Obesity and Metabolic Syndrome: Pathophysiological Mechanisms Driving Cardiovascular Risk

Abstract

Obesity and metabolic syndrome have become a significant public health issue, which has led to increasing rates of cardiovascular disease morbidity and mortality. This narrative review provides an overview of the most recent evidence (2017–2024) to update the underlying pathophysiological discussion on the relationships between adipose tissue dysfunction, chronic inflammation, insulin resistance, and ectopic lipid deposition, leading to the development of hemodynamic stress, endothelial dysfunction, and structural cardiac remodeling. Central pathophysiological derangements include adipokine dysfunction, lipotoxic injury from ceramides and diacylglycerols, and neurohormonal activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. These processes lead to a variety of cardiovascular phenotypes, such as heart failure with preserved ejection fraction (HFpEF), arrhythmias, atherosclerosis, and sudden cardiac death. From the clinical perspective, obesity increases diagnostic difficulties due to imaging artifacts of the epicardial fat and overlapping symptoms of HFpEF, so advanced biomarkers and individualized diagnostic methods are required. Novel approaches (lifestyle intervention, anti-diabetic drugs such as SGLT2 inhibitors, GLP-1 agonists, and bariatric surgery) have effectively reduced cardiovascular risk by acting on metabolic abnormalities, inflammation, and cardiac adaptation. The review signals the need for multifaceted care delivery models to integrate metabolic with cardiovascular risk management and the necessity for public health efforts to stem the tide of obesity and lead to equitable therapy access. Upcoming studies should focus on molecular mechanisms of cross-talk between the adipose and the organ system level and improve risk stratification tools to counteract the ongoing avalanche of obesity-associated cardiovascular disease.