Abstract
BACKGROUND: While the Cardiometabolic Index (CMI) serves as a novel marker for assessing adipose tissue distribution and metabolic function, its prognostic utility for cardiovascular disease (CVD) events remains incompletely understood. This investigation sought to elucidate the predictive capabilities of CMI for cardiovascular outcomes and explore underlying mechanistic pathways to establish a comprehensive risk prediction framework. METHODS: The study encompassed 7,822 individuals from a national health and retirement longitudinal cohort, with participants stratified by CMI quartiles. Following baseline characteristic comparisons and CVD incidence rate calculations, we implemented multiple Cox regression models to assess CMI's cardiovascular risk prediction capabilities. For nomogram construction, we utilized an ensemble machine learning framework, combining Boruta algorithm-based feature selection with Random Forest (RF) and XGBoost analyses to determine key predictive parameters. RESULTS: Throughout the median follow-up duration of 84 months, we documented 1,500 incident CVD cases, comprising 1,148 cardiac events and 488 cerebrovascular events. CVD incidence demonstrated a positive gradient across ascending CMI quartiles. Multivariate Cox regression analysis, adjusting for potential confounders, confirmed a significant association between CMI and CVD risk. Notably, mediation analyses revealed that hypertension and glycated hemoglobin (HbA1c) potentially serve as mechanistic intermediaries in the CMI-CVD relationship. Sex-stratified analyses suggested differential predictive patterns between gender subgroups. Given CMI's robust and consistent predictive capability for stroke outcomes, we developed a machine learning-derived nomogram incorporating five key predictors: age, CMI, hypertension status, high-sensitivity C-reactive protein (hsCRP) and renal function (measured as serum creatinine). The nomogram demonstrated strong discriminative ability, achieving areas under the receiver operating characteristic curve (AUC) of 0.76 (95% CI: 0.56-0.97) and 0.74 (95% CI: 0.66-0.81) for 2-year and 6-year stroke prediction, respectively. CONCLUSIONS: Our findings establish CMI as a significant predictor of cardiovascular events in the aging population, with the relationship partially mediated through hypertension and insulin resistance pathways. The validated nomogram, developed using longitudinal data from a substantial elderly cohort, incorporates CMI to enable preclinical risk stratification, supporting timely preventive strategies.