Abstract WE520: When Metabolism Breaks the Heart: Global Meta-analysis Linking Metabolic Syndrome to Heart Failure (≈5 Million Participants)

Background: Metabolic syndrome (MetS) accelerates cardiovascular remodeling through insulin resistance, adipose driven inflammation and neurohormonal activation, yet its contemporary association with heart failure (HF), particularly premature HF and sex based differences, remains underdefined. Methods: We conducted a PRISMA guided systematic review and meta analysis of observational studies (2015 to 2025) across PubMed, EMBASE, Scopus, Cochrane and Google Scholar. Adults 18 years and older with MetS (ATP III, IDF or WHO definition) were compared with non MetS populations for incident HF. Most adjusted hazard, risk or odds ratios were pooled using a random effects model. Prespecified subgroups included sex, age less than 50 versus 50 or older and HF phenotype (HFpEF and HFrEF). Heterogeneity was assessed using the I squared statistic with sensitivity analysis and Newcastle Ottawa quality scoring. Results: Thirty studies including 4.93 million participants were analyzed. MetS was associated with a 1.84 fold higher risk of incident HF (84 percent increase, 95 percent confidence interval 1.67 to 2.06, I squared 58 percent). The association was stronger in women (hazard ratio 1.98, 95 percent confidence interval 1.71 to 2.27) than men (hazard ratio 1.63, 95 percent confidence interval 1.44 to 1.86) and was greater in adults younger than 50 years (hazard ratio 2.21, 95 percent confidence interval 1.78 to 2.74), supporting premature cardiometabolic aging. Risk was elevated for HFpEF (hazard ratio 1.91, 95 percent confidence interval 1.60 to 2.28) and present for HFrEF (hazard ratio 1.54, 95 percent confidence interval 1.32 to 1.81). Findings were consistent in sensitivity analyses. Conclusions: In contemporary populations MetS confers a clinically meaningful increase in HF risk, disproportionately affecting women and younger adults. These findings support HFpEF as a metabolic disease and emphasize the need for early cardiometabolic screening and prevention, particularly for women under 50 years of age. Disclosures: No funding. No conflicts of interest.