Prognostic significance of Absolute Neutrophil Count in Patients with Heart Failure with Preserved Ejection Fraction

Hassan, Abdalla; Zughul, Ramy; Villines, Dana

doi:10.21276/apjhs.2016.3.1.15

Cited by 6 publications

(9 citation statements)

References 21 publications

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“…More recently, neutrophilia (higher neutrophil count), lymphopenia (lower lymphocyte count), and a greater neutrophil to lymphocyte ratio (NLR) have been associated with HF severity, complications following LVAD insertion, and overall mortality in patients with various aetiologies of HF. 5 , 6 , 7 , 8 An increase in neutrophil blood count has not only been shown to correlate with the severity of coronary damage in patients with coronary artery diseases (CAD) 9 , 10 but also with the presence of heart failure. 11 , 12 Despite the prominent role of neutrophils in inducing the chronic inflammatory response in the pathogenesis of many diseases, 13 their role in the pathophysiology of heart failure and the impact of neutrophils targeted therapy remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Neutrophils pro‐inflammatory and anti‐inflammatory cytokine release in patients with heart failure and reduced ejection fraction

et al. 2021

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Aims Heart failure with reduced ejection fraction (HFrEF) is characterized by sub-clinical inflammation. Changes in selected biomarkers of inflammation concomitant with the release of pro-inflammatory and anti-inflammatory cytokines by neutrophils have not been investigated in patients with HFrEF. Methods and results Fifty-two patients, aged 68.8 ± 1.7 years, with HFrEF and left ventricular ejection fraction 28.7 ± 1.0%, and 21 healthy controls (CTL) were recruited. Twenty-five HF patients had type 2 diabetes. Venous blood samples from HF and CTL were collected once. Neutrophil-derived pro-inflammatory and anti-inflammatory cytokine levels were assessed in plasma by ELISA. Plasma biomarkers assessed included: C-reactive protein (CRP), vascular endothelial growth factor (VEGF), interleukins (IL)-6, -8, -1 receptor antagonist (-1RA), nitric oxide (NO), soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and E-Selectin (sE-Sel). Neutrophils were isolated and stimulated with various agonists to promote VEGF, IL-6, IL-8, and IL-1RA release. Compared with CTL, HFrEF patients showed a marked decrease in circulating VEGF [178.0 (interquartile range; IQR 99.6; 239.2) vs. 16.2 (IQR 9.3; 20.2) pg/mL, P ≤ 0.001] and NO [45.2 (IQR 42.1; 57.6) vs. 40.6 (IQR 30.4; 47.1) pg/mL, P = 0.0234]. All other circulating biomarkers were significantly elevated. Neutrophils isolated from patients with HFrEF exhibited a greater IL-8 release in response to LPS [1.2 ± 0.1 (CTL); 10.4 ± 1.6 ng/mL (HFrEF) and 12.4 ± 1.6 ng/mL (HFrEF and DM), P ≤ 0.001]. IL-6 release in response to LPS was not changed in HFrEF patients without diabetes, whereas it was significantly increased in patients with HFrEF and diabetes [46.7 ± 3.9 (CTL) vs. 165.8 ± 48.0 pg/mL (HFrEF),

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Section: Introductionmentioning

confidence: 99%

Neutrophils pro‐inflammatory and anti‐inflammatory cytokine release in patients with heart failure and reduced ejection fraction

et al. 2021

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“…More specifically, recruited innate immune cells have been involved in myocardial remodeling and might increase risk for adverse clinical events among HF patients. Thus, the assessment of circulating leukocytes as a proxy of myocardial remodeling is becoming an emerging area of interest to predict clinical outcomes in HF patients 6, 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Elevated circulating neutrophils is associated with higher incidence of acute decompensated HF and mortality rate in HF patients 6, 7, 19 . The role of neutrophils in myocardial repair and its impact on patient’s prognosis have been reported in HFrEF patients 6, 20 .…”

Section: Introductionmentioning

confidence: 99%

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Low density neutrophils and neutrophil extracellular traps (NETs) are new inflammatory players in heart failure

Dumont,

Neagoe,

Charles

et al. 2023

Preprint

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BackgroundHeart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) is characterized by low-grade chronic inflammation. Circulating neutrophils regroup two subtypes termed high- and low-density neutrophils (HDNs and LDNs). LDNs represent less than 2% of total neutrophil under physiological conditions, but their count increase in multiple pathologies, releasing more inflammatory cytokines and neutrophil extracellular traps (NETs).ObjectivesAssess the differential count and role of HDNs, LDNs and NETs-related activities in HF patients.MethodsHDNs and LDNs were isolated from human blood by density gradient and purified by FACS and their counts obtained by flow cytometry. NETs formation (NETosis) was quantified by confocal microscopy. Circulating inflammatory and NETosis biomarkers were measured by ELISA. Neutrophil adhesion onto human extracellular matrix (hECM) was assessed by optical microscopy.ResultsA total of 140 individuals were enrolled, including 33 healthy volunteers (HV), 41 HFrEF (19 stable patients and 22 presenting acute decompensated HF; ADHF) and 66 HFpEF patients (36 stable patients and 30 presenting HF decompensation). HDNs and LDNs counts were significantly increased up to 39% and 2740% respectively in HF patients compared to HV. In HF patients, the correlations between LDNs counts and circulating inflammatory (CRP, IL-6 and -8), Troponin T, NT-proBNP and NETosis components were all significant. In vitro, LDNs expressed more H3Cit and NETs and were more pro-adhesive, with ADHFpEF patients presenting the highest pro-inflammatory profile.ConclusionsHFpEF patients present higher levels of circulating LDNs and NETs related activities, which are the highest in the context of acute HF decompensation.Clinical PerspectiveIn comparison to HFrEF, HFpEF patients have higher levels of circulation LDNs and NETs-associated inflammatory cytokines, peaking in acute decompensated clinical condition.Furthermore, LDNs are producing more NETs and are more adhesive than HDNs, which can contribute to pro-thrombogenesis status described in HF patientsMeasurement of circulating NETs-associated biomarkers could become a novel tool to assess the the risk of acute thrombogenesis in hospitalized ADHFpEF patients.These measurements could lead to future clinical treatments using NETosis inhibitors alone or combined with NETs degradation enzymes (e.g. DNase I).At this time, additional preclinical studies are required to determine specific cell surface markers that could distinguish LDNs from HDNs in whole blood.Once available, circulating LDNs levels would be routinely measured and integrated in the complete blood count analysis to better assess patients’ inflammatory status.

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“…with a higher risk of cardiovascular events, the incidence of acute decompensated HF, and mortality rate. 7,8 The main objectives of this study were to investigate the changes in selected biomarkers, the potency of isolated neutrophils to release pro-inflammatory and anti-inflammatory cytokines in patients with HFpEF, and assess the impacts of DM on these findings.…”

mentioning

confidence: 99%

Neutrophils and Circulating Inflammatory Biomarkers in Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction

Chaar

Dumont

Vulesevic

et al. 2022

The American Journal of Cardiology

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Prognostic significance of Absolute Neutrophil Count in Patients with Heart Failure with Preserved Ejection Fraction

Cited by 6 publications

References 21 publications

Neutrophils pro‐inflammatory and anti‐inflammatory cytokine release in patients with heart failure and reduced ejection fraction

Neutrophils pro‐inflammatory and anti‐inflammatory cytokine release in patients with heart failure and reduced ejection fraction

Low density neutrophils and neutrophil extracellular traps (NETs) are new inflammatory players in heart failure

Neutrophils and Circulating Inflammatory Biomarkers in Diabetes Mellitus and Heart Failure With Preserved Ejection Fraction

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