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

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. Keywords: modified cardiometabolic index, cardiovascular-kidney-metabolic syndrome, all-cause mortality, cardiovascular mortality, diabetes mellitus, competing risks model, cohort study, risk prediction