Joint and mediated associations of triglyceride-glucose index and body roundness index with cardiometabolic multimorbidity: a nationwide prospective cohort study

Cardiometabolic multimorbidity (CMM), defined as the presence of at least two of the following conditions: type 2 diabetes mellitus, heart disease, or stroke, represents a growing burden in aging populations. The triglyceride-glucose (TyG) index and body roundness index (BRI) are accessible markers of insulin resistance and visceral adiposity, respectively. This study aimed to investigate their independent, joint, nonlinear, and mediated associations with incident CMM. This prospective cohort study included 7,886 Chinese adults aged ≥ 45 years from the China Health and Retirement Longitudinal Study (CHARLS) who were free of CMM at baseline. Participants were classified into four groups based on the median TyG (8.6) and BRI (4.0) values: low TyG and low BRI, high TyG and low BRI, low TyG and high BRI, and high TyG and high BRI. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines and two-piecewise Cox regression assessed nonlinear associations. Mediation, subgroup, sensitivity, cumulative-exposure, and K-means–based longitudinal pattern analyses were also performed. Over a maximum follow-up of 9 years, 818 participants developed CMM. Higher TyG and BRI were each independently associated with CMM (TyG: HR = 1.55, 95% CI 1.33–1.80; BRI: HR = 1.70, 95% CI 1.45–1.99; both P < 0.001). Compared with the low TyG and low BRI group, those with both high TyG and high BRI had the highest risk (HR = 2.41, 95% CI 1.94–2.99; P < 0.001). Nonlinear associations were observed, with inflection points at approximately TyG = 8.3 and BRI = 2.3. BRI statistically accounted for 18.4% of the TyG–CMM association, and TyG accounted for 13.3% of the BRI–CMM association. The findings were supported by sensitivity and longitudinal exposure analyses. Higher TyG and BRI were independently and jointly associated with an increased risk of CMM. Exploratory mediation analyses suggested potential interrelationships between insulin resistance and visceral adiposity in relation to CMM. These findings provide complementary evidence for the potential value of TyG and BRI in CMM risk assessment. Not applicable.