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