Effects of Evolocumab on Vitamin E and Steroid Hormone Levels Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study
Effects of Evolocumab on Vitamin E and Steroid Hormone Levels Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study
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DOI：
10.1161/circresaha.115.307071
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发表时间：
2015-09-25
影响因子：
20.1
通讯作者：
Roth, Eli
中科院分区：
文献类型：
--
作者：
Blom, Dirk J.;Djedjos, C. Stephen;Roth, Eli
理由：维生素 E 转运和类固醇生成与低密度脂蛋白 (LDL) 代谢密切相关，evolocumab 可以将 LDL 胆固醇 (LDL-C) 降低至低水平。目的：确定 evolocumab 对维生素 E 和类固醇激素水平的影响。方法和结果：根据心血管风险滴定背景降脂治疗后，901 名 LDL-C 2.0 mmol/L 的患者被随机分配到 52 周的治疗组。每月一次，皮下注射 evolocumab 或安慰剂。在基线和第 52 周对维生素 E、皮质醇、促肾上腺皮质激素和性腺激素进行分析。在一项子研究 (n=100) 中，还在基线和第 52 周测量了血清、LDL、高密度脂蛋白和红细胞膜中的维生素 E 水平。从基线到第 52 周，接受 evolocumab 治疗的患者的绝对维生素 E 降低了 16%，但胆固醇标准化后增加了 19%。在该亚研究中，维生素 E 水平从基线到第 52 周的变化反映了脂质部分的变化，而红细胞膜维生素 E 水平没有变化。到第 52 周，接受 evolocumab 治疗的患者的皮质醇从基线略有增加，但促肾上腺皮质激素和皮质醇：促肾上腺皮质激素的比率没有变化。没有患者有皮质醇：促肾上腺皮质激素比率
Rationale: Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels.Objective: To determine the effects of evolocumab on vitamin E and steroid hormone levels.Methods and Results: After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C 2.0 mmol/L were randomized to 52 weeks of monthly, subcutaneous evolocumab, or placebo. Vitamin E, cortisol, adrenocorticotropic hormone, and gonadal hormones were analyzed at baseline and week 52. In a substudy (n=100), vitamin E levels were also measured in serum, LDL, high-density lipoprotein, and red blood cell membranes at baseline and week 52. Absolute vitamin E decreased in evolocumab-treated patients from baseline to week 52 by 16% but increased by 19% when normalized for cholesterol. In the substudy, vitamin E level changes from baseline to week 52 mirrored the changes in the lipid fraction, and red blood cell membrane vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but adrenocorticotropic hormone and the cortisol:adrenocorticotropic hormone ratio did not change. No patient had a cortisol:adrenocorticotropic hormone ratio