Neutrophil-to-Lymphocyte Ratio and Outcomes in Patients Admitted for Acute Heart Failure (As Seen in the BLAST-AHF, Pre-RELAX-AHF, and RELAX-AHF Studies)

https://doi.org/10.1016/j.amjcard.2022.06.037Get rights and content

Previous studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) is a novel yet readily evaluable inflammatory biomarker that may be useful for determining cardiovascular prognosis during acute episodes. The study investigated the role of NLR in predicting cardiovascular (CV) outcomes in patients with acute heart failure (HF). Individual patient data from the BLAST-AHF (phase 2b study of the biased ligand of the angiotensin 2 type 1 receptor, TRV027), Pre-RELAX-AHF (phase 2b study of recombinant human relaxin-2, serelaxin), and RELAX-AHF (phase 3 study of serelaxin) randomized, placebo-controlled studies for patients with acute HF were pooled for analysis. Dyspnea visual analog scale area under the curve through day 5, worsening HF through day 5, 30-day all-cause mortality, 60-day HF/renal failure rehospitalizations or CV death, 180-day all-cause mortality, and 180-day CV death were assessed. There were several differences in the baseline characteristics of the patients divided by NLR tertile, with patients in the higher NLR having worse clinical characteristics. NLR was an independent predictor of 30-day all-cause mortality (adjusted hazard ratio [HR] per log2 NLR increment: 1.66 [1.22 to 2.25], p = 0.001), 60-day HF/renal failure rehospitalizations or CV death: 1.33 [1.12 to 1.57], p = 0.001), 180-day all-cause mortality (adjusted HR 1.27 [1.08 to 1.50], p = 0.003), and 180-day CV death (adjusted HR 1.24 [1.04 to 1.49], p = 0.018). NLR, a readily available inflammatory biomarker, was associated with independent risk for short- and long-term adverse outcomes in acute HF, surpassing traditional markers, such as natriuretic peptides.

Section snippets

Methods

An analysis was conducted from the pooled data from the BLAST-AHF, Pre-RELAX-AHF, and RELAX-AHF randomized, placebo-controlled studies for patients with acute HF. All studies were approved by local ethics committees and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from each patient who participated in these studies.

The methods and main results of BLAST-AHF (NCT01966601), Pre-RELAX-AHF (NCT00520806), and RELAX-AHF (NCT00520806) were published

Results

Baseline characteristics by NLR tertile at randomization are presented in Table 1. Overall, higher NLR was significantly associated with older age, White race, lower weight, lower body mass index, hypertension, more severe dyspnea by VAS, higher heart rate, and higher respiratory rate. There were also significant differences in recent New York Heart Association class and clinical presentations (orthopnea, rales, and dyspnea on exertion) between the NLR tertile groups. In terms of laboratory

Discussion

This post hoc analysis of results from the BLAST-AHF, Pre-RELAX-AHF, and RELAX-AHF studies combined database examined the relations between baseline levels of NLR, with the changes in dyspnea to day 5 by VAS AUC, WHF through day 5, 30-day all-cause mortality, 60-day HF/RF rehospitalizations or CV death, and 180-day all-cause mortality, and 180-day CV death. The unadjusted and adjusted analyses suggest that a higher NLR at baseline was not associated with changes in dyspnea to day 5 by VAS AUC.

Disclosures

The BLAST-AHF study was sponsored by Trevena, Inc. The Pre-RELAX-AHF and RELAX-AHF studies were sponsored by Corthera Inc., a Novartis affiliate company. No external support was provided for these analyses. Drs. Davison, Takagi, Edwards, and Cotter are employees of Momentum Research Inc. Momentum Research Inc. has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics Inc., Corteria Pharmaceuticals, Roche Diagnostics Inc., Sanofi, Windtree Therapeutics Inc.

References (29)

  • S Omiya et al.

    Cytokine mRNA degradation in cardiomyocytes restrains sterile inflammation in pressure-overloaded hearts

    Circulation

    (2020)
  • DL. Mann

    Innate immunity and the failing heart: the cytokine hypothesis revisited

    Circ Res

    (2015)
  • JS Park et al.

    Importance of prognostic value of neutrophil to lymphocyte ratio in patients with ST-elevation myocardial infarction

    Medicine (Balthimore)

    (2018)
  • KD van der Willik et al.

    Balance between innate versus adaptive immune system and the risk of dementia: A population-based cohort study

    J Neuroinflammation

    (2019)
  • View full text