Association of neutrophil-to-lymphocyte ratio with all-cause and cardiovascular mortality among cardiovascular-kidney-metabolic syndrome: a national cross-sectional study

The neutrophil-to-lymphocyte ratio (NLR) as inflammatory biomarker across cardiovascular outcomes. However, its relationship with all-cause and cardiovascular mortality in cardiovascular-kidney-metabolic (CKM) syndrome remains poorly characterized. We analyzed 7,929 CKM patients from National Health and Nutrition Examination Survey (NHANES) (2011–2018), with mortality follow-up through 2019. Cox proportional hazards models and restricted cubic splines (RCS) assessed NLR-mortality relationships. Survival disparities were quantified through Kaplan-Meier estimates. Sensitivity and stratification analyses were used to demonstrate the stability of the relationship. The receiver operating characteristic curve (ROC) analysis was conducted to access the predictive ability of NLR for survival. Mediation analysis explored estimated glomerular filtration rate (eGFR)-mediated effects.The cohort comprised 7,929 participants with 473 documented deaths during follow-up, including 125 cardiovascular-specific events. Elevated NLR independently predicted higher all-cause mortality (HR=1.13, 95%CI:1.09–1.17) and cardiovascular mortality (HR=1.17,1.11–1.24). RCS revealed a U-shaped NLR-all-cause mortality relationship (inflection: NLR=1.26, P for nonlinear=0.016), contrasting with linear cardiovascular mortality association (P for nonlinear =0.378). The highest NLR tertile demonstrating markedly higher mortality risks [all-cause mortality: HR (95CI%)1.40 (1.09, 1.81); cardiovascular mortality: HR (95CI%) 2.17 (1.24, 3.81)]. Sensitivity analysis and subgroup analyses were conducted to prove the stability of the model. ROC analysis demonstrated that the NLR had area under the curve (AUC) values of 0.651 and 0.703 for predicting all-cause mortality and cardiovascular mortality, respectively, showing superior predictive value compared to individual neutrophil or lymphocyte counts alone. Mediation analysis identified that eGFR mediated 1.7% of the NLR-all-cause mortality association and 1.6% of the cardiovascular mortality relationship. Elevated NLR levels were independently associated with increased risks of both all-cause mortality and cardiovascular mortality in patients with CKM syndrome. Moreover, these findings underscore the potential clinical utility of NLR to refine the detection of mortality in CKM population.