The association between neutrophil-to-lymphocyte ratio and all-cause and cardiovascular specific mortality in patients with diabetes and prediabetes complicated by cardiometabolic syndrome

Background The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has shown prognostic value in chronic diseases, but its association with mortality in cardiometabolic syndrome (CMS) patients with dysglycemia (diabetes or prediabetes) remains underexplored. This study sought to assess the predictive value of the NLR for all-cause and cardiovascular specific mortality in this high-risk population. Methods Using data from the National Health and Nutrition Examination Survey (NHANES, 1999–2018), we analyzed 4,833 CMS patients with dysglycemia. NLR was calculated from complete blood counts. We employed a Cox regression model adjusted for machine learning-selected covariates to evaluate the association between NLR and mortality. Restricted cubic spline (RCS) models were applied to analyze the nonlinear dose-response relationship between NLR and mortality risk. Time-dependent receiver operating characteristic (ROC) curves were utilized to assess predictive performance. Finally, subgroup analyses were conducted to examine differences across various population strata. Results Over a median follow-up, higher NLR quartiles (Q4 vs. Q1) exhibited worse metabolic profiles and higher all-cause (27.44% vs. 13.73%) and cardiovascular specific mortality (11.55% vs. 3.25%). NLR demonstrated linear (all-cause mortality) and nonlinear (cardiovascular specific mortality) dose-response mortality associations. Adjusted models revealed each unit NLR increase independently predicted 12% (HR 1.12, 95% CI 1.07–1.17) and 13% (HR 1.13, 95% CI 1.07–1.20) higher risks for all-cause and cardiovascular specific mortality, respectively. NLR showed superior predictive accuracy versus conventional insulin resistance indices, though with declining accuracy over time (all-cause mortality: 1-year area under the curve (AUC) = 0.70 to 5-year = 0.64; cardiovascular specific mortality: 0.75 to 0.67), demonstrating stronger short-term prognostic value. Conclusion NLR is an independent predictor of short- and long-term mortality in dysglycemic CMS patients, offering superior discriminative utility compared to traditional metabolic markers. Its cost-effectiveness and accessibility support its clinical adoption for risk stratification in this population.