Knopp R H, Walden C E, Warnick G R, Albers J J, Ginsberg J, McGinnis B M
Department of Medicine, School of Medicine, University of Washington, Seattle.
Am J Med. 1987 Nov 27;83(5B):75-84. doi: 10.1016/0002-9343(87)90875-8.
In this segment of a multicenter study, 36 hypercholesterolemic patients were randomly assigned to fenofibrate or placebo treatment to assess effects on plasma concentrations of lipoprotein cholesterol and triglyceride, high-density lipoprotein-cholesterol subfractions, and apolipoproteins E, B, Al, and All. All of these factors are of known or potential value in determining the patient's risk of arteriosclerosis. Observations were made during initial screening and placebo phases, a 24-week, double-blind treatment phase, and a subsequent 24-week, open-label fenofibrate phase. There were three possible expressions of fenofibrate efficacy. Changes in lipoprotein cholesterol and total triglyceride concentrations observed in these patients were very similar to those seen with the larger multicenter cohort: total triglyceride levels decreased 38 to 46 percent, low-density lipoprotein cholesterol levels decreased 13 to 20 percent, and high-density lipoprotein cholesterol levels increased 4 to 13 percent. Triglyceride concentrations were significantly reduced (p less than 0.01) in very low-density lipoprotein (50 to 56 percent, similar to those of total triglyceride and very low-density lipoprotein cholesterol), and in low-density lipoprotein cholesterol levels (17 to 21 percent). A slight but statistically insignificant decrease in high-density lipoprotein triglyceride was observed (9 to 15 percent). High-density lipoprotein2 cholesterol levels did not change significantly, whereas high-density lipoprotein3 cholesterol levels increased 8 to 16 percent, accounting for all of the increase in high-density lipoprotein cholesterol. Apoprotein All levels increased significantly (13 to 20 percent) whereas those of apolipoprotein Al did not, consistent with an increase in high-density lipoprotein3 levels, where apolipoprotein All is more abundant relative to apolipoprotein Al than in high-density lipoprotein2. Apolipoprotein B levels decreased 20 to 26 percent and those of apolipoprotein E went from 29 to 34 percent, relative to the 16 to 20 percent decreases in very low-density lipoprotein and low-density lipoprotein triglyceride and cholesterol levels. Five patients with combined elevations of triglyceride and low-density lipoprotein cholesterol treated with fenofibrate, had reductions primarily in triglyceride, total apolipoprotein E (50 percent reduction), and apolipoprotein B (18 percent) levels. High-density lipoprotein3 cholesterol levels increased 19 percent and high-density lipoprotein2 cholesterol levels were unchanged. Low-density lipoprotein cholesterol levels declined slightly in four patients and a slight rise was observed in a fifth patient.(ABSTRACT TRUNCATED AT 400 WORDS)
在这项多中心研究的这一阶段,36名高胆固醇血症患者被随机分配接受非诺贝特或安慰剂治疗,以评估对脂蛋白胆固醇、甘油三酯、高密度脂蛋白胆固醇亚组分以及载脂蛋白E、B、A1和AII血浆浓度的影响。所有这些因素在确定患者的动脉硬化风险方面都具有已知或潜在价值。在初始筛查和安慰剂阶段、为期24周的双盲治疗阶段以及随后为期24周的非诺贝特开放标签阶段进行了观察。非诺贝特疗效有三种可能的表现形式。这些患者中观察到的脂蛋白胆固醇和总甘油三酯浓度变化与更大的多中心队列中观察到的变化非常相似:总甘油三酯水平下降38%至46%,低密度脂蛋白胆固醇水平下降13%至20%,高密度脂蛋白胆固醇水平上升4%至13%。极低密度脂蛋白中的甘油三酯浓度显著降低(p小于0.01)(50%至56%,与总甘油三酯和极低密度脂蛋白胆固醇的降低相似),低密度脂蛋白胆固醇水平也显著降低(17%至21%)。观察到高密度脂蛋白甘油三酯有轻微但无统计学意义的下降(9%至15%)。高密度脂蛋白-2胆固醇水平没有显著变化,而高密度脂蛋白-3胆固醇水平上升8%至16%,这解释了高密度脂蛋白胆固醇的全部上升。载脂蛋白AII水平显著上升(13%至20%),而载脂蛋白A1水平没有变化,这与高密度脂蛋白-3水平的上升一致,在高密度脂蛋白-3中,载脂蛋白AII相对于载脂蛋白A1比在高密度脂蛋白-2中更丰富。载脂蛋白B水平下降20%至26%,载脂蛋白E水平从29%降至34%,相对于极低密度脂蛋白和低密度脂蛋白甘油三酯及胆固醇水平16%至20%的下降。五名甘油三酯和低密度脂蛋白胆固醇合并升高的患者接受非诺贝特治疗后,主要是甘油三酯、总载脂蛋白E(降低50%)和载脂蛋白B(降低18%)水平下降。高密度脂蛋白-3胆固醇水平上升19%,高密度脂蛋白-2胆固醇水平未变。四名患者的低密度脂蛋白胆固醇水平略有下降,第五名患者略有上升。(摘要截断于400字)