期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 35, 期 1, 页码 164-172出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00005344-200001000-00022
关键词
fenofibrate; micronized; hypertriglyceridemia; HDL; postprandial
A randomized, double-blind, placebo-controlled study was undertaken in 20 hypertriglyceridemic men [plasma triglyceride (TG), >2.3 mM] with low levels (<0.9 mM) of high-density lipoprotein cholesterol (HDL-C) to investigate the ability of micronized fenofibrate (Tricor or Lipidil; 200 mg/ day) to affect atherogenic and thrombogenic plasma risk factors in the fed and fasted state. Each patient underwent (a) 4 weeks of dietary stabilization, (b) 8 weeks of treatment with fenofibrate or placebo, (c) a 5-week washout period, and (d) 8-weeks of treatment with the alternative medication. An oral fat-loading test (1 g fat/kg body weight) was carried out after both treatment periods. Before treatment, patients had a mean (+/-SD) total plasma TG of 3.31 +/- 0.93 mM; total C, 5.75 +/- 0.89 mM; HDL-C, 0.71 +/- 0.09 mM; and low-density lipoprotein (LDL)C, 3.40 +/- 0.68 mM. Compared with placebo, fenofibrate reduced fasting TG levels by 36%, and triglyceride-rich lipoprotein (TRL, d < 1.006 g/ml) -TG, and TRL-C levels by similar to 40%. In the postprandial state, fenofibrate reduced total TG, TRL-TG, TRL-C, TRL-apoC-III, and TRL-apoE levels by similar to 35% (all values of p < 0.01). Fasted and fed HDL-C and apoA-I levels were increased similar to 10%, and total cholesterol/HDL cholesterol ratios were decreased similar to 15% by fenofibrate. No significant differences were observed in mean LDL-C and LDL-apoB levels. A 6% increase in the LDL-C/LDL-apoB ratio during fenofibrate treatment indicated a shift to larger, more buoyant LDL par tides. A small, but statistically significant (p < 0.01) increase was observed in fasted and fed Lp(a) levels during fenofibrate treatment. Hemostatic parameters were not significantly affected by fenofibrate, except for a 12-15% decrease (p < 0.05) in fibrinogen levels in the fasted and fed state, and a significant increase (43%; p < 0.05) in fasting levels of plasminogen activator-inhibitor-1. These data demonstrate that micronized fenofibrate is highly effective, in both the fed and fasted state, in reducing TRL lipids and apolipoproteins, and in reducing plasma fibrinogen levels of men with an atherogenic lipoprotein profile.
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