Ramazani, Noyan

Abstract Obesity has emerged as one of the most significant health challenges, with prevalence rates exceeding 30% in many regions and contributing substantially to the burden of cardiovascular disease (CVD). This review synthesized findings from clinical trials, systematic reviews, and narrative reviews. Key outcomes assessed included heart failure symptoms, echocardiographic parameters, incidence of atrial fibrillation (AF), inflammation biomarkers, and overall cardiovascular morbidity and mortality. Across studies, obesity was consistently linked with elevated risk of coronary heart disease, AF, stroke, and heart failure with preserved ejection fraction (HFpEF). Central adiposity and ectopic fat depots, especially epicardial fat, emerged as critical mediators of CVD progression. Semaglutide, tirzepatide, and other agents have demonstrated robust effects in reducing weight, improving functional capacity, and attenuating cardiac remodeling, with additional benefits in lowering inflammation markers and natriuretic peptides independent of weight loss. Notably, patients with AF and obesity-related HFpEF appeared to experience greater symptomatic and functional improvements with semaglutide compared with those without AF. Conversely, evidence on the obesity paradox and metabolically healthy obesity revealed heterogeneity, with some subgroups demonstrating preserved or even improved survival despite excess adiposity, though these effects may be confounded by differences in cardiorespiratory fitness and lead time biases. Obesity remains a powerful risk factor for CVD, mediated through both metabolic and structural pathways. The advent of anti-obesity pharmacotherapies represents a watershed moment for cardiology, offering disease-modifying potential in obesity-related heart failure and beyond. Future research should refine the understanding of obesity phenotypes, and the role of fat distribution and cardiorespiratory fitness.