A Novel Metabolic Inflammation Index for Cardiovascular Prognosis: Evidence From Three International Cohorts in Middle‐Aged and Older Adults

BACKGROUND: Chronic inflammation and insulin resistance (IR) are key drivers of cardiovascular disease (CVD); however, their joint impact on cardiovascular risk remains poorly understood. METHODS: We developed the metabolic-inflammatory index (eMII) based on estimated glucose disposal rate (eGDR) in a derivation cohort (ELSA) and evaluated its transportability in two external validation cohorts (CHARLS, HRS). Multivariate Cox regression was utilised to assess the joint impact of IR and inflammation on long-term CVD risk. RESULTS: A total of 14,168 middle-aged and older adults were included (mean age 61.68 ± 9.67 years). In fully adjusted Cox models, low eGDR, elevated hs-CRP and their combined status were all associated with increased CVD risk, with the highest risk observed in participants with both poor metabolic function and high inflammation. Exploratory mediation analysis indicated that eGDR accounted for 41.14%, 46.50% and 75.47% of the inflammation-CVD association in ELSA, CHARLS and HRS, respectively. In terms of the new index-eMII, higher eMII levels were consistently linked to elevated CVD risk across all cohorts; compared with the lowest quartile, the highest quartile showed hazard ratios of 1.66 (ELSA), 2.28 (CHARLS) and 1.83 (HRS) (all p < 0.001). Lastly, incorporating eMII into traditional risk models showed potential for improving cardiovascular risk prediction, with a more noticeable reclassification benefit observed within CHARLS. CONCLUSIONS: eMII is a cross-population predictor of CVD, highlighting metabolic impairment as a key factor through which inflammation drives cardiovascular risk. It provides a practical perspective for observing joint metabolic-inflammatory burdens in middle-aged and older adults.