Hally Kathryn E, Parker Olivia M, Brunton-O'Sullivan Morgane M, Harding Scott A, Larsen Peter D
Department of Surgery and Anaesthesia, The University of Otago, Wellington, New Zealand.
School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Thromb Haemost. 2021 Dec;121(12):1637-1649. doi: 10.1055/s-0041-1728763. Epub 2021 May 13.
Activation of both platelets and neutrophils can contribute to the risk of major adverse cardiovascular events (MACE) following acute myocardial infarction (AMI). Neutrophil extracellular traps (NETs) are an important product of the platelet-neutrophil axis and exaggerate vascular damage in cardiovascular disease. Additionally, activated platelets can drive NETosis and are directly linked to thromboembolic risk. Investigating the combined effect of biomarkers for NETosis and platelet activation represents a novel approach to risk prediction post-AMI. Here, we examined the utility of a composite biomarker score, inclusive of both pathways, for predicting MACE post-AMI.
In a case-control design, 100 case patients who experienced MACE within 1 year of index admission were matched in a 1:2 ratio with control patients. Serum levels of myeloperoxidase-DNA, neutrophil elastase-DNA, and citrullinated histone H3 were assayed by enzyme-linked immunosorbent assay (ELISA) as markers of NET burden. To measure platelet activation, soluble P-selectin was assayed by ELISA in parallel. Platelet and neutrophil counts were also recorded. Composite biomarker scores, inclusive of biomarkers for NETosis and platelet activation, were assessed using multivariate regression modeling. These composite biomarker scores were independent predictors of 1-year MACE. The strongest association with MACE was observed using a composite of platelet count, soluble P-selectin, and all NET markers (odds ratio: 1.94; 1.16-3.25).
Here, we demonstrate the importance of combining biomarkers of NETosis and platelet activation for risk prediction in patients with AMI. Combining biomarkers from closely linked, but distinct, biological pathways was more effective than utilizing either type of biomarker alone.
血小板和中性粒细胞的激活均可能导致急性心肌梗死（AMI）后发生主要不良心血管事件（MACE）的风险增加。中性粒细胞胞外诱捕网（NETs）是血小板-中性粒细胞轴的重要产物，会加剧心血管疾病中的血管损伤。此外，活化的血小板可促使NETosis发生，并且与血栓栓塞风险直接相关。研究NETosis生物标志物和血小板激活的联合作用代表了一种预测AMI后风险的新方法。在此，我们检验了一种包含这两种途径的复合生物标志物评分对预测AMI后MACE的效用。
在一项病例对照设计中，100例在首次入院后1年内发生MACE的病例患者与对照患者按1:2的比例进行匹配。通过酶联免疫吸附测定（ELISA）检测血清中髓过氧化物酶-DNA、中性粒细胞弹性蛋白酶-DNA和瓜氨酸化组蛋白H3的水平，作为NET负荷的标志物。同时通过ELISA检测可溶性P-选择素，以测量血小板激活情况。还记录了血小板和中性粒细胞计数。使用多变量回归模型评估包含NETosis生物标志物和血小板激活生物标志物的复合生物标志物评分。这些复合生物标志物评分是1年MACE的独立预测指标。使用血小板计数、可溶性P-选择素和所有NET标志物的组合观察到与MACE的最强关联（比值比：1.94；1.16 - 3.25）。
在此，我们证明了联合NETosis生物标志物和血小板激活生物标志物对AMI患者风险预测的重要性。将来自紧密相关但不同的生物学途径的生物标志物联合起来比单独使用任何一种生物标志物更有效。
