Abstract
BACKGROUND: Systemic inflammation plays a central role in atrial fibrillation (AF). The neutrophil-to-lymphocyte ratio (NLR) is a simple hematological index that has been shown to be associated with prognosis in different pathologies. HYPOTHESIS: The NLR is associated with an increased risk of adverse events in patients with AF. METHODS: We included a prospective cohort of AF patients who started vitamin K antagonists (VKAs) therapy between July 2016 and June 2018. NLR was assessed at baseline and classified into three categories: low (< 3), moderate (3-5), and high (> 5). During a 2-year follow-up period, all cardiovascular deaths, all-cause deaths, and net clinical outcomes (NCO; either ischemic stroke/transient ischemic attack, major bleeding or all-cause death), were recorded. RESULTS: A total of 1050 patients were included (51.4% women; median age 77 years). NLR was available in 936 patients: 507 (54.2%) had low NLR (< 3), 239 (25.5%) had moderate NLR (3-5), and 190 (20.3%) had high NLR (> 5). The primary endpoint was significantly increased in the high NLR category (p = 0.002 for cardiovascular death; p < 0.001 for all-cause mortality, and p < 0.001 for NCO), with higher IRRs (all p < 0.001). Multivariate Cox regression analyses showed that high NLR was independently associated with an increased risk of cardiovascular death (aHR: 2.02; 95% CI: 1.04-3.92), all-cause mortality (aHR: 2.51; 95% CI: 1.58-3.97), and NCO (aHR: 1.99; 95% CI: 1.37-2.87), compared to low NLR. CONCLUSIONS: In this prospective AF cohort receiving VKAs, elevated NLR was significantly associated with an increased risk of adverse clinical outcomes. NLR has independent prognostic value beyond other classical risk factors.