Association between the triglyceride-glucose-frailty index and all-cause and cardiovascular mortality in individuals with cardiovascular-kidney-metabolic syndrome: the mediating role of the poverty-income ratio

cardiovascular-kidney-metabolic (CKM) syndrome involves complex interplay among metabolic, renal, and cardiovascular dysfunction. The triglyceride-glucose-frailty index (TyGFI) integrates insulin resistance (TyG) and functional decline (frailty), yet its association with mortality in CKM patients remains unexplored. Given that economic resources may influence mortality, whether the poverty–income ratio (PIR) mediates this association warrants investigation. This retrospective cohort study drew from the NHANES database for the period from 2005–2018 and included 15,044 participants diagnosed with CKM syndrome. The TyGFI was calculated as the mathematical product of the TyG index ln (triglycerides × fasting glucose/2) and the frailty index. Mortality outcomes were ascertained by linking records to the National Death Index and tracking participants until December 31, 2019. Kaplan‒Meier survival curves, Cox regression analysis, restricted cubic spline (RCS), mediation analysis, and subgroup analyses were applied to explore the association between the TyGFI and mortality. During a median observation period of 82 months (IQR: 46–123 months), 1,103 deaths from all causes and 353 cardiovascular deaths occurred. Kaplan‒Meier curves revealed substantially reduced death rates among participants in the lowest TyGFI tertile. Relative to the lowest TyGFI tertile, the highest tertile exhibited more than threefold increased risks for total mortality (HR = 3.14; 95% CI 2.57–3.83; P < 0.001) and cardiovascular mortality (HR = 3.14; 95% CI 2.18–4.52; P < 0.001) following comprehensive adjustment. When analysed continuously, every 1-unit increase in TyGFI corresponded to a 56% increase in the risk for all-cause mortality and a 52% increase in cardiovascular mortality risk. Mediation analysis revealed that PIR partially mediate the TyGFI-mortality association, accounting for 7.66% of all-cause mortality and 8.48% of cardiovascular mortality relationships. Subgroup analysis revealed consistent associations across demographic strata, with a significant interaction for marital status. TyGFI levels in individuals with CKM syndrome are nonlinearly associated with increased all-cause and cardiovascular mortality risk. Additionally, the PIR may partially mediate the TyGFI-mortality relationship, highlighting the possible role of socioeconomic factors. These findings support the use of the TyGFI as a valuable risk assessment tool for mortality evaluation in individuals with CKM syndrome.