Goldberg A C, Schonfeld G, Anderson C, Dillingham M A
Lipid Research Center, Washington University, School of Medicine, St. Louis, Missouri 63110.
Am J Med. 1987 Nov 27;83(5B):60-5. doi: 10.1016/0002-9343(87)90872-2.
This study assessed the effects of fenofibrate on lipoprotein levels and lipoprotein compositions in a subgroup of patients who participated in a multicenter fenofibrate study. Eleven men and 10 women aged 29 to 63 were studied, 12 with type II A and nine with type II B hyperlipoproteinemia. Fasting blood samples were obtained every four to six weeks. Lipoprotein lipids were quantified by procedures of the Lipid Research Clinics, and apolipoproteins by radioimmunoassay. Fenofibrate decreased mean triglyceride and cholesterol levels of the type II A patients from 130 to 99 and from 286 to 237 mg/dl, respectively. Levels of very low-density lipoprotein triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol decreased and high-density lipoprotein cholesterol levels rose. Apolipoprotein B and apolipoprotein E levels decreased, whereas apolipoprotein AI and apolipoprotein AII levels rose. The mean very low-density lipoprotein cholesterol:very low-density lipoprotein triglyceride ratio and low-density lipoprotein cholesterol:low-density lipoprotein triglyceride ratio decreased. The low-density lipoprotein cholesterol:apolipoprotein B ratio and high-density lipoprotein cholesterol: apolipoprotein AII ratio decreased as did the apolipoprotein AI:apolipoprotein AII ratio. In patients with type II B hyperlipoproteinemia, triglyceride and cholesterol levels decreased with fenofibrate therapy with most of the decrease in triglyceride levels due to very low-density lipoprotein triglycerides, whereas the decrease in total cholesterol levels was due to decreases in very low-density lipoprotein and low-density lipoprotein cholesterol. High-density lipoprotein cholesterol levels rose. The decrease in low-density lipoprotein cholesterol levels was not significant in this group. Apolipoprotein E levels decreased and apoliprotein AI and apolipoprotein AII levels rose. Indices of composition in type II B patients were similar to those in type II A patients but the changes were less dramatic. Very low-density lipoprotein cholesterol:very low-density lipoprotein triglyceride ratios decreased significantly, but low-density lipoprotein cholesterol:low-density lipoprotein triglyceride ratios did not change significantly with treatment. The mean low-density lipoprotein cholesterol:apolipoprotein B ratio, high-density lipoprotein cholesterol:apolipoprotein AII ratio, and apolipoprotein AI:apolipoprotein AII ratio all were lowered by therapy. Thus, very low-density lipoprotein and low-density lipoprotein lost cholesterol in response to fenofibrate therapy and high-density lipoprotein particles became enriched in cholesterol.
本研究评估了非诺贝特对参与一项多中心非诺贝特研究的部分患者脂蛋白水平及脂蛋白组成的影响。研究对象为11名男性和10名女性,年龄在29至63岁之间,其中12例为IIA型高脂蛋白血症患者,9例为IIB型高脂蛋白血症患者。每四至六周采集一次空腹血样。脂蛋白脂质通过脂质研究临床中心的方法进行定量,载脂蛋白通过放射免疫测定法进行检测。非诺贝特使IIA型患者的平均甘油三酯和胆固醇水平分别从130降至99mg/dl以及从286降至237mg/dl。极低密度脂蛋白甘油三酯、低密度脂蛋白胆固醇和极低密度脂蛋白胆固醇水平降低,高密度脂蛋白胆固醇水平升高。载脂蛋白B和载脂蛋白E水平降低,而载脂蛋白AI和载脂蛋白AII水平升高。极低密度脂蛋白胆固醇与极低密度脂蛋白甘油三酯的平均比值以及低密度脂蛋白胆固醇与低密度脂蛋白甘油三酯的比值降低。低密度脂蛋白胆固醇与载脂蛋白B的比值、高密度脂蛋白胆固醇与载脂蛋白AII的比值以及载脂蛋白AI与载脂蛋白AII的比值均降低。在IIB型高脂蛋白血症患者中,非诺贝特治疗使甘油三酯和胆固醇水平降低,甘油三酯水平的降低主要归因于极低密度脂蛋白甘油三酯,而总胆固醇水平的降低则归因于极低密度脂蛋白和低密度脂蛋白胆固醇的减少。高密度脂蛋白胆固醇水平升高。该组中低密度脂蛋白胆固醇水平的降低不显著。载脂蛋白E水平降低,载脂蛋白AI和载脂蛋白AII水平升高。IIB型患者的组成指标与IIA型患者相似,但变化程度较小。极低密度脂蛋白胆固醇与极低密度脂蛋白甘油三酯的比值显著降低,但低密度脂蛋白胆固醇与低密度脂蛋白甘油三酯的比值在治疗后无显著变化。治疗使平均低密度脂蛋白胆固醇与载脂蛋白B的比值、高密度脂蛋白胆固醇与载脂蛋白AII的比值以及载脂蛋白AI与载脂蛋白AII的比值均降低。因此,极低密度脂蛋白和低密度脂蛋白在非诺贝特治疗后失去了胆固醇,而高密度脂蛋白颗粒中的胆固醇含量增加。