What does this research mean for the field?

Peripheral-to-central adiposity distribution indices independently predict all-cause mortality and improve prognostic discrimination beyond BMI in individuals with cardiovascular-kidney-metabolic syndrome stages 0 to 3. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

March 1, 2026Therapeutic Advances in Endocrinology and MetabolismOpen Access

Association and prognostic value of adiposity distribution indices for all-cause mortality in cardiovascular-kidney-metabolic syndrome stages 0–3: a nationwide study

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Why the study?

Obesity drives cardiovascular-kidney-metabolic syndrome, but BMI fails to reflect body fat distribution and its associated prognostic heterogeneity.

Structured PICO

Population

5,907 adults (aged ≥20 years) with early and intermediate stages of cardiovascular-kidney-metabolic (CKM) syndrome (stages 0-3), drawn from the U.S. NHANES 1999-2006 cohort. Exclusion criteria included CKM stage 4 (established cardiovascular or end-stage kidney disease), missing anthropometric measurements, or lack of mortality follow-up.

Outcome

All-cause mortality ascertained through linkage to the National Death Index (NDI) at median 195 months follow-uphard clinical

Indices reflecting peripheral-to-central adiposity provide superior prognostic value for all-cause mortality compared to BMI in individuals with early to intermediate cardiovascular-kidney-metabolic syndrome.

Limitations

Complete-case analysis may introduce residual selection bias
Low peripheral circumferences may partly reflect unmeasured sarcopenia or aging-related frailty (reverse causation cannot be completely ruled out)
Adiposity indices were assessed solely at baseline, preventing the evaluation of dynamic changes
Excluding CKM stage 4 restricts the external validity to preclinical populations
Recall bias from self-reported covariates, unmeasured confounders, and restriction to a U.S. cohort limit broader generalizability

Implication

May refine mortality risk stratification in early CKM using fat distribution indices; leaves open incremental value over BMI in prospective studies.

Abstract

Background: Cardiovascular-kidney-metabolic syndrome (CKM) is a major public health challenge. While obesity is a central driver of CKM, body mass index (BMI) fails to adequately reflect body fat distribution and its associated prognostic heterogeneity. Objectives: To evaluate the prognostic value of emerging anthropometric indices reflecting fat distribution in predicting all-cause mortality risk among individuals in the early and intermediate stages of CKM (stages 0-3). Design: A population-based retrospective cohort study utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006, with mortality linkage follow-up through 2019. Methods: We analyzed 5907 adults with CKM stages 0-3. Eleven adiposity indices were evaluated using four machine learning algorithms (LASSO-Cox, RSF-Boruta, RSF, survival XGBoost) to identify key mortality predictors. Statistical analyses incorporated multivariable Cox proportional hazards regression, restricted cubic splines, false discovery rate (FDR) correction for multiple testing, and a sensitivity analysis across the entire CKM continuum (stages 0-4). Results: < 0.05). TCWR and CWR showed linear inverse trends, whereas AWR and SWR exhibited nonlinear threshold effects. These associations persisted across BMI subgroups and remained robust in the full CKM continuum subanalysis. The combined index model yielded improved discriminative ability (AUC = 0.769) compared to single indices (TCWR AUC = 0.731) and conventional BMI-based models, providing higher net clinical benefit. Conclusion: Peripheral-to-central adiposity indices are strong predictors of mortality in CKM stages 0-3, providing prognostic information beyond BMI and serving as practical tools for early risk stratification. Future studies should evaluate their dynamic changes and validate their applicability across diverse populations.