Effects of fenofibrate on high-density lipoprotein particle size in patients with hyperlipidemia: a randomized, double-blind, placebo-controlled, multicenter, crossover study.
BACKGROUND
Fenofibrate lowers serum total cholesterol and triglyceride levels while it elevates serum high-density lipoprotein cholesterol (HDL-C) level.


OBJECTIVE
The aim of this study was to investigate the effects of fenofibrate on the particle size of high-density lipoprotein (HDL).


METHODS
Patients with hyperlipidemia (as defined by serum triglyceride level > or = 150 mg/dL in the fasting state) were enrolled in this randomized, double-blind, placebo-controlled, multicenter, crossover study. Fenofibrate 300 mg (corresponding to 200 mg of micronized fenofibrate) or placebo was administered orally once daily after dinner for 8 weeks, followed by crossover of the 2 drugs for an additional 8 weeks.


RESULTS
Fifty hyperlipidemic patients (31 men, 19 women; mean [SD] age, 54.6 [12.7] years) were enrolled. Serum total cholesterol and triglyceride levels were significantly reduced with fenofibrate treatment compared with placebo (9.4% [P = 0.007] and 34.4% [P < 0.001], respectively), whereas HDL-C levels were significantly elevated (by 25.8% [P < 0.001]). Lipoprotein lipase (LPL) activity, LPL protein level, and hepatic triglyceride lipase activity increased by 10.5%, 13.4%, and 11.4%, respectively, with fenofibrate compared with placebo. HDL was classified into 3 groups by particle size: HDL3 <88 A; HDL2a > or = 88 A but <98 A; and HDL2b > or = 98 A. The amount of HDL3 increased significantly with fenofibrate compared with placebo (P < 0.001). Fenofibrate was well tolerated during the study. Abnormal clinical laboratory values were noted in 20 of 48 patients (41.7%), but these events were mild and not clinically significant.


CONCLUSIONS
Taken together, these findings indicate that fenofibrate therapy increased the HDL subfraction with the smallest diameter (HDL3), which is largely responsible for withdrawing cholesterol from peripheral cells.
Sasaki
Jun
J
Graduate School of Public Health Medicine, International University of Health and Welfare, Fukuoka, Japan. jsas@nifty.com
Yamamoto
Kyosuke
K
Ageta
Masato
M
D000328:Adult; D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008071:Lipoprotein Lipase / Q000097:blood; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D008071:Lipoprotein Lipase; D011345:Fenofibrate