Association of Non-Insulin-Based Insulin Resistance Indices With Risk of Incident Valvular Heart Disease: Results From the UK Biobank Cohort Study.

BACKGROUND: Non-insulin-based insulin resistance (IR) indices, including the estimated glucose disposal rate (eGDR), metabolic score for IR, and triglyceride-glucose indices (TyG-BMI, TyG-WC), have been implicated in cardiovascular diseases. However, few studies have investigated their associations with valvular heart disease (VHD). METHODS: We conducted a prospective cohort study of 354 265 eligible participants from the UK Biobank. The primary outcome was incident VHD, including aortic valve stenosis, mitral valve regurgitation, and aortic valve regurgitation. eGDR, metabolic score for IR, TyG-BMI, and TyG-WC were categorized into quartiles, with eGDR ranked inversely due to its negative correlation with IR. Multivariable Cox proportional hazards regression was used to assess associations between IR indices and VHD risk. RESULTS: Over a median follow-up of 13.60 years, 8568 (2.42%) participants developed VHD, including 3793 (1.07%) aortic valve stenosis, 1371 (0.39%) aortic valve regurgitation, and 4040 (1.14%) mitral valve regurgitation cases. Participants in the highest quartile of non-insulin-based IR indices had significantly higher risks of incident VHD, with hazard ratios of 1.90 (95% CI, 1.75-2.06) for eGDR, 1.53 (95% CI, 1.41-1.65) for TyG-WC, 1.52 (95% CI, 1.42-1.63) for TyG-BMI, and 1.25 (95% CI, 1.17-1.34) for metabolic score for IR. The strongest associations were observed with aortic valve stenosis, with hazard ratios of 2.95 and 2.43 for eGDR and TyG-WC, respectively. Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: Non-insulin-based IR indices, including eGDR, metabolic score for IR, TyG-BMI, and TyG-WC, are significantly associated with increased risk of incident VHD, particularly aortic valve stenosis. These findings may contribute to improved early risk stratification and targeted prevention strategies for VHD.