Evaluative performance of triglyceride-glucose-frailty index versus surrogate insulin resistance indices for advanced cardiovascular-kidney-metabolic syndrome, cardiometabolic multimorbidity, and mortality: the role of estimated glomerular filtration rate.

Higher TyG-FI quartiles were associated with markedly elevated odds of advanced cardiovascular-kidney-metabolic (CKM) syndrome compared to the lowest quartile.

• The highest TyG-FI quartile yielded OR = 4.57 (95% CI: 3.50–5.99) for advanced CKM syndrome compared with the lowest quartile.
• Analysis included 11,228 adults aged 20–79 years from NHANES 2001–2018.
• Survey-weighted logistic regression models were used with sequential adjustment for demographic, socioeconomic, and behavioral confounders.
• Dose-response patterns were non-linear (P for non-linearity < 0.001).

Higher TyG-FI quartiles were associated with markedly elevated odds of cardiometabolic multimorbidity (CMM).

• The highest TyG-FI quartile yielded OR = 5.09 (95% CI: 2.83–9.16) for CMM compared with the lowest quartile.
• Dose-response patterns were non-linear (P for non-linearity < 0.001).
• TyG-FI was calculated as the TyG index multiplied by the frailty index.
• Survey-weighted logistic models were used with sequential confounder adjustment.

Higher TyG-FI quartiles were associated with substantially elevated hazard for all-cause mortality.

• The highest TyG-FI quartile yielded HR = 3.90 (95% CI: 2.96–5.13) for all-cause death compared with the lowest quartile.
• Over a median follow-up of 90 months, there were 1,220 all-cause deaths.
• Among participants with CMM, the association with all-cause death remained (HR = 2.69, 95% CI: 1.69–4.28).
• Cox proportional-hazards models were used with sequential adjustment for confounders.
• Dose-response patterns were non-linear (P for non-linearity < 0.001).

Higher TyG-FI quartiles were associated with substantially elevated hazard for cardiovascular mortality.

• The highest TyG-FI quartile yielded HR = 5.82 (95% CI: 3.38–10.03) for cardiovascular death compared with the lowest quartile.
• Over a median follow-up of 90 months, there were 379 cardiovascular deaths.
• Dose-response patterns were non-linear (P for non-linearity < 0.001).
• Higher TyG-FI quartiles were associated with graded decreases in survival.

TyG-FI demonstrated higher discrimination for CKM syndrome, CMM, and mortality outcomes than most surrogate insulin resistance indices.

• Overall model performance was assessed using receiver operating characteristic curves with DeLong's test, time-dependent AUC, Harrell's C-index, calibration, and decision curve analysis.
• Comparisons were made against conventional surrogate insulin resistance indices.
• Sensitivity analyses corroborated the consistency of all findings.
• Multiple subgroup analyses were conducted to verify robustness.

Lower baseline estimated glomerular filtration rate (eGFR) partly mediated the association between TyG-FI and mortality.

• Lower baseline eGFR accounted for 16.45% to 26.74% of the associations between TyG-FI and mortality in exploratory mediation analyses.
• These were described as exploratory mediation analyses quantifying the proportion of mortality associations accounted for by baseline eGFR.
• The role of eGFR was examined as part of the study's exploration of mechanisms linking TyG-FI to mortality outcomes.

The study population included 11,228 adults from a nationally representative U.S. survey followed over a median of 90 months.

• Participants were aged 20–79 years from NHANES 2001–2018.
• Median follow-up was 90 months.
• There were 1,220 all-cause deaths and 379 cardiovascular deaths during follow-up.
• Restricted cubic splines were used to examine non-linear relationships between TyG-FI and outcomes.
• Survey-weighted analytical methods were applied to account for the complex sampling design.