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载脂蛋白(a)水平升高的冠心病患者经前蛋白转化酶枯草溶菌素 9 抑制剂治疗前后动脉壁功能和形态学特性的预测因素。

Predictors of functional and morphological arterial wall properties in coronary artery disease patients with increased lipoprotein (a) levels before and after treatment with proprotein convertase subtilisin-kexin type 9 inhibitors.

机构信息

Department of Vascular Diseases, University Medical Centre Ljubljana, 1000, Ljubljana, Slovenia.

Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

出版信息

Cardiovasc Ultrasound. 2023 Aug 14;21(1):15. doi: 10.1186/s12947-023-00313-9.


DOI:10.1186/s12947-023-00313-9
PMID:37580777
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10424345/
Abstract

BACKGROUND: In addition to proatherogenic properties, lipoprotein (a) (Lp(a)) has also pro-inflammatory, antifibrinolytic and prothrombogenic features. The aim of the current study was to identify the predictors of functional and morphological properties of the arterial wall in patients after myocardial infarction and increased Lp(a) levels at the beginning and after treatment with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors. METHODS: Seventy-six post-myocardial infarction patients with high Lp(a) levels were included in the study. Ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima-media thickness (c-IMT) and pulse wave velocity (PWV) were performed initially and after 6 months of treatment. At the same time points lipids, Lp(a), inflammatory and hemostasis markers were measured in blood samples. RESULTS: In linear regression model FMD significantly correlated with age at first myocardial infarction (β = 0.689; p = 0.022), high-sensitivity C-reactive protein (β = -1.200; p = 0.009), vascular cell adhesion protein 1 (VCAM-1) (β = -0.992; p = 0.006), overall coagulation potential (β = 1.428; p = 0.014) and overall hemostasis potential (β = -1.473; p = 0.008). c-IMT significantly correlated with age at first myocardial infarction (β = 0.574; p = 0.033) and Lp(a) (β = 0.524; p = 0.040). PWV significantly correlated with systolic blood pressure (β = 0.332; p = 0.002), tumor necrosis factor alpha (β = 0.406; p = 0.002), interleukin-8 (β = -0.315; p = 0.015) and plasminogen activator inhibitor 1 (β = 0.229; p = 0.031). After treatment FMD reached statistical significance only in univariant analysis with systolic blood pressure (r = -0.286; p = 0.004) and VCAM-1 (r = -0.229; p = 0.024). PWV and c-IMT correlated with age (r = 0.334; p = 0.001 and r = 0.486; p < 0.0001, respectively) and systolic blood pressure (r = 0.556; p < 0.0001 and r = 0.233; p = 0.021, respectively). CONCLUSIONS: Our results suggest that age, systolic blood pressure, Lp(a) levels and other biochemical markers associated with Lp(a) are predictors of functional and morphological properties of the arterial vessel wall in post-myocardial patients with high Lp(a) levels initially. However, after 6 months of treatment with PCSK9 inhibitors only age and systolic blood pressure seem to be predictors of these properties. TRIAL REGISTRATION: The protocol for this study was registered with clinicaltrials.gov on November, 3 2020 under registration number NCT04613167.

摘要

背景:载脂蛋白(a)[Lp(a)]除了具有动脉粥样硬化形成作用外,还具有炎症、抗纤维蛋白溶解和促血栓形成作用。本研究旨在确定心肌梗死后患者和 Lp(a)水平升高的患者的动脉壁功能和形态特征的预测因子,以及在开始治疗和治疗后应用前蛋白转化酶枯草溶菌素 9(PCSK9)抑制剂时的这些特征。

方法:将 76 名高 Lp(a)水平的心肌梗死后患者纳入研究。最初和治疗 6 个月后进行肱动脉血流介导的扩张(FMD)、颈动脉内膜中层厚度(c-IMT)和脉搏波速度(PWV)的超声测量。同时在血液样本中测量血脂、Lp(a)、炎症和止血标志物。

结果:在线性回归模型中,FMD 与首次心肌梗死时的年龄(β=0.689;p=0.022)、高敏 C 反应蛋白(β=-1.200;p=0.009)、血管细胞黏附蛋白 1(VCAM-1)(β=-0.992;p=0.006)、总体凝血潜能(β=1.428;p=0.014)和总体止血潜能(β=-1.473;p=0.008)显著相关。c-IMT 与首次心肌梗死时的年龄(β=0.574;p=0.033)和 Lp(a)(β=0.524;p=0.040)显著相关。PWV 与收缩压(β=0.332;p=0.002)、肿瘤坏死因子-α(β=0.406;p=0.002)、白细胞介素-8(β=-0.315;p=0.015)和纤溶酶原激活物抑制剂 1(β=0.229;p=0.031)显著相关。治疗后,FMD 仅在收缩压的单变量分析中具有统计学意义(r=-0.286;p=0.004)和 VCAM-1(r=-0.229;p=0.024)。PWV 和 c-IMT 与年龄(r=0.334;p=0.001 和 r=0.486;p<0.0001,分别)和收缩压(r=0.556;p<0.0001 和 r=0.233;p=0.021,分别)显著相关。

结论:我们的研究结果表明,年龄、收缩压、Lp(a)水平和其他与 Lp(a)相关的生化标志物是初始高 Lp(a)水平的心肌梗死后患者动脉血管壁功能和形态特征的预测因子。然而,在 6 个月的 PCSK9 抑制剂治疗后,只有年龄和收缩压似乎是这些特征的预测因子。

试验注册:该研究的方案于 2020 年 11 月 3 日在 clinicaltrials.gov 上注册,注册号为 NCT04613167。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10424345/f60e341cb4d5/12947_2023_313_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10424345/f60e341cb4d5/12947_2023_313_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/617d/10424345/f60e341cb4d5/12947_2023_313_Fig1_HTML.jpg

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