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.