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血栓炎症与 ST 段抬高型心肌梗死的临床转归相关。

Thromboinflammation is associated with clinical outcome after ST-elevation myocardial infarction.

机构信息

Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Institute of Analytical Chemistry, University of Vienna, Vienna, Austria.

出版信息

Blood Adv. 2024 Nov 12;8(21):5581-5589. doi: 10.1182/bloodadvances.2024014273.

Abstract

Platelets are crucial in thrombus formation during ST-elevation myocardial infarction (STEMI). In addition, they also play an important role in postischemic thromboinflammation, which is determined by the interplay between activated platelets and neutrophils. The latter form neutrophil extracellular traps, which are detectable in plasma as citrullinated histone H3-deoxyribonucleic acid-DNA complexes. Prediction of the risk of recurrent events is important in precision medicine. Therefore, we investigated whether circulating thromboinflammatory markers predict clinical outcome after STEMI. We performed a prospective, multicentric, observational, all-comer study of patients with STEMI (n = 361). Thromboinflammation, measured as H3Cit-DNA complexes, was assessed on day 1 after presentation with STEMI as well as 5 days and 6 months after STEMI by enzyme-linked immunosorbent assay. Twelve months of clinical follow-up was conducted. Multivariate analysis was performed investigating which variables were independently associated with major adverse cardiac events (MACEs). Patients were aged 64 ± 12 years; 80% were male; and 40% had diabetes mellitus. Thromboinflammation was enhanced during index hospitalization compared with 6-months follow-up (137.4 ± 100.0 μg/L vs 53.7 ± 54.7 μg/L; P < .001). Additionally, patients within the highest tertile of thromboinflammation at day 1 after STEMI showed worse outcome during follow-up (hazard ratio, 2.57; 95% confidence interval, 1.72-3.85; P < .001). Receiver operating characteristic analysis revealed a cutoff value of 219.3 μg/L. In multivariate logistic regression analysis, thromboinflammation was independently associated with outcome after STEMI. To sum it up, thromboinflammation is enhanced in STEMI. It identifies patients at high risk of MACE. Therefore, thromboinflammation might be a promising target and marker in precision medicine. The trial was registered at www.clinicaltrials.gov as #NCT03539133.

摘要

血小板在 ST 段抬高型心肌梗死(STEMI)时的血栓形成中起着至关重要的作用。此外,它们在缺血后血栓炎症中也发挥着重要作用,这是由激活的血小板和中性粒细胞之间的相互作用决定的。后者形成中性粒细胞胞外诱捕网,可在血浆中作为瓜氨酸化组蛋白 H3-脱氧核糖核酸-DNA 复合物检测到。在精准医学中,预测复发事件的风险很重要。因此,我们研究了循环血栓炎症标志物是否可预测 STEMI 后的临床结局。我们对 361 例 STEMI 患者进行了前瞻性、多中心、观察性、所有患者的研究。通过酶联免疫吸附试验,在 STEMI 发作后第 1 天以及 STEMI 后 5 天和 6 个月评估血栓炎症,用 H3Cit-DNA 复合物表示。进行了 12 个月的临床随访。进行多变量分析,以研究哪些变量与主要不良心脏事件(MACEs)独立相关。患者年龄为 64±12 岁;80%为男性;40%患有糖尿病。与 6 个月随访相比,指数住院期间的血栓炎症增强(137.4±100.0μg/L 比 53.7±54.7μg/L;P<0.001)。此外,在 STEMI 后第 1 天血栓炎症处于最高三分位的患者在随访期间的结局较差(危险比,2.57;95%置信区间,1.72-3.85;P<0.001)。接受者操作特征分析显示,截断值为 219.3μg/L。在多变量逻辑回归分析中,血栓炎症与 STEMI 后的结局独立相关。综上所述,STEMI 时血栓炎症增强。它可识别出发生 MACE 的高危患者。因此,血栓炎症可能是精准医学中有前途的靶点和标志物。该试验在 www.clinicaltrials.gov 上注册为 #NCT03539133。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e44/11541696/23f598f2debf/BLOODA_ADV-2024-014273-ga1.jpg

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