Abstract
Clinical evidence indicates that innate immune cells may contribute to acute coronary syndrome (ACS). Our prospective study aimed at investigating the association of neutrophil phenotypes with ACS. 108 patients were categorized into chronic stable coronary artery disease (n = 37), unstable angina (UA) (n = 19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n = 25), and ST-Elevation Myocardial Infarction (STEMI) (n = 27). At the time of inclusion, blood neutrophil subpopulations were analysed by flow cytometry. Differential blood cell count and plasma levels of neutrophilic soluble markers were recorded at admission and, for half of patients, at six-month follow-up. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio than stable and UA patients (p < 0.0001), which normalized at six-month post-MI. Atypical low-density neutrophils were detected in the blood of the four patient groups. STEMI patients were characterized by elevated percentages of band cells compared to the other patients (p = 0.019). Multivariable logistic regression analysis revealed that plasma levels of total myeloperoxidase was associated with STEMI compared to stable (OR: 1.434; 95% CI: 1.119–1.837; P < 0.0001), UA (1.47; 1.146–1.886; p = 0.002), and NSTEMI (1.213; 1.1–1.134; p = 0.0001) patients, while increased neutrophil side scatter (SSC) signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033–14.184; p = 0.045). Hence, changes in neutrophil phenotype are concomitant to ACS.
Highlights
Increasing clinical evidence supports the existence of a link between low-grade systemic inflammation and cardiovascular (CV) risk [1]
Non-ST-Elevation Myocardial Infarction (NSTEMI) and ST-Elevation Myocardial Infarction (STEMI) patients had higher neutrophil counts than stable and unstable angina (UA) patients (p < 0.0001; NSTEMI vs. UA p = 0.012)
Plasma levels of S100A9, total and active MPO, and of nucleosomes, well-known circulating markers of neutrophil activation and neutrophil extracellular trap (NET) release that have previously been associated with CVD risk and acute coronary syndrome (ACS) [14,15,16,17], were higher in STEMI patients than in stable (S100A9: p = 0.013; total MPO: p < 0.0001; active MPO: p < 0.0001; nucleosomes: p = 0.032) and UA (S100A9: p = 0.018; total MPO: p < 0.0001; active MPO: p < 0.0001; nucleosomes: p = 0.007) patients (Figure 2A)
Summary
Increasing clinical evidence supports the existence of a link between low-grade systemic inflammation and cardiovascular (CV) risk [1]. Plasma level of high-sensitive C-reactive protein (hs-CRP) at the time of acute coronary syndrome (ACS) and its rise after the incident disease have been associated with a higher risk of major CV event [2]. Among other inflammation-related risk factors, several studies pointed to the differential white blood cell count, with a particular focus on neutrophils, lymphocytes and monocytes. Med. 2020, 9, x FOR PEER REVIEW could predicntebuotrtohpahciul-tteoa-lnydmcphhroocnyicteCrVatDio[4(N,5]L.RIn) thearessntiontgolyn,laynbeeleenvaatsesdocnieautetdrowphitihl-tCo-VlyDmbpuhtoaclystoe with shortratio (NLR)thearms naodt voenrlsyebCeVenDaossuotccioamteeds,winitchluCdVinDgbmutoartlasolitwy,itchorsohnoartr-ytearrmtearydvdeirsseeasCeV(DCAoDut)c,osmtroesk,e and heart including mfoariltuarliety,[6c]o.roCnhaarnygaersteirny dNisLeRasear(eCAsuDb)s, esqtruoeknetantod ahemarot dfaifiliucarteio[6n]. Blood Samples, Sera and Platelet Poor Plasma (PPP) Preparation, Laboratory Measurements. IL-6 and S100A9 were measured on EDTA-plasma using a Luminex assay kit (R&D Systems, Minneapolis, MN, USA) according to the manufacturer’s instructions. Hs-CRP, CK-MB (Abbott Laboratories, Wavre, Belgium) and high-sensitive troponin T (hs-TnT) (Roche, Machelen, Belgium) were measured in sera by routine immunoassays Myeloperoxidase quantity and activity were analysed on EDTA-plasma by a method adapted from Franck et al [11] using a human myeloperoxidase (MPO) Quantikine ELISA kit (R&D Systems). hs-CRP, CK-MB (Abbott Laboratories, Wavre, Belgium) and high-sensitive troponin T (hs-TnT) (Roche, Machelen, Belgium) were measured in sera by routine immunoassays
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