Associations Between Metabolic Score for Visceral Fat and Venous Thromboembolism Among 118 619 Participants With Metabolic Syndrome: Insights From Epidemiology to Genetic Susceptibility

BACKGROUND: Metabolic syndrome substantially elevates venous thromboembolism (VTE) risk, increasing health care burdens. The Metabolic Score for Visceral Fat (METS-VF) offers a novel, simplified approach to assess visceral fat. This study evaluates METS-VF's association with VTE risk and its utility for risk stratification in patients with metabolic syndrome. METHODS: Using UK Biobank data, we included 118 619 participants with metabolic syndrome free of VTE at baseline. Time-dependent area under the curve analysis with bootstrap validation identified the strongest VTE predictor. Multivariable Cox models assessed associations of METS-VF, a VTE-specific polygenic risk score, and their combination with incident VTE. Mediation analysis evaluated potential mediators. Robustness was assessed through subgroup and sensitivity analyses, including competing risk of death. RESULTS: Over a median 12-year follow-up, 5162 participants developed VTE. METS-VF demonstrated stronger association with VTE than traditional metabolic indicators. Highest quartile participants showed significantly increased risks of VTE (hazard ratio [HR], 1.46 [95% CI, 1.33-1.61]), pulmonary embolism (HR, 1.50 [95% CI, 1.33-1.70]), deep vein thrombosis (HR, 1.52 [95% CI, 1.34-1.73]), and lower-extremity deep vein thrombosis (HR, 1.59 [95% CI, 1.38-1.82]). Stratified analysis revealed synergistic interaction between METS-VF and genetic susceptibility. CRP (C-reactive protein) and estimated glomerular filtration rate significantly mediated the METS-VF-VTE association. CONCLUSIONS: METS-VF is a significant, independent risk indicator for VTE in patients with metabolic syndrome, demonstrating synergistic effects with genetic risk. The CRP- and estimated glomerular filtration rate-mediated association supports METS-VF's clinical utility in VTE risk stratification.