Association of Cardiometabolic Index with Mortality Risk in Early-Stage Cardiovascular-Kidney-Metabolic Syndrome and Its Potential Role in Metabolically Unhealthy Phenotypes: Evidence from NHANES 2007-2018.

Abstract

Background: The cardiometabolic index (CMI) has emerged as a composite marker of metabolic dysfunction. However, its prognostic value for mortality in early-stage cardiovascular-kidney-metabolic (CKM) syndrome remains unclear. This study aimed to evaluate the association between CMI and mortality risk in individuals with CKM stages 0-3, and to assess whether CMI provides incremental predictive value over body mass index (BMI).

Methods: This retrospective cohort study included 11,280 adults from the National Health and Nutrition Examination Survey 2007-2018 with CKM stages 0-3. CMI was calculated as (triglycerides/HDL-C) × waist-to-height ratio. Mortality outcomes were ascertained through linkage with the National Death Index through December 31, 2019. Survey-weighted Cox proportional hazards regression and restricted cubic splines were used to examine associations. Kaplan-Meier survival curves with log-rank tests were employed to compare survival probabilities across CMI-BMI discordance phenotypes. Random survival forest models compared the predictive performance of CMI versus BMI.

Results: During a median follow-up of 6.2 years, 623 all-cause deaths and 159 cardiovascular deaths occurred. In fully adjusted models, participants in the highest CMI quartile had significantly elevated risks of all-cause mortality [hazard ratio (HR) = 1.55, 95% confidence intervals (CI): 1.15-2.09] and cardiovascular mortality (HR = 1.91, 95% CI: 1.05-3.46) compared with the lowest quartile. Restricted cubic spline analyses revealed significant nonlinear associations, with inflection points at CMI of 2.51 for all-cause mortality and 1.06 for cardiovascular mortality. In the overweight subgroup and among diabetic patients, CMI demonstrated superior risk stratification compared with BMI. Notably, metabolically obese normal-weight individuals exhibited significantly worse survival than metabolically healthy obese individuals.

Conclusions: CMI is independently associated with all-cause and cardiovascular mortality in early-stage CKM syndrome, with evidence of threshold effects. CMI may serve as a valuable complementary tool to BMI for identifying high-risk individuals, particularly among those with metabolically unhealthy phenotypes masked by normal weight status.