Abstract
OBJECTIVES: The emerging triglyceride-glucose (TyG) related index has attracted attention as a promising predictor of various cardiometabolic conditions. However, their prospective association with different stages of cardiovascular-renal metabolic (CKM) syndrome is still not fully established, and it remains unclear whether TyG related parameters have prognostic effects on mortality outcomes of CKM syndrome. METHODS: The data were derived from the China Health and Retirement Longitudinal Study (CHARLS), and which were determined by the use of a standardised questionnaire during follow-up. TyG and its related parameters (TyG-body mass index, TyG-waist circumference, TyG-waist to height ratio, and TyG-a body shape index (TyG-ABSI) were calculated. Multivariate Cox regression analysis was used to analyze hazard ratios (HRs) and 95% confidence intervals (CI), and Kaplan-Meier survival curve was used to analyze the associations of TyG-ABSI with all-cause mortality and cardiovascular mortality in patients with CKM syndrome. Additionally, the multivariate adjusted restricted cubic spine was employed to examine the dose-response relationship. Mediation analysis was conducted to assess whether white blood cell (WBC) and C-reactive protein (CRP) mediated the associations. Subgroup analyses and interaction tests were conducted to evaluate the risk within various demographics. The National Health and Nutrition Examination Survey (NHANES) was used as validation to improve the reliability of the study results. RESULTS: The study enrolled 11,235 participants with CKM syndrome from the CHARLS database, during the median follow-up of 5 years, a total of 747 (6.65%) all-cause mortality and 84 (0.75) cardiovascular mortality occurred. TyG-ABSI was associated with CKM syndrome (OR 1.55; 95% CI 1.35-1.79). Furthermore, among patients with CKM syndrome, TyG-ABSI was association with all-cause mortality (HR 1.14; 95% CI 1.04-1.35). In which continuous TyG-ABSI were converted to classified variable (tertile), compared to those with T1 group, the risk of advanced CKM syndrome was found to be 2.41-fold higher in those with T3 group (OR 2.41; 95% CI 1.18-3.20). Additionally, individuals in the T3 group had a 55% increased risk of all-cause mortality (HR 1.55; 95% CI 1.10-2.18). The mediation analysis results suggested that the relationship between TyG-ABSI and all-cause mortality risk is partially mediated by WBC, and CRP, the proportion of mediation were 15.16% and 11.83%. Additionally, analyses of 15,054 participants from the NHANES database indicated a significant positive association between TyG-ABSI and all-cause mortality and cardiovascular mortality among individuals diagnosed with CKM syndrome during the 10 years follow-up. CONCLUSION: Higher TyG-ABSI is associated with an increased risk of advanced CKM syndrome and mortality. It further emphasizes the role of TyG-ABSI in the management of CKM syndrome stages and the risk of all-cause mortality and cardiovascular mortality.