Endothelin Receptor Antagonism Improves Lipid Profiles and Lowers PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) in Patients With Chronic Kidney Disease
Endothelin Receptor Antagonism Improves Lipid Profiles and Lowers PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) in Patients With Chronic Kidney Disease
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DOI：
10.1161/hypertensionaha.119.12919
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发表时间：
2019-08-01
期刊：
影响因子：
8.3
通讯作者：
Dhaun, Neeraj
中科院分区：
文献类型：
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作者：
Farrah, Tariq E.;Anand, Atul;Dhaun, Neeraj
血脂异常在慢性肾脏疾病（CKD）中很常见。尽管使用他汀类药物，许多患者仍不能充分降低血脂，心血管疾病的风险仍在增加。选择性ETA（内皮素- a）受体拮抗剂降低心血管疾病的危险因素。临床前数据表明，ETA拮抗剂对循环脂质有有益作用。我们评估了选择性ETA拮抗剂对CKD循环脂质和PCSK9（蛋白转化酶枯草杆菌素/kexin 9型）的影响。这是一项完全随机、双盲、3期交叉研究的二次分析。27名接受最佳心脏和肾脏保护治疗的透析前CKD患者被随机分配接受6周的安慰剂、选择性ETA受体拮抗剂、西他坦或长效硝苯地平。我们分别在基线、3周和6周后测量循环脂质和PCSK9。在每个研究阶段之前，基线脂质和PCSK9没有差异。而安慰剂和硝苯地平对血脂没有影响，6周的ETA拮抗剂显著降低总胆固醇（-11 +/- 1%）和低密度脂蛋白相关胆固醇（-20 +/- 3%），脂蛋白(a)（-16 +/- 2%）和甘油三酯（-20 +/- 4%）；高密度脂蛋白相关胆固醇升高（+14 +/- 2%）
Dyslipidemia is common in chronic kidney disease (CKD). Despite statins, many patients fail to adequately lower lipids and remain at increased risk of cardiovascular disease. Selective ETA (endothelin-A) receptor antagonists reduce cardiovascular disease risk factors. Preclinical data suggest that ETA antagonism has beneficial effects on circulating lipids. We assessed the effects of selective ETA antagonism on circulating lipids and PCSK9 (proprotein convertase subtilisin/kexin type 9) in CKD. This was a secondary analysis of a fully randomized, double-blind, 3-phase crossover study. Twenty-seven subjects with predialysis CKD on optimal cardio- and renoprotective treatment were randomly assigned to receive 6 weeks dosing with placebo, the selective ETA receptor antagonist, sitaxentan, or long-acting nifedipine. We measured circulating lipids and PCSK9 at baseline and then after 3 and 6 weeks. Baseline lipids and PCSK9 did not differ before each study phase. Whereas placebo and nifedipine had no effect on lipids, 6 weeks of ETA antagonism significantly reduced total (-11 +/- 1%) and low-density lipoprotein-associated (-20 +/- 3%) cholesterol, lipoprotein (a) (-16 +/- 2%) and triglycerides (-20 +/- 4%); high-density lipoprotein-associated cholesterol increased (+14 +/- 2%), P