Comparison of the triglyceride-glucose index and its modified indices for predicting mortality in advanced CLKM syndrome.

BACKGROUND: The prognostic utility of the triglyceride-glucose (TyG) index and its anthropometry-enhanced variants (TyG-WC, TyG-WHtR, TyG-BMI) for mortality risk in advanced cardiovascular-liver-kidney-metabolic syndrome (CLKM), a multisystem condition involving heart, liver, kidney, and metabolic health, remains unknown. METHODS: This nationwide prospective cohort study included 1384 adults with advanced CLKM syndrome from NHANES 1999-2018. The associations between the TyG index, its modified variants, and all-cause mortality were assessed using weighted multivariable Cox proportional hazards models. Restricted cubic splines (RCS) were used to identify nonlinear associations. To compare predictive performance, C-index, net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated. RESULTS: Over a mean 56-month follow-up, 360 deaths were recorded. RCS revealed U-shaped associations (i.e., lower risk at intermediate levels and higher risk at both low and high levels) between TyG indices and mortality (P for nonlinear< 0.05), with inflection points at TyG = 9.56, TyG-WC = 1,039.11, TyG-WHtR = 5.17, and TyG-BMI = 215.85. At values below the inflection points, higher indices were associated with reduced mortality risk. Comparison based on the C-index, NRI, and IDI showed that the modified TyG indices did not outperform the original TyG in mortality prediction. Subgroup analyses confirmed consistency (P for interaction >0.05). CONCLUSION: In advanced CLKM syndrome, TyG indices exhibit U-shaped mortality association, revealing dual metabolic roles. The original TyG index performs comparably to anthropometry-enhanced variants, supporting its use as a parsimonious risk-stratification tool. Identified inflection points offer actionable thresholds for personalized management.