Association of the C-reactive protein-triglyceride-glucose (CTI) index and its central obesity-modified derivatives with incident cardiometabolic multimorbidity: results from two prospective cohorts in China and England

Background Central obesity exacerbates cardiometabolic multimorbidity (CMM) susceptibility through insulin resistance and inflammation. We investigated the longitudinal association of C-reactive protein–triglyceride–glucose (CTI)-related indices—which integrate these mechanisms with abdominal obesity measurements—with incident CMM in middle-aged and older adults. Methods Utilizing a discovery cohort of 6,616 subjects (aged ≥ 45) from the China Health and Retirement Longitudinal Study (CHARLS), Boruta and LASSO regressions identified CTI–waist-to-height ratio (CTI-WHtR) and CTI–waist circumference (CTI-WC) as principal exposures. Findings were validated in the English Longitudinal Study of Ageing (ELSA, n = 2,682). We evaluated associations and prognostic utility across both cohorts using Cox models, restricted cubic splines, and discrimination/reclassification metrics, including area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI). Competing risk, weighted quantile sum (WQS) regression, and mediation analyses were conducted in CHARLS to explore mechanistic contributions. Results During median follow-ups of 6.62 (CHARLS) and 7.65 (ELSA) years, 734 and 382 incident CMM events occurred, respectively. In CHARLS, central obesity-modified indices exhibited the strongest associations (CTI-WHtR: HR = 4.59, 95%CI: 3.41–6.17; CTI-WC: HR = 4.38, 95%CI: 3.29–5.83) and optimal predictive performance (AUCs up to 0.739). By comparison, the unmodified CTI demonstrated the optimal predictive value in ELSA (HR = 2.53, 95%CI: 1.76–3.64; AUC = 0.746). All these optimal indices outperformed traditional TyG-related metrics, further confirmed by significant improvements in continuous NRI, IDI (all P < 0.05), and DCA net benefits across cohorts. In CHARLS, WQS regression highlighted the substantial contributions of the central obesity components within their respective indices (WHtR: 39.2%; WC: 37.3%), while C-reactive protein, systolic blood pressure, and estimated pulse wave velocity partially mediated the CTI-WHtR–CMM relationship. Conclusion The CTI index and its central obesity-modified derivatives (CTI-WHtR and CTI-WC) are robust predictors of incident CMM, consistently outperforming traditional TyG-related metrics. Notably, the necessity for central obesity modification is population-specific: it is crucial for optimizing risk stratification in Asian populations (CHARLS), whereas the unmodified CTI suffices as the optimal predictor in European populations (ELSA), highlighting the need for tailored CMM early identification strategies in clinical practice.