Metabolic Flexibility as a Bridge Between Endocrine Dysfunction and Cardiovascular Disease: Implications for Modern Risk Assessment

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Abstract
Cardiovascular disease remains the leading cause of mortality worldwide, and traditional risk stratification models based on static variables are often insufficient to explain the complexity of cardiometabolic disorders. In this context, metabolic flexibility—defined as the ability of the organism to adapt substrate utilization according to physiological demands—has emerged as a relevant integrative concept linking endocrinology and cardiovascular disease. This review analyzes metabolic flexibility as a central mechanism in cardiovascular risk, exploring its physiological basis, its relationship with insulin resistance and metabolic disorders, and its implications in cardiovascular pathology. Evidence shows that impaired metabolic flexibility is associated with altered substrate utilization, mitochondrial dysfunction, systemic inflammation, and increased cardiovascular risk. These alterations contribute to inefficient myocardial energy metabolism, vascular dysfunction, and disease progression. Additionally, current therapeutic strategies that improve metabolic regulation have demonstrated significant cardiovascular benefits, supporting the relevance of metabolic pathways in disease prevention and management. The analysis also highlights the importance of considering metabolic flexibility in populations with a high burden of cardiometabolic disease, particularly in Latin American countries such as Mexico, Colombia, and Ecuador.