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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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Original languageEnglish
Pages (from-to)323-330
Number of pages8
JournalHypertension
Volume74
Issue number2
Early online date10 Jun 2019
DOIs
Publication statusPublished - Aug 2019

Abstract

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

    Research areas

  • atherosclerosis, cardiovascular disease, cholesterol, endothelins, triglycerides, CARDIOVASCULAR RISK, INSULIN SENSITIVITY, LDL CHOLESTEROL, REDUCING LIPIDS, EFFICACY, SAFETY, ASSOCIATION, ATRASENTAN, EVOLOCUMAB, REDUCTION

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