The predictive value of estimated glucose disposal rate for the risk of venous thromboembolism in elderly individuals: a prospective cohort study of UK biobank

Background Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality, particularly among the elderly. Insulin resistance has been implicated in the pathogenesis of VTE. However, no prior study has investigated the associations between the estimated glucose disposal rate (eGDR), a surrogate marker for insulin resistance, and VTE risk in elderly individuals. Purpose This study aimed to investigate the predictive value of eGDR for the risk of VTE amongst elderly individuals. Methods We conducted a prospective cohort study using data from the UK Biobank, including 193,552 participants aged ≥60 years without a prior history of VTE. Participants were stratified into eGDR quartiles. The primary outcome was incident VTE, with secondary outcomes including pulmonary embolism (PE), deep vein thrombosis (DVT), and lower extremity DVT (LEDVT). Cox proportional hazards models, restricted cubic splines, and mediation analyses were employed to evaluate the relationship between eGDR and VTE risk. Polygenic risk scores were incorporated to account for genetic susceptibility. A LASSO regression model and an interpretable machine-learning framework (XGBoost) were employed to construct a predictive model for VTE risk. Results Over a median follow-up of 13.13 years, 8,670 VTE events were recorded. In fully adjusted models, the hazard ratio in the highest versus lowest eGDR quartiles was 0.71 [95% confidence interval (CI): 0.64-0.79] for VTE, 0.69 (95% CI: 0.60-0.79) for PE, 0.74 (95% CI: 0.64-0.84) for DVT, and 0.76 (95% CI: 0.66-0.88) for LEDVT, respectively. Restricted cubic splines revealed non-linear associations between eGDR and VTE, DVT, and LEDVT, with inflection points at eGDR values of 7.44 for VTE, 7.51 for DVT, and 7.55 for LEDVT. A linear inverse relationship was observed between eGDR and PE. Mediation analysis indicated that estimated glomerular filtration rate mediated 10.7% of the association between eGDR and VTE. Polygenic risk score analysis stratified by genetic risk demonstrated synergistic interaction between low eGDR and high genetic susceptibility. The risk prediction model identified eGDR as a key predictor of VTE. Conclusions Reduced eGDR is an independent predictor of VTE risk in elderly individuals, with distinct non-linear associations for VTE subtypes. Estimated glomerular filtration rate partially mediates the relationship between eGDR and VTE risk. The inclusion of eGDR in risk models enhances VTE risk stratification, particularly in individuals with a genetic predisposition.eGDR-genetic risk interaction Mean SHAP and feature importance plot