular and physiological mechanisms linking autonomic dysfunction with metabolic, inflammatory, mitochondrial, and vascular disturbances, as well as its potential application in individualized exercise prescription. Across obesity, metabolic syndrome, insulin resistance, type 2 diabetes, hypertension, and cardiovascular disease, reduced HRV is consistently associated with impaired autonomic adaptability and increased cardiometabolic risk. However, HRV should not be interpreted as a direct measure of sympathovagal balance or as a molecular biomarker; rather, it represents an integrative physiological signal influenced by multiple biological, behavioral, and environmental factors. Exercise may modulate autonomic regulation while simultaneously influencing metabolic signaling, inflammation, mitochondrial function, vascular health, and recovery, and accumulating evidence indicates that improvements in HRV may accompany favorable adaptations across diverse cardiometabolic populations. Accordingly, repeated HRV assessment may complement clinical, metabolic, functional, and body-composition measures to characterize physiological adaptation and support individualized adjustments in exercise prescription. Overall, HRV represents a promising integrative marker of cardiometabolic health and physiological resilience. Nevertheless, methodological heterogeneity, physiological confounding, and limited causal evidence currently constrain its clinical implementation. Standardized longitudinal and mechanistic studies are warranted to establish clinically meaningful HRV phenotypes, determine their capacity to predict individual exercise responsiveness, and clarify whether HRV-guided interventions can ultimately improve cardiometabolic outcomes.