Joint effects and mediating mechanisms of body roundness index and biological aging on the risk of incident cardiovascular disease: a nationally representative prospective cohort study

Abstract

Body roundness index (BRI) and biological aging are critical drivers of cardiovascular disease (CVD). However, their joint pathogenic effects and underlying mechanisms in the development of CVD remain elusive. This study aims to investigate the independent and joint effects of BRI and biological age acceleration on the risk of incident CVD among middle-aged and older adults, evaluate their incremental predictive value, and elucidate the mediating role of biological aging within the obesity-CVD pathological pathway. This longitudinal study included 6,389 middle-aged and older participants free of CVD at baseline from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2020). Multivariate Cox proportional hazards models and restricted cubic splines (RCS) were employed to assess the associations between exposure factors and incident CVD risk. Incremental predictive value was evaluated by calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Furthermore, a bootstrapping-based mediation analysis was applied to explore pathogenic mechanisms. Over a median follow-up of 8.9 years, 1,407 (22.0%) incident cardiovascular disease (CVD) events were identified. Elevated BRI and biological age acceleration independently increased the risk of incident CVD, BioAge acceleration showed a significant non-linear association, while BRI demonstrated a predominantly linear relationship. Compared to the reference group (low BRI and decelerated aging), individuals with concurrent high BRI and accelerated aging faced the highest risk of incident CVD (HR = 1.50, 95% CI: 1.28–1.75). Integrating these two indices into the baseline clinical risk model yielded a highly significant improvement in CVD risk reclassification (NRI = 0.067, P = 0.029; IDI = 0.0043, P = 0.002). Mediation analysis indicated that biological aging partially mediated the positive association between elevated BRI and CVD risk (ACME = 0.084, 95% CI: 0.027–0.143, P < 0.001; ADE = 0.804, 95% CI: 0.349–1.257, P < 0.001), accounting for 9.1% of the total effect, while the reverse pathway was also statistically significant, likely reflecting the cross-sectional correlation between the two measures. Elevated Body Roundness Index (BRI) and biological age acceleration exert joint pathogenic effects on the risk of incident CVD. Biological age acceleration partially mediates the pathological cascade connecting elevated BRI to incident CVD. The joint assessment of BRI and biological age acceleration in primary care settings can efficiently identify hidden high-risk individuals often missed by traditional clinical models, thereby significantly optimizing early risk stratification for CVD.