Neutrophil-to-Lymphocyte Ratio: Link to Congestion, Inflammation, and Mortality in Outpatients with Heart Failure

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) may be a useful marker of inflammation, but its associations with clinical characteristics, signs of congestion and outcome in patients with chronic heart failure (HF) are unknown. METHODS AND RESULTS: We enrolled 4702 ambulatory patients with HF and either left ventricular systolic dysfunction or high N-terminal pro-B-type natriuretic peptide (NTproBNP) (≥125 ng/L). Compared with those in the lowest quartile of NLR (≤2.05), patients in the highest quartile (≥4.10) were older, had higher NTproBNP, and were more likely to have HF with reduced left ventricular ejection fraction (HFrEF), atrial fibrillation and to be treated with loop diuretics. In 813 patients with detailed echocardiographic assessment, lymphocyte count correlated inversely with NTproBNP (r = -0.31) and markers of congestion [left atrial volume index (r = -0.25), inferior vena cava diameter (r = -0.24)]; neutrophil count correlated positively with high-sensitivity C-reactive protein (hsCRP) (r = 0.31, P < 0.001). During a median follow-up of 54 (29-100) months, 3015 (64%) patients died. In models adjusted for NTproBNP and HsCRP, higher NLR [hazard ratio (HR):1.05; 95% confidence interval (CI) 1.03-1.06] and neutrophil count (HR:1.07; 95%CI 1.04-1.10) were associated with higher mortality rates; higher lymphocyte count (HR:0.88; 95%CI 0.82-0.95) was associated with lower risk (all P < 0.001). CONCLUSIONS: Low lymphocyte count is associated with more congestion and high neutrophil count with more inflammation, which may explain why a greater NLR is associated with a poorer prognosis. For patients with heart failure, NLR or its components could be useful for risk stratification or for monitoring evolving risk, but might also be therapeutic targets.