TYGFI and Stroke Risk in US Older Adults

BackgroundThe triglyceride-glucose-frailty index (TYGFI) is an emerging marker of metabolic-geriatric risk; however, its association with stroke and the mediating role of body mass index (BMI) remain underexplored in large, representative populations. MethodsWe conducted a cross-sectional analysis of 9,913 adults aged [&ge;]50 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Stroke was defined based on self-reported diagnosis. TYGFI was calculated as a composite of the triglyceride-glucose (TyG) index and the frailty index (FI). BMI was evaluated as a continuous mediator. We employed multivariable logistic regression, restricted cubic spline (RCS) models, threshold effect analysis, receiver operating characteristic (ROC) curve analysis, subgroup analysis, and causal mediation analysis, adjusting for key sociodemographic and clinical confounders. ResultsElevated TYGFI was strongly associated with increased odds of stroke (fully adjusted odds ratio OR = 3.64, 95% confidence interval CI: 3.06-4.33, p < 0.001). RCS analysis revealed a significant nonlinear positive relationship (p-nonlinearity < 0.001), with an inflection point identified at TYGFI = 1.094. TYGFI was positively associated with BMI (fully adjusted {beta} = 4.09, 95% CI: 3.78-4.41, p < 0.001). Causal mediation analysis indicated that BMI exerted a significant negative indirect effect on the TYGFI-stroke association in the core model (average causal mediation effect ACME =-0.0051, 95% CI:-0.0082 to-0.0025, p < 0.001), mediating -18.28% of the total effect. However, this indirect effect became negligible after adjusting for the body roundness index (BRI) (ACME = 0.0000, 95% CI:-0.0001 to 0.0003, p = 0.670). Subgroup analyses demonstrated consistent risk elevation across all strata (all p for interaction > 0.05). The fully adjusted model yielded an area under the curve (AUC) of 0.80 (95% CI: 0.78-0.82). ConclusionHigher TYGFI is robustly associated with increased stroke risk among US adults aged [&ge;]50 years. While BMI acts as a significant negative mediator, this effect is abrogated upon adjustment for central adiposity (BRI). These findings support a metabolic-geriatric pathway linking metabolic dysregulation, body composition, and cerebrovascular risk, positioning TYGFI as a promising target for stroke risk stratification in middle-aged and older adults.