Association of Circulating PCSK9 With Ischemia-Reperfusion Injury in Acute ST-Elevation Myocardial Infarction.

IF 6.5 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation: Cardiovascular Imaging Pub Date : 2024-08-01 Epub Date: 2024-08-20 DOI:10.1161/CIRCIMAGING.123.016482

Christina Tiller, Magdalena Holzknecht, Ivan Lechner, Fritz Oberhollenzer, Sebastian von der Emde, Thomas Kremser, Can Gollmann-Tepeköylü, Agnes Mayr, Axel Bauer, Bernhard Metzler, Sebastian J Reinstadler, Martin Reindl

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引用次数: 0

Abstract

Background: Beyond therapeutic implications, PCSK9 (proprotein convertase subtilisin/kexin 9) has emerged as a promising cardiovascular biomarker. The exact role of PCSK9 in the setting of acute ST-elevation myocardial infarction (STEMI) is incompletely understood. We aimed to investigate the association of PCSK9 with ischemia-reperfusion injury, visualized by cardiac magnetic resonance imaging, in patients with STEMI revascularized by primary percutaneous coronary intervention (PCI).

Methods: In this prespecified substudy from the prospective MARINA-STEMI (NCT04113356) registry, we included 205 patients with STEMI. PCSK9 concentrations were measured from venous blood samples by an immunoassay 24 and 48 hours after PCI. The primary end point was defined as presence of intramyocardial hemorrhage according to cardiac magnetic resonance T2* mapping. Secondary imaging end points were the presence of microvascular obstruction (MVO) and infarct size. The clinical end point was the occurrence of major adverse cardiac events.

Results: We observed a significant increase in PCSK9 levels from 24 to 48 hours (268-304 ng/mL; P<0.001) after PCI. PCSK9 24 hours after PCI did not show any relation to intramyocardial hemorrhage, MVO, and infarct size (all P>0.05). PCSK9 concentrations 48 hours post-STEMI were higher in patients with intramyocardial hemorrhage (333 versus 287 ng/mL; P=0.004), MVO (320 versus 292 ng/mL; P=0.020), and large infarct size (323 versus 296 ng/mL; P=0.013). Furthermore, patients with increased PCSK9 levels >361 ng/mL at 48 hours were more likely to experience major adverse cardiac events (15% versus 8%; P=0.002) during a median follow-up of 12 months.

Conclusions: In patients with STEMI, a significant increase in PCSK9 was observed from 24 to 48 hours after PCI. While PCSK9 levels after 24 hours were not related to myocardial or microvascular injury, PCSK9 after 48 hours was significantly associated with intramyocardial hemorrhage, MVO, and infarct size as well as worse subsequent clinical outcomes.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier; NCT04113356.

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循环 PCSK9 与急性 STEV 心肌梗死缺血再灌注损伤的关系

背景：除了治疗意义外，PCSK9（proprotein convertase subtilisin/kexin 9）已成为一种有前途的心血管生物标志物。目前还不完全清楚 PCSK9 在急性 ST 段抬高型心肌梗死（STEMI）中的确切作用。我们的目的是研究通过初级经皮冠状动脉介入治疗（PCI）进行血运重建的 STEMI 患者中，PCSK9 与心脏磁共振成像显示的缺血再灌注损伤的关系：在这项来自前瞻性 MARINA-STEMI （NCT04113356）登记的预设子研究中，我们纳入了 205 名 STEMI 患者。PCI术后24小时和48小时用免疫测定法测定静脉血样本中的PCSK9浓度。根据心脏磁共振 T2* 图谱，主要终点定义为是否存在心肌内出血。次要成像终点为是否存在微血管阻塞（MVO）和梗塞大小。临床终点是重大心脏不良事件的发生率：我们观察到，从 24 小时到 48 小时，PCSK9 的水平明显升高（268-304 ng/mL；PP>0.05）。心肌内出血（333 对 287 ng/mL；P=0.004）、MVO（320 对 292 ng/mL；P=0.020）和大面积梗死（323 对 296 ng/mL；P=0.013）患者在经胸膜后 48 小时的 PCSK9 浓度较高。此外，在中位随访12个月期间，48小时时PCSK9水平升高>361纳克/毫升的患者更有可能发生重大心脏不良事件（15%对8%；P=0.002）：在 STEMI 患者中，PCI 后 24 至 48 小时内 PCSK9 水平显著升高。虽然24小时后的PCSK9水平与心肌或微血管损伤无关，但48小时后的PCSK9与心肌内出血、MVO和梗死面积以及更差的后续临床预后显著相关：URL：https://www.clinicaltrials.gov；唯一标识符；NCT04113356。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation: Cardiovascular Imaging 医学-核医学

CiteScore

6.30

自引率

2.70%

发文量

225

审稿时长

6-12 weeks

期刊介绍： Circulation: Cardiovascular Imaging, an American Heart Association journal, publishes high-quality, patient-centric articles focusing on observational studies, clinical trials, and advances in applied (translational) research. The journal features innovative, multimodality approaches to the diagnosis and risk stratification of cardiovascular disease. Modalities covered include echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging and spectroscopy, magnetic resonance angiography, cardiac positron emission tomography, noninvasive assessment of vascular and endothelial function, radionuclide imaging, molecular imaging, and others. Article types considered by Circulation: Cardiovascular Imaging include Original Research, Research Letters, Advances in Cardiovascular Imaging, Clinical Implications of Molecular Imaging Research, How to Use Imaging, Translating Novel Imaging Technologies into Clinical Applications, and Cardiovascular Images.