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Multicenter Study
. 2025 Feb;48(2):e70102.
doi: 10.1002/clc.70102.

The Neutrophil-to-Lymphocyte Ratio Is an Independent Inflammatory Biomarker for Adverse Events in Patients With Atrial Fibrillation: Insights From the Murcia AF Project II (MAFP-II) Cohort Study

Eva Soler-Espejo  1 , Francisco Marín  2 , Raquel López-Gálvez  2 , María Pilar Ramos-Bratos  2 , María Sánchez-Villalobos  1 , María Asunción Esteve-Pastor  2 , Gregory Y H Lip  3   4 , José Miguel Rivera-Caravaca  3   5 , Vanessa Roldán  1
Affiliations
Multicenter Study

The Neutrophil-to-Lymphocyte Ratio Is an Independent Inflammatory Biomarker for Adverse Events in Patients With Atrial Fibrillation: Insights From the Murcia AF Project II (MAFP-II) Cohort Study

Eva Soler-Espejo et al. Clin Cardiol. 2025 Feb.

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.

Keywords: atrial fibrillation; cardiovascular death; major bleeding; mortality; neutrophil‐to‐lymphocyte ratio; stroke.

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Conflict of interest statement

Gregory Y. H. Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi‐Sankyo, Anthos. No fees are received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co‐PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalized management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for the management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU's Horizon Europe Research & Innovation program. José Miguel Rivera‐Caravaca is a consultant for Idorsia Pharmaceuticals Ltd. Francisco Marín is a consultant and speaker for Boehringer‐Ingelheim and BMS/Pfizer. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier survival curves for the primary endpoints. Blue line = low neutrophil‐to‐lymphocyte ratio (NLR) (< 3). Green line = moderate NLR (3–5). Red line = high NLR (> 5).
Figure 2
Figure 2
Restricted cubic spline of neutrophil‐to‐lymphocyte ratio at baseline on the X‐axis and adjusted hazard ratio and 95% confidence interval on the Y‐axis. X‐axes represent quantitative increases of NLR, Y‐axes represent adjusted hazard ratios of the primary endpoints and 95% confidence intervals. CI, confidence interval; HR, hazard ratio; NLR, neutrophil‐to‐lymphocyte ratio.
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