Introduction Directory UMM :Data Elmu:jurnal:A:Atherosclerosis:Vol153.Issue1.Nov2000:
Atherosclerosis 153 2000 129 – 138
The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and
oxidizability in patients with hypertrygliceridemia
Anton F.H. Stalenhoef
a,
, Jacqueline de Graaf
a
, Marianne E. Wittekoek
b
, Sebastian J.H. Bredie
a
, Pierre N.M. Demacker
a
, John J.P. Kastelein
b
a
541
Department of Internal Medicine, Uni6ersity Hospital Nijmegen, PO Box
9101
,
6500
HB Nijmegen, The Netherlands
b
Centre for Vascular Medicine, Academic Medical Centre, Uni6ersity of Amsterdam, Amsterdam, The Netherlands Received 23 April 1999; received in revised form 6 December 1999; accepted 7 January 2000
Abstract
We evaluated in a double-blind randomized trial with a double-dummy design in 28 patients with primary hypertriglyceridemia, the effect of gemfibrozil 1200 mgday versus Omacor 4 gday, a drug containing the n-3 fatty acids eicosapentaenoic EPA and
docosahexaenoic acid DHA, on lipid and lipoprotein levels, low density lipoprotein LDL subfraction profile and LDL oxidizability. Both Omacor and gemfibrozil therapy resulted in a similar significant decrease in serum triglyceride TG, very low
density lipoprotein VLDL triglyceride and VLDL cholesterol concentrations and an increase in high density lipoprotein HDL and LDL cholesterol concentrations. The increase in LDL cholesterol was due to a significant increase in cholesterol content of
the relatively buoyant LDL subfractions LDL1, LDL2 and LDL3, whereas the relative contribution of the dense LDL subfractions LDL4 and LDL5 to total LDL tended to decrease. So, both therapies resulted in a more buoyant LDL subfraction
profile, reflected by a significant increase of the value of parameter K + 10.3 on Omacor vs + 26.5 on gemfibrozil therapy, gemfibrozil vs Omacor P \ 0.05. Cu
2 +
-induced oxidation of LDL was measured by continuous monitoring of conjugated dienes. After 12 weeks of Omacor treatment LDL appeared more prone to oxidative modification in vitro than LDL after gemfibrozil
treatment, as measured by the significantly decreased lag time, preceding the onset of the lipid peroxidation. In both groups the rate of oxidation did not change with therapy. The amount of dienes formed during oxidation increased significantly on Omacor
treatment, but not on gemfibrozil treatment. Plasma thiobarbituric acid reactive substances were higher after Omacor and lower after gemfibrozil treatment, although not significantly. We conclude that both Omacor and gemfibrozil have favorable effects on
lipid and lipoprotein concentrations and the LDL subfraction profile. However, Omacor increased the susceptibility of LDL to oxidation, whereas gemfibrozil did not affect the resistance of LDL to oxidative modification in vitro. The clinical relevance of
these changes remains to be established in the light of other postulated favorable effects of n-3 fatty acids on the course of cardiovascular disease. © 2000 Elsevier Science Ireland Ltd. All rights reserved.
Keywords
:
Fish oil; Gemfibrozil; Omega-3 fatty acids; Hypertriglyceridemia; Low density lipoprotein subfractions; Low density lipoprotein oxidation
www.elsevier.comlocateatherosclerosis