Joint contribution of central adiposity and frailty to cardiovascular risk in ageing populations: evidence from two longitudinal cohorts and a hospital-based cross-sectional sample

Background Central adiposity and frailty are important contributors to cardiovascular vulnerability in ageing populations. However, whether their coexistence identifies individuals with disproportionately elevated cardiovascular risk and whether this association is consistent across populations remain unclear. This study aimed to investigate the association between combined central adiposity and frailty phenotypes and incident cardiovascular disease (CVD) risk across diverse ageing populations. Methods We included participants from two nationally representative longitudinal cohorts: the China Health and Retirement Longitudinal Study (CHARLS; n = 10,156) and the English Longitudinal Study of Ageing (ELSA; n = 4,463). Participants were classified into four phenotypes according to waist circumference (WC) and relative FI level: low WC–lower FI, high WC–lower FI, low WC–higher FI, and high WC–higher FI. Incident CVD was analysed using Fine–Gray competing-risk models, with all-cause mortality considered as a competing event. Additive and multiplicative interactions between WC and FI were evaluated. A hospital-based cross-sectional sample ( n = 10,359) was additionally analysed to examine the association between WC and a laboratory-based frailty index (FI-Lab) phenotype with prevalent CVD. Results During follow-up, 1,826 incident CVD events in CHARLS and 1,213 events in ELSA were identified. Compared with low WC–lower FI phenotype, the high WC–higher FI phenotype was associated with the highest risk of incident CVD in both CHARLS (fully adjusted sHR 2.40, 95% CI 2.09–2.75) and ELSA (sHR 1.59, 95% CI 1.37–1.86). Higher FI showed consistent associations with CVD across cohorts, whereas the independent contribution of high WC was mainly observed in CHARLS. Significant additive and multiplicative interactions between WC and FI were observed in CHARLS (RERI 0.71, 95% CI 0.45–0.97; interaction sHR 1.33, 95% CI 1.10–1.61). Cross-cohort meta-analysis demonstrated a consistent association between low WC–higher FI and CVD risk (pooled sHR 1.33, 95% CI 1.19–1.48; I²=0.0%). In the hospital-based sample, the high WC–higher FI-Lab phenotype was associated with the highest prevalence of CVD (OR 2.57, 95% CI 2.09–3.15). Conclusions A combined phenotype of central adiposity and relative FI level identifies older adults at substantially increased cardiovascular risk. Higher FI represents a robust marker of cardiovascular vulnerability, whereas the contribution of central adiposity varies across populations and may interact synergistically with frailty in specific settings. The hospital-based FI-Lab analysis provided preliminary support for laboratory-based frailty assessment. Prospective studies are needed to establish its clinical utility and impact on cardiovascular outcomes. Clinical trial number Not applicable.