Ohta Akio, Kato Hiroyuki, Ishii Satoshi, Nagai Yoshio, Tanaka Yasushi
Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
J Clin Med Res. 2017 Jun;9(6):476-481. doi: 10.14740/jocmr2782w. Epub 2017 Apr 26.
The aim of this study was to evaluate effect of ezetimibe monotherapy on serum low-density lipoprotein cholesterol (LDL-C) in Japanese patients and to investigate the association between changes of LDL-C and changes of markers for cholesterol synthesis and absorption.
Seventy-six hypercholesterolemic patients without statin therapy were enrolled and randomized to two groups, which were an ezetimibe group (group E, n = 44) and a control group without ezetimibe treatment that received diet therapy alone (group C, n = 32). The study period was 12 weeks. In group E, 10 mg of ezetimibe was administered daily after breakfast. Serum lipids were measured every 4 weeks, while lathosterol (a cholesterol synthesis marker) and campesterol and sitosterol (cholesterol absorption markers) were examined at baseline and at 12 weeks.
A significant reduction of LDL-C was observed in group E at both 4 and 12 weeks (from 155 ± 3.9 to 128 ± 3.4 mg/dL and 132 ± 3.9 mg/dL, respectively, both P < 0.01), associated with an increase of high-density lipoprotein cholesterol (HDL-C)at 12 weeks (from 53 ± 1.3 to 55 ± 1.5 mg/dL, P < 0.05) and no change of triglycerides. In contrast, none of these lipids changed in group C. An increase of lathosterol and a decrease of campesterol and sitosterol were observed in group E, while none of these markers changed in group C. When group E was divided into two subgroups according to the reduction of LDL-C, which were a good response group (reduction ≥ 20 mg/dL, ΔLDL-C = -27.9 ± 1.3 mg/dL, n = 18) and a poor response group (reduction < 20 mg/dL, ΔLDL-C = -3.7 ± 2.5 mg/dL, n = 26), baseline levels of campesterol and sitosterol were higher in the good response group.
Ezetimibe monotherapy reduced LDL-C and increased HDL-C, with the reduction of LDL-C being greater in patients with higher levels of cholesterol absorption markers.
本研究旨在评估依折麦布单药治疗对日本患者血清低密度脂蛋白胆固醇（LDL-C）的影响，并探讨LDL-C变化与胆固醇合成及吸收标志物变化之间的关联。
纳入76例未接受他汀类药物治疗的高胆固醇血症患者，随机分为两组，即依折麦布组（E组，n = 44）和仅接受饮食治疗的未使用依折麦布治疗的对照组（C组，n = 32）。研究期为12周。在E组中，早餐后每日服用10 mg依折麦布。每4周测量一次血脂，同时在基线和12周时检测羊毛甾醇（一种胆固醇合成标志物）以及菜油甾醇和谷甾醇（胆固醇吸收标志物）。
E组在4周和12周时LDL-C均显著降低（分别从155±3.9降至128±3.4 mg/dL和132±3.9 mg/dL，P均<0.01），同时12周时高密度脂蛋白胆固醇（HDL-C）升高（从53±1.3升至55±1.5 mg/dL，P<0.05），甘油三酯无变化。相比之下，C组这些血脂指标均无变化。E组观察到羊毛甾醇升高，菜油甾醇和谷甾醇降低，而C组这些标志物均无变化。当根据LDL-C降低情况将E组分为两个亚组时，即良好反应组（降低≥20 mg/dL，ΔLDL-C = -27.9±1.3 mg/dL，n = 18）和不良反应组（降低<20 mg/dL，ΔLDL-C = -3.7±2.5 mg/dL，n = 26），良好反应组的菜油甾醇和谷甾醇基线水平较高。
依折麦布单药治疗可降低LDL-C并升高HDL-C，胆固醇吸收标志物水平较高的患者LDL-C降低幅度更大。
