Abstract
BACKGROUND: Cardiovascular-Kidney-Metabolic (CKM) syndrome, encompassing metabolic dysfunction, chronic kidney disease, and cardiovascular disease (CVD), represents a growing global health challenge. Body Roundness Index (BRI) is an index representing viscera obesity, and its prospective association with CVD across CKM stages and mediation by insulin resistance remain unexamined. OBJECTIVE: The aim of the study was to explore the association between BRI and CVD among the population of CKM syndrome stage 0-3, and discover the potential mediation of insulin resistance. METHODS: This prospective cohort study included 7,214 participants from the China Health and Retirement Longitudinal Study (CHARLS). BRI was calculated using waist circumference and height. CKM stages (0-3) were classified according to the American Heart Association criteria. CVD was defined as new-onset myocardial infarction, angina, coronary heart disease, heart failure, or other physician-diagnosed cardiac events during follow-up and was reported by participants. Cox models adjusted for demographics and metabolic factors assessed BRI-CVD associations. Restricted cubic splines tested nonlinearity, and mediation analysis quantified the contribution of TyG index. RESULTS: Among participants (mean age 59.8 ± 9.4 years, 52.9% female), each 1-unit BRI increase elevated CVD risk by 12.2% (HR = 1.122, 95% CI:1.080-1.166). The highest BRI quartile (vs. lowest) showed 58% higher CVD risk (HR = 1.585, 95% CI:1.351-1.859). A linear dose-response relationship was observed (P nonlinear > 0.05). Stronger relationship between BRI and CVD was observed in CKM stage 1-2. TyG index mediated 22.7% of the BRI-CVD association (P = 0.008). CONCLUSIONS: BRI positively linear associated with CVD, especially in early CKM syndrome population. Insulin resistance mediated the BRI-CVD association. The findings highlight BRI's potential for early risk stratification and the multifactorial pathophysiology linking adiposity to CVD.