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, Pinteraction = 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.