Cumulative inflammatory index and the risk of cardiometabolic multimorbidity: a prospective cohort study among middle-aged and older adults in China

BACKGROUND: Multiple inflammatory markers are central determinants of insulin resistance and cardiovascular inflammation, closely associated with cardiometabolic multimorbidity (CMM). However, the evidence regarding the impact of their long-term elevation on CMM remains limited. METHODS: We analyzed data from 4,602 CHARLS participants free of cardiometabolic multimorbidity (CMM) at the 2011 baseline, with follow-up through 2018 to assess CMM incidence. Six cumulative inflammatory indices (Cumulative C-reactive protein-triglyceride-glucose index, Cumulative C-reactive protein, Cumulative white blood cell count, cumulative inflammatory score, Cumulative ratio of C-reactive protein to high-density lipoprotein, Cumulative high-density lipoprotein) were evaluated for associations with CMM risk. Each cumulative index was calculated as the product of the average value of an inflammatory marker across the first and third study waves and the total exposure duration. Multivariable Cox proportional hazards regression, restricted cubic spline regression, subgroup analyses, and interaction tests were performed to assess risk associations, nonlinear relationships, and heterogeneity. To validate the applicability of these indices in diverse populations, we conducted external validation using another large-scale longitudinal cohort-the English Longitudinal Study of Ageing (ELSA) database. RESULTS: cumCRP, cumWBC, cumCRP/HDL, and the cumulative inflammatory score were significantly positively associated with CMM risk, while cumHDL showed a negative linear relationship with CMM outcomes. Among them, cumCTI exhibited the strongest association with CMM incidence, with a hazard ratio (HR) of 2.19 (95% confidence interval [CI]: 1.61-2.98) compared to the first quartile. Area under the curve (AUC) values in three confounder-adjusted models were 0.619, 0.641, and 0.726, respectively. Additionally, several cumulative inflammatory indicators showed multiplicative interactions with gender, dyslipidemia, and body mass index (BMI) in relation to CMM risk. External validation in the ELSA database demonstrated that cumCTI remained the strongest predictor of CMM incidence among all cumulative inflammatory indices, with a receiver operating characteristic (ROC) curve area under the curve (AUC) of 0.75 and a hazard ratio (HR) of 3.28 (95% CI: 1.52-7.91). CONCLUSION: This study demonstrates associations between six cumulative inflammatory indices and CMM risk. Individuals with elevated C-reactive protein-triglyceride-glucose index (CTI) require heightened vigilance for the development of CMM. Long-term monitoring of CTI fluctuations may facilitate early prevention and mitigation of CMM.