Frailty index predicts hearing loss in middle-aged and older adults: A triangulated analysis of global, cohort, and genetic data

OBJECTIVE: To examine the association between frailty (Frailty Index, FI) and incident hearing loss using triangulation across GBD 2021, CHARLS, and Mendelian Randomization (MR). METHODS: Global trends were analyzed with GBD 2021. In CHARLS (2011-2020), FI was calculated for adults ≥ 45-years. Associations with incident hearing loss were assessed using logistic regression, restricted cubic splines, and ROC curves. Two-sample MR employed inverse-variance weighted, weighted median, and MR-Egger methods. RESULTS: GBD revealed increasing hearing loss burden globally, especially among older adults in low- and middle-income countries. In CHARLS, higher FI independently predicted incident hearing loss: moderate frailty increased odds by 66% (OR = 1.66, 95% CI: 1.29-2.12) and severe frailty by 141% (OR = 2.41, 95% CI: 1.47-3.95). Each unit FI increase conferred a 9% higher risk (OR = 1.09, 95% CI: 1.04-1.14). RCS identified a nonlinear threshold (FI ≈ 0.29). Adding FI to conventional risk factors improved prediction (AUC: 0.586 to 0.685). MR supported a causal effect of genetically predicted frailty on hearing loss with no evidence of pleiotropy. CONCLUSION: The Frailty Index is a robust, independent, and nonlinear predictor of incident hearing loss. Integrating frailty assessment enhances early identification and supports targeted prevention. LEVEL OF EVIDENCE: II.