Long-term cumulative exposure and two-time-point patterns of the C-reactive protein–triglyceride–glucose index and cardiometabolic multimorbidity: a prospective cohort study with exploratory adiposity analyses

Abstract

Cardiometabolic multimorbidity (CMM) is increasingly prevalent in ageing populations and confers substantial clinical and societal burdens. The C-reactive protein–triglyceride–glucose index (CTI) integrates inflammatory and metabolic information, but evidence linking cumulative and two-time-point CTI patterns to incident CMM and the role of adiposity in exploratory pathway analyses remains limited. We included 5,778 participants aged ≥ 45 years who were free of CMM at baseline. Exposures were baseline CTI in 2012, cumulative CTI (cuCTI) from 2012 to 2015, and two-time-point CTI pattern groups derived from repeated measurements. Incident CMM was assessed in 2018. Multivariable logistic regression models were pooled across multiple imputations, and restricted cubic splines examined dose–response relationships. Incremental discrimination and reclassification were evaluated using C-statistics, continuous net reclassification improvement, and integrated discrimination improvement. Exploratory mediation analyses assessed adiposity indices. Incident CMM occurred in 333 participants (5.8%). In fully adjusted models, higher baseline CTI and greater cumulative CTI exposure were independently associated with higher odds of incident CMM (baseline CTI per IQR: OR 1.545, 95% CI 1.344–1.776; cuCTI per IQR: OR 1.651, 95% CI 1.429–1.907; both P  < 0.001). Two-time-point pattern analyses indicated higher odds among participants with a Stable High pattern than among those with a Persistent Low pattern (OR 3.078, 95% CI 2.169–4.369; P  < 0.001). CTI measures showed incremental apparent discrimination and reclassification within the study sample. In exploratory mediation analyses, BMI statistically accounted for 18.5% (95% CI 9.5%–32.2%) and 16.9% (95% CI 8.5%–28.7%) of the associations of baseline CTI and cuCTI with incident CMM, respectively. Higher cumulative CTI and a persistently elevated two-time-point CTI pattern were associated with incident CMM. CTI measures showed incremental apparent discrimination and reclassification within the study sample, while exploratory mediation analyses indicated that adiposity indices statistically accounted for part of the observed associations. 1. To extend previous evidence on CTI by showing its association with cardiometabolic multimorbidity, a clinically important outcome that better reflects the clustering of cardiometabolic diseases in ageing populations. 2. To show that persistently high CTI and greater cumulative CTI burden were associated with higher odds of cardiometabolic multimorbidity, highlighting the potential relevance of long-term CTI exposure. 3. To provide exploratory evidence that adiposity indices may statistically account for part of the observed associations between CTI and cardiometabolic multimorbidity. Not applicable.