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脂蛋白(a)在心梗围手术期及早期的变化轨迹及前蛋白转化酶枯草溶菌素 9 抑制剂的影响。

The Trajectory of Lipoprotein(a) During the Peri- and Early Postinfarction Period and the Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition.

机构信息

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Washington University in St. Louis, St. Louis, Missouri.

出版信息

Am J Cardiol. 2022 May 15;171:1-6. doi: 10.1016/j.amjcard.2022.01.058. Epub 2022 Mar 21.

Abstract

Lipoprotein(a), or Lp(a), levels and the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on Lp(a) during the peri-infarction and early postinfarction period are not well characterized. This study aimed to describe the trajectory of Lp(a), as well as the effect of PCSK9 inhibition on that trajectory during the peri-infarction and early postinfarction period. Lp(a) levels were obtained within 24 hours of hospital admission as well as within 24 hours of hospital discharge and at 30 days from 74 participants who presented with a NSTEMI (troponin I >5 ng/ml) or with a STEMI and were enrolled in 2 randomized, double-blind trials of evolocumab and placebo (Evolocumab in Acute Coronary Syndrome [EVACS I]; ClinicalTrials.gov, NCT03515304 and Evolocumab in Patients With STEMI [EVACS II]; ClinicalTrials.gov Identifier: NCT04082442). There was a significant increase from the pretreatment level in the placebo-treated patients, from 64 (41,187) nmol/L to 80 (47, 172) nmol/L at hospital discharge and to 82 (37, 265) at 30 days. This was primarily driven by the results from participants with high Lp(a) at hospital admission (>75 nmol/L) in whom the median increase was 28% as compared with a 10% increase in those with pretreatment Lp(a) of <75 nmol/L. In contrast, there was no significant change from the pretreatment level in the evolocumab-treated patients regardless of pretreatment Lp(a) levels. In conclusion, Lp(a) rises during the peri-infarction and early postinfarction period in patients with acute myocardial infarction. The increase was prevented by a single dose of subcutaneous evolocumab given within 24 hours of hospital admission.

摘要

脂蛋白(a)或 Lp(a) 水平以及在梗死后和早期梗死后期间前蛋白转化酶枯草溶菌素/克那霉 9(PCSK9)抑制对 Lp(a) 的影响尚未得到很好的描述。本研究旨在描述 Lp(a) 的轨迹,以及在梗死后和早期梗死后期间 PCSK9 抑制对该轨迹的影响。74 名患有非 ST 段抬高型心肌梗死(肌钙蛋白 I >5ng/ml)或 ST 段抬高型心肌梗死的患者在入院后 24 小时内以及出院后 24 小时内和 30 天内获得了 Lp(a) 水平,这些患者参加了 2 项随机、双盲、安慰剂对照的依洛尤单抗研究,即急性冠状动脉综合征中的依洛尤单抗研究(EVACS I);ClinicalTrials.gov,NCT03515304 和 ST 段抬高型心肌梗死患者中的依洛尤单抗研究(EVACS II);ClinicalTrials.gov 标识符:NCT04082442)。与入院时相比,安慰剂组患者的 Lp(a) 水平从治疗前的 64(41,187)nmol/L 显著升高至出院时的 80(47,172)nmol/L,30 天时升高至 82(37,265)nmol/L。这主要是由于入院时 Lp(a)较高(>75nmol/L)的参与者的结果所致,其中中位数增加了 28%,而治疗前 Lp(a)<75nmol/L 的参与者增加了 10%。相比之下,依洛尤单抗治疗组患者的 Lp(a)水平在治疗前没有显著变化,无论治疗前的 Lp(a)水平如何。总之,急性心肌梗死后患者在梗死后和早期梗死后期间 Lp(a) 水平升高。单次皮下注射依洛尤单抗可在入院后 24 小时内预防这种增加。

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