Cardiovasc Diabetol. 2026 Apr 24. doi: 10.1186/s12933-026-03092-5. Online ahead of print.
ABSTRACT
BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of mortality in China. The triglyceride-glucose (TyG) index and body roundness index (BRI)-have separately shown associations with CVD risk, but their interaction, as well as their combined effects and interplay with inflammatory markers remain unclear.
METHODS: We conducted a prospective cohort study using data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020. A total of 7,853 participants without pre-existing CVD were included. We examined mediation, cross-lagged path, interaction and joint association analysis to explore the interrelationships between TyG and BRI on CVD. Cox proportional hazards models and restricted cubic spline analysis, receiver operating characteristic (ROC), and weighted quantile sum (WQS) were performed to further investigate the associations between TyG, BRI, and CVD.
RESULTS: During a median follow-up of 9.0 years, 1,922 participants (24.48%) developed CVD. In fully adjusted models, baseline BRI mediated 40.14% of the association between baseline TyG and CVD risk, with an indirect effect HR of 1.053 (95% CI: 1.035-1.073). Follow-up BRI mediated 51.46% of the association between baseline TyG and CVD risk, with an indirect effect HR of 1.046 (95% CI: 1.028-1.068). Per standard deviation increase in baseline BRI led to an average increase of 0.12 standard deviation in follow-up TyG levels. A significant antagonistic interaction was observed, aligned with the finding that the combination of low TyG and high BRI presents the highest CVD risk. Additionally, WQS analysis highlights waist circumference (WC) as the most substantial contributor (weight = 0.523). Joint elevation of composite indexes (TyG-BRI and TyG + BRI) with hs-CRP further stratified CVD risk, with participants having elevated levels of all markers showing the highest risk. Composite indexes, particularly TyG + BRI, showed the highest CVD risk (HR: 1.773, 95% CI: 1.499-2.097), along with the limited discriminatory ability on CVD (AUC < 0.65).
CONCLUSION: In conclusion, our study highlights the critical role of BRI as a mediator in the relationship between TyG and CVD risk. The findings indicate that both baseline and follow-up BRI significantly contribute to the pathway linking TyG to CVD, suggesting that individuals with higher BRI are at an increased risk. The antagonistic interaction underscores the complexity of metabolic risk factors in CVD development and emphasizes the need for a multifaceted approach in risk assessment and management. Future research should focus on elucidating the biological mechanisms underlying this interaction and exploring potential interventions that target body composition and metabolic health to mitigate CVD risk in high-risk populations.
PMID:42032735 | DOI:10.1186/s12933-026-03092-5