Front Endocrinol (Lausanne). 2026 Sep 30;17:1952253. doi: 10.3389/fendo.2026.1952253. eCollection 2026.
ABSTRACT
BACKGROUND: The triglyceride-glucose (TyG) index and its derivatives are cost-effective markers of insulin resistance and cardiovascular risk. However, the comparative predictive value of baseline levels, cumulative exposure, and annual mean changes in TyG-related indices remains unclear. This study aimed to systematically compare the predictive performance of multiple dimensions of TyG-related indices for cardiovascular events in rural older adults with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3.
METHODS: This cohort study enrolled 4,169 participants aged ≥65 years with no history of cardiovascular events. Longitudinal data from annual standardized health examinations under the National Basic Public Health Services Project were used to calculate baseline, cumulative exposure, and annual mean change values of TyG-related indices. Associations, dose-response relationships, and predictive performance were assessed via accelerated failure time models, restricted cubic spline analyses, time-dependent receiver operating characteristic analyses, and model fit statistics. Linear mixed-effects models were applied to delineate longitudinal trajectories of these indices. Sensitivity analyses were further conducted to verify the robustness of the main findings.
RESULTS: During 6 years of follow-up, 822 cardiovascular events were documented. Cardiovascular risk increased progressively with advancing CKM syndrome stages (P = 0.004). Baseline and cumulative TyG-WC and TyG-WHtR were consistently and strongly associated with incident cardiovascular events (all P < 0.001), with cumulative measures demonstrating slightly stronger associations. Dose-response analyses revealed a linear relationship between TyG and cardiovascular events, whereas TyG-BMI, TyG-WC, and TyG-WHtR exhibited nonlinear associations. In terms of association strength, most annual mean change measures were not significantly associated with outcomes, only TyG-BMI showed a weak association(P = 0.033) and was the only indicator with a statistically significant time-to-CVD interaction in longitudinal trajectory analysis. Nevertheless, all annual mean change indicators generally demonstrated poorer predictive performance than baseline and cumulative indicators for cardiovascular events. Among all indices, baseline and cumulative TyG-WC showed the optimal predictive performance across follow-up periods, and baseline TyG-WC had predictive utility comparable to cumulative TyG-WC. Sensitivity analyses further confirmed the robustness of these key findings.
CONCLUSION: Baseline and cumulative TyG-related indices demonstrated stronger associations with cardiovascular events compared with annual mean changes, suggesting that sustained metabolic exposure is more clinically informative than short-term fluctuation. Baseline and cumulative TyG-WC demonstrated relatively better predictive performance and, especially baseline measure, may serve as a simple and low-cost auxiliary tool for cardiovascular risk stratification in resource-constrained primary care settings, though it should not replace conventional cardiovascular risk-assessment instruments.
PMID:42818901 | PMC:PMC13624300 | DOI:10.3389/fendo.2026.1952253