Long-term metabolic–adiposity burden and cardiovascular risk: the cumTyG–WHtR in Chinese adults

BACKGROUND: Evidence on the relationship between a long-term cumulative metric that couples the triglyceride-glucose index (TyG) with the waist‒to-height ratio (WHtR) (cumTyG‒WHtR) and incident cardiovascular disease (CVD), particularly when integrated with obesity phenotypes, remains limited. METHODS: We analyzed 4,254 middle-aged and older adults from the China Health and Retirement Longitudinal Study (CHARLS), with a median follow-up of approximately 3 years. Covariates were selected via the Boruta algorithm. Cox proportional hazards models were used to assess the associations between the cumTyG-WHtR and incident CVD. Restricted cubic splines (RCSs) were used to evaluate nonlinearity and dose-response. Effect modification was examined via interaction terms and stratified analyses, and robustness was assessed via multiple sensitivity analyses. Exploratory associational decomposition using nonparametric percentile bootstrap resampling (1,000 iterations) was performed to estimate the proportion of the total association between cumTyG-WHtR and CVD that was statistically accounted for by mean arterial pressure (MAP). RESULTS: During follow-up, 587 incident CVD events occurred (cumulative incidence 13.80%), with the incidence increasing across quartiles of cumTyG-WHtR (Q1-Q4: 9.21%, 13.26%, 14.29%, 18.44%). In fully adjusted models, each 1-unit increase in cumTyG-WHtR (continuous) was associated with a 5.2% higher CVD risk (hazard ratio 1.052, 95% confidence interval 1.011-1.094). RCS revealed no evidence of nonlinearity (P for nonlinearity = 0.790), indicating a near-linear, monotonic dose-response. A significant age interaction was observed (P for interaction = 0.025), with stronger associations in participants aged 45-59 years. The findings were consistent across the sensitivity analyses. In an exploratory associational decomposition (not a causal mediation analysis), MAP statistically accounted for a significant proportion of the total association, with an indirect association estimate of 0.005 (95% CI, 0.002-0.008; p < 0.001)-a small absolute effect but in this decomposition accounting for 20.3% of the total association. CONCLUSIONS: In this cohort of middle-aged and elderly individuals, a higher cumulative TyG - WHtR was positively associated with the incidence of CVD. This association showed an approximately linear trend, and it was more significant in the population aged 45 to 59. In an exploratory associational decomposition, MAP statistically accounted for a portion of the total association. This hypothesis-generating finding requires confirmation in future studies with stronger causal designs.