Sahebkar Amirhossein
From the Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Cardiol Rev. 2014 Nov-Dec;22(6):306-12. doi: 10.1097/CRD.0000000000000025.
Proprotein convertase subtilisin kexin type 9 (PCSK9) affects lipid metabolism through modulation of low-density lipoprotein (LDL) receptor degradation. Circulating PCSK9 status is an important determinant of LDL-cholesterol levels and is thus implicated in atherogenesis. The present study aimed to resolve inconsistencies in clinical findings on the impact of fibrate therapy on circulating PCSK9 concentrations using a meta-analysis of all published studies. A comprehensive literature search in Medline and Scopus was carried out to identify clinical reports on the impact of treatment with fibrates on circulating concentrations of PCSK9. A meta-analysis of eligible studies was performed using a random-effects model. A weighed mean difference (WMD) with 95% confidence interval (CI) was used to assess the magnitude of fibrates' effect on PCSK9 concentrations. Six studies comprising 218 subjects fulfilled the eligibility criteria and were included for systematic review and quantitative data synthesis. A meta-analysis indicated a significant elevation of circulating PCSK9 concentrations following fibrate therapy (WMD: +60.37; 95% CI: 11.04-109.71; P = 0.02). The PCSK9-elevating effect of fibrates remained significant after comparison with a control group receiving either placebo or a statin (WMD: +23.97; 95% CI: 5.68-42.26; P = 0.01). Meta-regression analysis indicated that the effect size of fibrates in modulating circulating PCSK9 levels is not dependent on the duration of treatment (point estimate for slope = 0.59, SE = 4.56; 95% CI = -8.34 to 9.53; z = 0.130, P = 0.897). Fibrate therapy is associated with a significant increase in circulating PCSK9 concentrations. Such a PCSK9 elevation may partly explain the modest efficacy of fibrates on LDL-C.
前蛋白转化酶枯草溶菌素9型（PCSK9）通过调节低密度脂蛋白（LDL）受体降解来影响脂质代谢。循环中的PCSK9状态是LDL胆固醇水平的重要决定因素，因此与动脉粥样硬化的发生有关。本研究旨在通过对所有已发表研究进行荟萃分析，解决关于贝特类药物治疗对循环PCSK9浓度影响的临床研究结果不一致的问题。在Medline和Scopus中进行了全面的文献检索，以确定关于贝特类药物治疗对循环PCSK9浓度影响的临床报告。使用随机效应模型对符合条件的研究进行荟萃分析。采用加权平均差（WMD）及95%置信区间（CI）来评估贝特类药物对PCSK9浓度的影响程度。六项研究共218名受试者符合纳入标准，被纳入系统评价和定量数据合成。荟萃分析表明，贝特类药物治疗后循环PCSK9浓度显著升高（WMD：+60.37；95%CI：11.04 - 109.71；P = 0.02）。与接受安慰剂或他汀类药物的对照组相比，贝特类药物升高PCSK9的作用仍然显著（WMD：+23.97；95%CI：5.68 - 42.26；P = 0.01）。荟萃回归分析表明，贝特类药物调节循环PCSK9水平的效应大小不依赖于治疗持续时间（斜率的点估计值 = 0.59，标准误 = 4.56；95%CI = -8.34至9.53；z = 0.130，P = 0.897）。贝特类药物治疗与循环PCSK9浓度显著升高有关。这种PCSK9升高可能部分解释了贝特类药物对LDL-C的疗效有限。
