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循环前蛋白转化酶枯草杆菌蛋白酶/克新9型浓度、凝血酶原时间与心血管结局的关联:一项前瞻性队列研究。

Association of circulating proprotein convertase subtilisin/kexin type 9 concentration, prothrombin time and cardiovascular outcomes: a prospective cohort study.

作者信息

Peng Jia, Liu Ming-Ming, Liu Hui-Hui, Guo Yuan-Lin, Wu Na-Qiong, Dong Qian, Qian Jie, Dou Ke-Fei, Zhu Cheng-Gang, Li Jian-Jun

机构信息

Cardiometabolic Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No 167 BeiLiShi Road, XiCheng District, Beijing, 100037, China.

出版信息

Thromb J. 2021 Nov 22;19(1):90. doi: 10.1186/s12959-021-00344-0.

Abstract

BACKGROUND

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered to have multiple roles in the development of atherosclerosis, which is recently reported to participate in the thrombotic process. We aimed to examine the relationship between PCSK9 concentration, coagulation indexes and cardiovascular events.

METHODS

A total of 2293 consecutive patients with angina-like chest pain and without lipid-lowering drugs treatment were enrolled and followed up for major adverse cardiovascular events (MACEs). Circulating PCSK9 concentration was determined by ELISA. The routine coagulation tests including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time were performed. The associations between PCSK9 concentration, routine coagulation indicators and MACEs were analyzed.

RESULTS

Patients with high PCSK9 levels had lower PT and APTT levels (all p <  0.05). However, PCSK9 concentration was only independently and negatively correlated with PT (β = - 0.115, p <  0.001). During a mean of 38.3 months, 186 (8.1%) MACEs were occurred. Multiple Cox regression analysis indicated high PCSK9 or low PT levels as risk factors related to MACEs. When the prognosis was analyzed by the combination of PCSK9 and PT levels, patients with high PCSK9 and low PT had higher incidence of MACEs compared to those with low PCSK9 and high PT.

CONCLUSIONS

Our study firstly suggested that PCSK9 concentration was negatively correlated with plasma levels of PT. Furthermore, high PCSK9 and low PT were associated with MACEs and the combination of PCSK9 with PT had an addictive effect on predicting cardiovascular outcomes in patients with chest pain, which was useful for further subdivision of cardiovascular risks.

摘要

背景

前蛋白转化酶枯草溶菌素/kexin 9型(PCSK9)被认为在动脉粥样硬化的发展中具有多种作用,最近有报道称其参与血栓形成过程。我们旨在研究PCSK9浓度、凝血指标与心血管事件之间的关系。

方法

共纳入2293例连续的类似心绞痛胸痛患者,这些患者未接受降脂药物治疗,并对主要不良心血管事件(MACE)进行随访。通过酶联免疫吸附测定法(ELISA)测定循环PCSK9浓度。进行常规凝血试验,包括活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)和凝血酶时间。分析PCSK9浓度、常规凝血指标与MACE之间的关联。

结果

PCSK9水平高的患者PT和APTT水平较低(所有p < 0.05)。然而,PCSK9浓度仅与PT呈独立负相关(β = -0.115,p < 0.001)。在平均38.3个月的时间里,发生了186例(8.1%)MACE。多因素Cox回归分析表明,PCSK9水平高或PT水平低是与MACE相关的危险因素。当结合PCSK9和PT水平分析预后时,与PCSK9水平低且PT水平高的患者相比,PCSK9水平高且PT水平低的患者MACE发生率更高。

结论

我们的研究首次表明,PCSK9浓度与血浆PT水平呈负相关。此外,PCSK9水平高和PT水平低与MACE相关,且PCSK9与PT的联合对预测胸痛患者的心血管结局具有累加效应这对于进一步细分心血管风险很有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa64/8607723/c6c2440c0d69/12959_2021_344_Fig1_HTML.jpg

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