Rapid Improvement of Coronary Endothelial Function With PCSK9 Inhibition in People With HIV Is Associated With Reduced Lipoprotein (a) and Not LDL-cholesterol.
Rapid Improvement of Coronary Endothelial Function With PCSK9 Inhibition in People With HIV Is Associated With Reduced Lipoprotein (a) and Not LDL-cholesterol.
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HIV 感染者通过抑制 PCSK9 快速改善冠状动脉内皮功能与脂蛋白 (a) 降低有关，而不是与 LDL 胆固醇降低有关。
DOI：
10.1161/circimaging.123.015693
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Leucker,ThorstenM
中科院分区：
文献类型：
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作者：
Harb,Tarek;Ziogos,Efthymios;Schär,Michael;Brown,ToddT;Lai,Shenghan;Gerstenblith,Gary;Hays,AllisonG;Leucker,ThorstenM
冠状动脉内皮功能障碍是冠状动脉粥样硬化发展的既定驱动因素，而冠状动脉内皮功能异常（CEF）是不良心血管事件的独立预测因子。磁共振成像的进步使得通过测量等长握力运动（一种内皮依赖性应激源）引起的冠状动脉横截面积的变化来量化CEF成为可能。健康的冠状动脉通过血管舒张反应，因此测量横截面积的增加;在内皮功能障碍的存在下，没有观察到变化或反常的血管收缩。1这种非侵入性方法可以评估可能改善CEF的干预措施的有效性。人类免疫缺陷病毒（HIV）感染与加速动脉粥样硬化有关。LDL-C（LDL-胆固醇）和Lp（a）（脂蛋白[a]）升高均与心血管风险独立相关，并在PCSK 9（前蛋白转化酶枯草杆菌蛋白酶/kexin 9型）抑制后降低。2我们以前报道过，用单克隆抗体evoloclavin抑制PCSK 9可以改善HIV感染者的CEF（注册：URL：https：//www.evoloclavin）。ClinicalTrials. gov;唯一标识符：NCT 03500302）。3本研究对19例HIV感染者中的15例进行了血清Lp（a）和LDL-C的检测，以探讨Lp（a）和LDL-C的变化与CEF变化的关系。和用于进行支持本研究结果的研究的材料可在合理要求下从相应作者处获得。该研究得到了约翰霍普金斯医学机构审查委员会的批准，所有参与者都提供了知情的书面同意书。在开始evolocumab（420 mg皮下注射，每4周一次）治疗前和治疗后6周，对CEF进行磁共振成像扫描。所有参与者均接受抗逆转录病毒治疗，血浆HIV RNA ≤ 27拷贝/mL。使用GraphPad Prism 9.5进行统计分析。0和SAS 9.4。使用Fisher精确检验比较分类变量。使用Shapiro-Wilk检验对数据进行正态性检验。分别对正态分布和偏态数据进行参数和非参数检验，以比较PCSK 9抑制前基线和随访时的配对Lp（a）、LDL-C和CEF测量值。采用广义估计方程分析CEF与Lp（a）、LDL-C之间的纵向相关性。
Coronary endothelial dysfunction is an established driver for the development of coronary atherosclerosis, and abnormal coronary endothelial function (CEF) is an independent predictor of adverse cardiovascular events. Advances in magnetic resonance imaging make it possible to quantify CEF by measuring changes in the coronary cross-sectional area in response to isometric handgrip exercise, an endothelial-dependent stressor. Healthy coronaries respond by vasodilatation and thus an increase in cross-sectional area is measured; no change or paradoxical vasoconstriction is seen in the presence of endothelial dysfunction. 1 This noninvasive method allows assessment of the effectiveness of interventions that may improve CEF. Human immunodeficiency virus (HIV) infection is associated with accelerated atherosclerosis. Both elevated LDL-C (LDL-cholesterol) and Lp (a)(lipoprotein [a]) are independently associated with cardiovascular risk and are reduced following PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition. 2 We previously reported that PCSK9 inhibition with the monoclonal antibody evolocumab improved CEF in people with HIV (REGISTRATION: URL: https://www. clinicaltrials. gov; Unique identifier: NCT03500302). 3 Here, we investigated 15 of the 19 people with HIV in this study for whom we had stored serum samples and measured Lp (a) and LDL-C to examine the association of the changes in Lp (a) and LDL-C with the changes in CEF.The data and methods used in the analysis, and materials used to conduct the research that support the findings of this study are available from the corresponding author upon reasonable request. The study was approved by the Johns Hopkins Medicine Institutional Review Board and all participants provided informed written consent. Magnetic resonance imaging scans for CEF were performed before and 6 weeks following the initiation of evolocumab, 420 mg subcutaneously, every 4 weeks. All participants were on antiretroviral therapy and had a plasma HIV RNA of≤ 27 copies/mL. Statistical analysis was performed using GraphPad Prism 9.5. 0 and SAS 9.4. Categorical variables were compared using the Fisher exact test. Data were tested for normality using the Shapiro-Wilk test. Parametric and nonparametric tests were used for normally distributed and skewed data, respectively, to compare paired Lp (a), LDL-C, and CEF measures at baseline before PCSK9 inhibition, and at follow-up. Generalized estimation equation analysis was used to assess the longitudinal correlation between CEF and Lp (a) and between CEF and LDL-C.