Prognostic Value of the Neutrophil‐to‐Lymphocyte Ratio for All‐Cause Mortality in Patients With Cardiovascular–Kidney–Metabolic Stage 4

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) Stage 4 is defined by established cardiovascular disease in the setting of kidney and/or metabolic dysfunction. Despite the high risk carried by this condition, simple tools for refining prognosis are limited. The neutrophil-to-lymphocyte ratio (NLR), derived from routine differential blood counts, has been linked to outcomes in cardiovascular, renal, and critically ill populations. Whether it is prognostically informative in critically ill adults with CKM Stage 4 is not established. We investigated the relationship between NLR and all-cause mortality in this population. METHODS: Using the Medical Information Mart for Intensive Care IV (MIMIC-IV), we assembled a retrospective cohort of adults who met CKM Stage 4 criteria. For patients with multiple intensive care unit (ICU) admissions, analysis was restricted to the earliest stay. Admission NLR was derived from the first valid paired neutrophil and lymphocyte measurements recorded within 24 h. Patients were classified by NLR quartile. The prespecified primary endpoints were 30-day and 365-day all-cause mortality, with 90-day and 180-day mortality as secondary endpoints. Associations were examined using multivariable Cox regression, restricted cubic splines, subgroup analyses, sensitivity analyses, and mediation analysis. RESULTS: Among 13,602 eligible patients, mortality rose progressively across NLR quartiles at all assessed time points. After full adjustment, the hazard ratio (HR) for Q4 compared with Q1 was 2.142 (95% confidence interval [CI], 1.858-2.469) for 30-day mortality. The corresponding 365-day HR was 1.708 (95% CI, 1.543-1.891). Associations at 90 and 180 days were similar. Restricted cubic splines indicated nonlinear relationships. Results were generally stable in subgroup and sensitivity analyses. Adding NLR improved established ICU severity scores, and blood urea nitrogen (BUN) partially mediated the observed association. CONCLUSIONS: Admission NLR was independently related to higher all-cause mortality during both short- and long-term follow-up in critically ill adults with CKM Stage 4. Because it is routinely available, NLR may provide complementary information for risk stratification in this population.