Association of Modified Cardiometabolic Index with Cardiovascular-Kidney-Metabolic Syndrome Staging, All-Cause Mortality, and Cardiovascular Mortality: A Population-Based Cohort Study

Abstract Objective To investigate the association of the modified cardiometabolic index (MCMI) with cardiovascular-kidney-metabolic (CKM) syndrome staging, all-cause and cardiovascular mortality, and compare its predictive performance with traditional indices. Methods This prospective cohort study included 5,189 adults with CKM syndrome (stages 0–4) from NHANES 1999–2018 (median follow-up 10.4 years). Associations were assessed using polynomial/ordinal logistic regression, Cox models, and restricted cubic splines. Mediation analysis explored diabetes’ role. Competing risks (Fine-Gray), E-values, and sensitivity analyses ensured robustness. Predictive performance was compared using C-index and AUC. Results MCMI showed a “decelerating increase” nonlinear association with CKM staging (adjusted OR=3.90, 95%CI: 3.38–4.50). For all-cause mortality, MCMI>3.5 exhibited a threshold effect (Q4 vs Q1: HR=1.412, 1.046–1.907); RCS curves identified MCMI<3.5 as a safety interval. For cardiovascular mortality, MCMI showed a fluctuating nonlinear pattern with low-risk (3.0–3.5) and high-risk (<2.5 or >4.0) intervals. Diabetes mediated 45.5% of MCMI-cardiovascular mortality risk (total HR=1.374, indirect HR=1.141). Competing risks revealed substantial underestimation of true effects (Q4 vs Q1 sHR=3.25, trend P<0.001). MCMI remained independently associated with all-cause mortality after extensive adjustments (HR=1.22, 1.05–1.40); E-values (1.73/1.29) indicated robustness. MCMI demonstrated superior predictive performance over CMI and TyG (mean AUC difference 0.0243). Conclusions MCMI is an independent predictor of CKM progression and mortality. Its cardiovascular mortality risk is predominantly mediated by diabetes. MCMI>3.5 may serve as a clinical cut-off, outperforming traditional metabolic indices for CKM risk stratification.