Triglyceride-glucose body mass index and risk of incident venous thromboembolism: a prospective cohort study from the UK Biobank

BACKGROUND: Triglyceride-glucose body mass index (TyG-BMI) is an emerging surrogate indicator of insulin resistance adiposity, which has been demonstrated as a risk factor for various cardiovascular diseases including hypertension, and myocardial infarction. However, association of TyG-BMI with incident VTE remains to be investigated. METHODS: This study included 328,208 participants from the prospective UK Biobank cohort without baseline VTE. The primary outcome was incident VTE, and the second outcomes were incident pulmonary embolism (PE) and deep vein thrombosis (DVT). Multivariable-adjusted Cox proportional hazards regression and restricted cubic spline (RCS) analyses assessed the association between baseline TyG-BMI and incident VTE. Stratified analyses evaluated potential effect modification by age, sex, smoking, alcohol use, diabetes, hypertension, cancer, BMI, physical activity, and dietary quality. In addition, we estimated population attributable fractions (PAFs) for elevated TyG-BMI (quartiles above quartile 1). RESULTS: Over a median follow-up of 13.64 years, 8353 VTE events occurred. VTE incidence rose from 114.0 to 279.1 per 100,000 person-years across TyG-BMI quartiles. After full multivariable adjustment, the highest had elevated risks of VTE (HR 2.10, 95% CI 1.94-2.26), PE (HR 2.28, 95% CI 2.06-2.52), and DVT (HR 1.88, 95% CI 1.66-2.12) compared with the lowest quartile. Risk rose sharply and non-linearly beyond a TyG-BMI threshold of 231.9. Associations were stronger among women, younger participants (< 60 years), non-smokers, and individuals not on lipid-lowering therapy, and remained robust in sensitivity analyses. The PAF for VTE was 0.333 (95% CI 0.295-0.371), for PE 0.376 (0.328-0.419), and for DVT 0.276 (0.212-0.341). CONCLUSIONS: Higher TyG-BMI independently predicts increased risk of first-ever VTE, underscoring its utility as a composite biomarker for identifying individuals at heightened thrombotic risk related to metabolic dysfunction and obesity.