Nutr Metab Cardiovasc Dis. 2026 Apr 18:104761. doi: 10.1016/j.numecd.2026.104761. Online ahead of print.
ABSTRACT
BACKGROUND AND AIM: Cardiovascular-kidney-metabolic (CKM) syndrome is a disorder of growing global burden. This study aims to investigate the association between the hemoglobin-to-red cell distribution width ratio (HRR) and mortality in individuals with CKM, and to evaluate the mediating role of estimate glomerular filtration rate (eGFR).
METHODS AND RESULTS: We analyzed 7189 CKM patients from NHANES 2011-2018. The association between HRR and mortality was assessed using Cox regression, with nonlinearity examined by restricted cubic splines (RCS). Survival differences were plotted with Kaplan-Meier curves. Model robustness was tested via stratified and sensitivity analyses, and a mediation analysis evaluated the role of eGFR. The cohort comprised 7189 participants with 632 documented deaths during follow-up, including 120 cardiovascular-specific events. Across full adjusted models, higher HRR levels showed inverse correlations with mortality (P < 0.05). Per 1-unit increase in HRR, multivariable-adjusted risks decreased by 93% for both all-cause (HR: 0.07, 95% CI: 0.04-0.14) and cardiovascular mortality (HR: 0.07, 95% CI: 0.02-0.28). The highest HRR tertile demonstrating markedly lower mortality risks versus reference groups (all-cause: HR: 0.51; cardiovascular: HR: 0.51). Stratified analysis and sensitivity analysis demonstrated the stability of the model. RCS analysis confirmed a U-shaped relationship between HRR and all-cause mortality, while a linear relationship was observed between HRR and cardiovascular mortality. Mediation analysis showed eGFR accounted for 2.6% and 4.5% of the associations of HRR with all-cause and cardiovascular mortality, respectively.
CONCLUSIONS: A higher HRR may be associated with reduced mortality in patients with CKM syndrome, and this association is partially mediated by eGFR.
PMID:42115080 | DOI:10.1016/j.numecd.2026.104761