Effects of treatment of hypertriglyceridaemia with gemfibrozil on serum lipoproteins and the transfer of cholesteryl ester from high density lipoproteins to low density lipoproteins.
Lipoprotein composition and cholesterol esterification, before and after treatment with gemfibrozil, have been examined in the fasting and postprandial state in nine patients with primary hypertriglyceridaemia who participated in a double-blind, placebo controlled study. After 8 weeks of treatment fasting serum triglycerides were reduced significantly from 6.05 mmol/l (range 2.48-10.99 mmol/l) to 1.76 mmol/l (range 1.16-11.90 mmol/l) (P less than 0.001). This was mainly due to a decrease in the triglyceride content of the Sf 12-20, 60-400 and Sf greater than 400 lipoprotein fractions (P less than 0.05). The Sf 0-12 fraction showed an increase in cholesteryl ester, free cholesterol, phospholipids and protein. Consistent with these findings there was a net increase in the mass concentration of the Sf 0-12 fraction (P less than 0.05) and a decrease in that of small very low density lipoproteins (Sf 20-60) (P less than 0.05). In the 8 patients in whom it was measured there was a 40% reduction in the rate at which cholesteryl esters derived from radiolabelled-free cholesterol appeared in very low density lipoprotein (VLDL) and low density lipoprotein (LDL) measured in an in vitro system (P less than 0.02), but serum lecithin:cholesterol acyl transferase (LCAT) activity was unchanged. At the end of each treatment phase (placebo or gemfibrozil) patients were given a mixed meal containing 100 g of fat. Treatment with gemfibrozil resulted in a reduction in serum triglyceride concentrations at all time points for at least 5 h after the meal (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Bhatnagar
D
D
University Department of Medicine, Manchester Royal Infirmary, U.K.
Durrington
P N
PN
Mackness
M I
MI
Arrol
S
S
Winocour
P H
PH
Prais
H
H
D000328:Adult; D002788:Cholesterol Esters / Q000097:blood*; D004311:Double-Blind Method; D015248:Gemfibrozil / Q000627:therapeutic use*; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000097:blood / Q000188:drug therapy*; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged
D002788:Cholesterol Esters; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D015248:Gemfibrozil