Journal of Lipid Research, Vol 37, 1298-1308, Copyright © 1996 by Lipid Research, Inc.
Effect of gemfibrozil on levels of lipoprotein[a] in type II hyperlipoproteinemic subjects
PH Jones, HJ Pownall, W Patsch, JA Herd, JA Farmer, C Payton-Ross, KT Kimball, AM Gotto and JD Morrisett
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Plasma lipoprotein[a] (Lp[a]) levels are highly correlated with
angiographically demonstrable coronary heart disease, and elevated Lp[a] is
an independent risk factor for atherosclerosis. Previous studies have
provided evidence that the levels of Lp[a] and triglyceride are related,
suggesting that Lp[a] might be altered by gemfibrozil, a drug well known
for its efficacy in reducing plasma triglycerides. Accordingly, 18 type IIa
and 16 type IIb hyperlipoproteinemic males aged 35-58 were treated for 3
months with 600 mg of gemfibrozil twice daily. The efficacy of the drug in
altering lipid and lipoprotein levels was different in the two type groups.
In type IIa and IIb subjects the respective changes in median levels were:
total cholesterol, -7.5 and -8.5% triglycerides, -35.6 and -54.4%; HDL-
cholesterol, +9.0 and +11.0%; and Lp[a], -17.2 and +6.1%. Before and after
gemfibrozil treatment, 7 type IIa and 10 type IIB subjects were given a 100
g/2 m2 oral-fat load; triglycerides and Lp[a] were measured post-prandially
at 0, 2, 4, 6, 8, and 10 h. The differences between before- and
after-gemfibrozil post-prandial curve integrated areas (PPCIA) were
compared for triglycerides and Lp[a]. The changes in median PPCIA for
triglycerides in types IIa and IIB were -54% and -53%, and for Lp[a] were
-8% and +8%, respectively. These results indicate i) that the levels of
Lp[a] are about 2 times higher in type IIa than IIb subjects, and ii) that
although gemfibrozil elicits a rather uniform decrease in fasting and
post-prandial triglyceride levels in type IIa and IIb patients, the drug
causes heterogeneous changes in Lp[a], suggesting that different metabolic
mechanisms may be dominant in subjects showing opposing effects.
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