Neutrophil-to-lymphocyte ratio and mortality in the United States general population

Abstract

The neutrophil-to-lymphocyte ratio (NLR) in peripheral blood reflects the balance between systemic inflammation and immunity and is emerging as a prognostic biomarker in many diseases, but its predictive role for mortality in the general population has not been investigated. We analyzed 1999-2014 National Health and Nutrition Examination Survey mortality-linked data, followed up until 2015. In participants aged > 30 with measurements of differential white blood cell counts, NLR was calculated and categorized into quartiles. Associations of increased NLR with overall or cause-specific mortality were assessed with Cox proportional hazard regression models, adjusted for potential confounders. Increased NLR was associated with overall mortality (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.10-1.17, per quartile NLR) and mortality due to heart disease (1.17, 1.06-1.29), chronic lower respiratory disease (1.24, 1.04-1.47), influenza/pneumonia (1.26, 1.03-1.54) and kidney disease (1.26, 1.03-1.54). NLR was associated with cancer mortality only in the first follow-up year (HR 1.48, 95% CI 1.11-1.98). The association with chronic lower respiratory disease mortality was stronger in individuals with prevalent lung diseases (HR 1.46, 95% CI 1.14-1.88, P_interaction = 0.01), while NLR showed positive associations with mortality from heart disease (1.21, 1.07-1.38) and cerebrovascular disease (1.30, 1.04-1.63) only among individuals without these conditions at baseline. NLR is associated with mortality overall and due to certain causes in the general population. Associations over short follow-up intervals and among individuals with conditions at baseline suggest effects of disordered inflammation and immunity on progression of those conditions, while other associations may reflect contributions to disease etiology.

Figure 1

(A) Distribution of neutrophil-to-lymphocyte ratios among individuals according to vital status on follow up date. Results are weighted using NHANES survey sample weights. The x-axis is truncated at an NLR of 13, and not included in the graph are N = 11 surviving participants (weighted percentage 0.03%) and N = 11 deceased (0.20%) with greater values. (B) Follow-up time (months) in individuals who died from specified diseases, with or without those diseases at baseline.