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: This study included 6,498 participants from the China Health and Retirement Longitudinal Study and 2,455 from the English Longitudinal Study of Ageing, all free of diabetes, heart disease, and stroke at baseline. Incident CMM was defined as the occurrence of at least two of these diseases during follow-up. CTI-waist circumference (CTI-WC) and CTI-waist-to-height ratio (CTI-WHtR) were prespecified as principal exposures, with CTI, triglyceride-glucose index (TyG), and corresponding obesity-related derivatives as comparators. Death before CMM was treated as a competing event. Associations and prediction were assessed using Fine-Gray models, cumulative incidence functions, restricted cubic splines, time-dependent area under the curve, C-statistic, net reclassification improvement, integrated discrimination improvement, and calibration metrics. RESULTS: During median follow-up periods of 7.00 and 9.58 years, 303 and 255 participants developed incident CMM in the Chinese and English cohorts, respectively. In the Chinese cohort, each 1-standard deviation increase in CTI-WC and CTI-WHtR was associated with higher CMM risk (CTI-WC: subdistribution HR = 1.59, 95% CI 1.44-1.75; CTI-WHtR: subdistribution HR = 1.59, 95% CI 1.44-1.76), and the highest quartile had approximately fourfold higher risk than the lowest quartile. In the English cohort, associations were weaker but directionally consistent, with CTI-WC remaining significant per 1-standard deviation increment (1.18, 1.03-1.35). In the Chinese cohort, CTI-WC and CTI-WHtR yielded the highest 7-year area under the curve values (0.693 and 0.692), and CTI-WC showed the largest reclassification improvement. Calibration and sensitivity analyses supported model stability. CONCLUSIONS: Prespecified CTI-WC and CTI-WHtR were associated with incident CMM after accounting for competing mortality. Integrating inflammatory-metabolic burden with central adiposity may improve CMM risk stratification, especially in the Chinese cohort.