循环 PCSK9 与急性 ST 段抬高型心肌梗死再灌注损伤的关系。
Association of Circulating PCSK9 With Ischemia-Reperfusion Injury in Acute ST-Elevation Myocardial Infarction.
机构信息
University Clinic of Internal Medicine III, Cardiology and Angiology (C.T., M.H., I.L., F.O., S.E., T.K., A.B., B.M., S.J.R., M.R.), Medical University of Innsbruck, Austria.
University Clinic of Cardiac Surgery (C.G.-T.), Medical University of Innsbruck, Austria.
出版信息
Circ Cardiovasc Imaging. 2024 Aug;17(8):e016482. doi: 10.1161/CIRCIMAGING.123.016482. Epub 2024 Aug 20.
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; <0.001) after PCI. PCSK9 24 hours after PCI did not show any relation to intramyocardial hemorrhage, MVO, and infarct size (all >0.05). PCSK9 concentrations 48 hours post-STEMI were higher in patients with intramyocardial hemorrhage (333 versus 287 ng/mL; =0.004), MVO (320 versus 292 ng/mL; =0.020), and large infarct size (323 versus 296 ng/mL; =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%; =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.
背景
除了治疗意义外，PCSK9（脯氨酰肽链内切酶/枯草溶菌素 9）已成为一种很有前途的心血管生物标志物。PCSK9 在急性 ST 段抬高型心肌梗死（STEMI）中的确切作用尚不完全清楚。我们旨在研究 PCSK9 与经皮冠状动脉介入治疗（PCI）血运重建的 STEMI 患者的缺血再灌注损伤之间的关系，通过心脏磁共振成像来评估。
方法
在这项来自前瞻性 MARINA-STEMI（NCT04113356）注册研究的预设子研究中，我们纳入了 205 例 STEMI 患者。在 PCI 后 24 小时和 48 小时，通过免疫测定法从静脉血样中测量 PCSK9 浓度。主要终点定义为根据心脏磁共振 T2* 映射存在心肌内出血。次要成像终点为微血管阻塞（MVO）和梗死面积。临床终点为主要不良心脏事件的发生。
结果
我们观察到 PCI 后 24 小时至 48 小时（268-304ng/mL；<0.001），PCSK9 水平显著升高。PCI 后 24 小时，PCSK9 与心肌内出血、MVO 和梗死面积均无明显关系（均>0.05）。STEMI 后 48 小时，心肌内出血患者的 PCSK9 浓度较高（333 与 287ng/mL；=0.004）、MVO 患者的 PCSK9 浓度较高（320 与 292ng/mL；=0.020）和梗死面积较大的患者的 PCSK9 浓度较高（323 与 296ng/mL；=0.013）。此外，在中位随访 12 个月期间，48 小时时 PCSK9 水平>361ng/mL 的患者更有可能发生主要不良心脏事件（15%与 8%；=0.002）。
结论
在 STEMI 患者中，我们观察到 PCI 后 24 小时至 48 小时 PCSK9 显著增加。虽然 24 小时后 PCSK9 水平与心肌或微血管损伤无关，但 48 小时后 PCSK9 水平与心肌内出血、MVO 和梗死面积以及随后较差的临床结局显著相关。
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