Buso Giacomo, Faggin Elisabetta, Bressan Alessandro, Galliazzo Silvia, Cinetto Francesco, Felice Carla, Fusaro Michele, Erdmann Andreas, Pauletto Paolo, Rattazzi Marcello, Mazzolai Lucia
Angiology Division, Heart and Vessel Department, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
Department of Clinical and Experimental Sciences, 2a Medicina-Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia, University of Brescia, 25100 Brescia, Italy.
Biomedicines. 2023 Mar 12;11(3):866. doi: 10.3390/biomedicines11030866.
Neutrophils play a role in cardiovascular (CV) disease. However, relatively scant evidence exists in the setting of peripheral artery disease (PAD). The aims of this study were to measure biomarkers of neutrophil activation in patients with symptomatic chronic PAD compared with healthy controls, to assess their association with PAD severity, and to evaluate their prognostic value in patients with PAD. The following circulating markers of neutrophil degranulation were tested: polymorphonuclear neutrophil (PMN) elastase, neutrophil gelatinase-associated lipocalin (NGAL), and myeloperoxidase (MPO). Neutrophil extracellular traps (NETs) were quantified by measuring circulating MPO-DNA complexes. Patients with PAD underwent a comprehensive series of vascular tests. The occurrence of 6-month major adverse CV (MACE) and limb events (MALE) was assessed. Overall, 110 participants were included, 66 of which had PAD. After adjustment for conventional CV risk factors, PMN-elastase (adjusted odds ratio [OR]: 1.008; 95% confidence interval [CI]: 1.002-1.015; = 0.006), NGAL (adjusted OR: 1.045; 95%CI: 1.024-1.066; < 0.001), and MPO (adjusted OR: 1.013; 95%CI: 1.001-1.024; = 0.028) were significantly associated with PAD presence. PMN-elastase (adjusted hazard ratio [HR]: 1.010; 95%CI: 1.000-1.020; = 0.040) and MPO (adjusted HR: 1.027; 95%CI: 1.004-1.051; = 0.019) were predictive of 6-month MACE and/or MALE. MPO displayed fair prognostic performance on receiver operating characteristic (ROC) curve analyses, with an area under the curve (AUC) of 0.74 (95%CI: 0.56-0.91) and a sensitivity and specificity of 0.80 and 0.65, respectively, for a cut-off of 108.37 ng/mL. MPO-DNA showed a weak inverse correlation with transcutaneous oximetry (TcPO2) on proximal foot (adjusted ρ -0.287; = 0.032). In conclusion, in patients with symptomatic chronic PAD, enhanced neutrophil activity may be associated with an increased risk of acute CV events, rather than correlate with disease severity. Further research is needed to clarify the role of neutrophils in PAD natural history.
中性粒细胞在心血管疾病中发挥作用。然而，在外周动脉疾病（PAD）方面，相关证据相对较少。本研究的目的是测量有症状的慢性PAD患者与健康对照者中性粒细胞活化的生物标志物，评估它们与PAD严重程度的关联，并评估它们在PAD患者中的预后价值。检测了以下中性粒细胞脱颗粒的循环标志物：多形核中性粒细胞（PMN）弹性蛋白酶、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和髓过氧化物酶（MPO）。通过测量循环中的MPO-DNA复合物来定量中性粒细胞胞外诱捕网（NETs）。PAD患者接受了一系列全面的血管检查。评估了6个月时主要不良心血管（MACE）和肢体事件（MALE）的发生情况。总体而言，共纳入110名参与者，其中66名患有PAD。在对传统心血管危险因素进行校正后，PMN弹性蛋白酶（校正比值比[OR]：1.008；95%置信区间[CI]：1.002-1.015；P = 0.006）、NGAL（校正OR：1.045；95%CI：1.024-1.066；P < 0.001）和MPO（校正OR：1.013；95%CI：1.001-1.024；P = 0.028）与PAD的存在显著相关。PMN弹性蛋白酶（校正风险比[HR]：1.010；95%CI：1.000-1.020；P = 0.040）和MPO（校正HR：1.027；95%CI：1.004-1.051；P = 0.019）可预测6个月时的MACE和/或MALE。在受试者工作特征（ROC）曲线分析中，MPO显示出较好的预后性能，曲线下面积（AUC）为0.74（95%CI：0.56-0.91），对于截断值108.37 ng/mL，敏感性和特异性分别为0.80和0.65。MPO-DNA与足近端的经皮血氧饱和度（TcPO2）呈弱负相关（校正ρ -0.287；P = 0.032）。总之，在有症状的慢性PAD患者中，中性粒细胞活性增强可能与急性心血管事件风险增加有关，而非与疾病严重程度相关。需要进一步研究以阐明中性粒细胞在PAD自然病程中的作用。
