Triglyceride-glucose index and uric acid associations with cardiovascular disease risk in middle-aged and elderly populations: findings from the China health and retirement longitudinal study.

BACKGROUND: Traditional cardiovascular disease (CVD) risk models may fail to adequately capture the interactions among metabolic factors. We evaluated the combined and mediating associations of the triglyceride-glucose (TyG) index and uric acid (UA) with incident CVD in Chinese adults.

METHODS: Using data from the nationally representative China Health and Retirement Longitudinal Study, we included 9,353 participants aged ≥ 45 years without baseline CVD or cancer, whose fasting triglycerides, glucose, and UA were measured in 2011, and who were followed up through 2020. TyG was calculated as ln [triglycerides (mg/dL) × glucose (mg/dL)/2]. Incident CVD (including myocardial infarction, coronary heart disease, angina pectoris, congestive heart failure, or stroke) was ascertained via standardized self-reported questionnaires. Cox proportional hazards models were used to quantify the relationship between TyG index/UA level, their combination categories and CVD events. Kaplan-Meier curves were used to illustrate the time-dependent association and synergistic effect of TyG index and UA on CVD-related outcomes. Age subgroup classification was used to analyze the effects of two biomarkers on CVD at different ages. Mediation analysis was conducted to assess the direct and indirect associations between two biomarkers and CVD events.

RESULTS: During the 9-year follow-up, 2505 (26.8%) individuals developed CVD, including 1745 (18.7%) cases of CHD and760 (8.1%) cases of stroke. Compared with TyG < median (8.59) and UA 4-5 mg/dL, higher TyG and higher UA were each associated with greater CVD risk (fully adjusted HR = 1.146 for TyG ≥ median and HR = 1.167 for UA > 6 mg/dL, all P < 0.05). The joint category of TyG ≥ median and UA > 6 mg/dL showed the strongest association, especially for stroke (fully adjusted HR = 2.193). Elevated TyG and UA levels jointly increased the cumulative incidence of CVD (41.1%), coronary heart disease (31.5%), and stroke (119.3%) relative to the reference group. Synergy was most evident at ages 45-59 and was not significant at ≥ 70 years. Mediation analyses supported a bidirectional pathway: TyG affected CVD via UA and UA affected CVD via TyG.

CONCLUSIONS: The TyG index and UA levels independently and synergistically increase CVD risk in middle-aged and elderly Chinese adults, with the strongest synergistic effect observed in middle-aged individuals (45-59 years). A bidirectional mediating relationship exists between the TyG index and UA in their effects on CVD. Combined assessment of the TyG index and UA may improve CVD risk stratification, supporting more refined clinical and public health interventions for CVD prevention.