Association of non-insulin-based insulin resistance indices with the risk of aortic stenosis progression in patients with mild or moderate aortic stenosis

BACKGROUND: Aortic stenosis (AS) is a common progressive valvular disease with no approved medical therapy to slow progression. Insulin resistance may contribute to valvular degeneration, but the prognostic value of non-insulin-based insulin resistance (IR) indices remains uncertain. METHODS: We retrospectively analyzed 2,220 patients with mild-to-moderate AS from the WenZhou Valve Heart Disease registry. Four IR surrogates were assessed: triglyceride-glucose (TyG) index, TyG-BMI, atherogenic index of plasma (AIP), and metabolic score for insulin resistance (METS-IR). AS progression was defined as an annual increase in peak aortic jet velocity (ΔVmax/year) ≥0.3 m/s/year. Associations and predictive performance were evaluated using multivariable Cox regression, Kaplan-Meier analysis, restricted cubic splines, ROC curves, and sensitivity analyses. RESULTS: During a median follow-up of 3.03 years, 414 patients (18.6%) developed AS progression. After multivariable adjustment, the highest tertiles of TyG, AIP, and TyG-BMI were independently associated with higher progression risk, with HRs of 1.58 (95% CI: 1.20-2.07), 1.43 (95% CI: 1.10-1.85), and 1.52 (95% CI: 1.18-1.95), respectively. TyG showed the strongest standalone discrimination (AUC 0.638), outperforming AIP and METS-IR. Associations were stronger in hypertensive patients. Adding IR indices modestly improved discrimination and reclassification, especially for TyG-BMI. Sensitivity analyses confirmed robustness. CONCLUSION: TyG and AIP were independently associated with non-severe AS progression, while TyG-BMI improved risk classification. These routine metabolic markers may help guide closer echocardiographic surveillance and metabolic risk management.