We evaluated in a double-blind, placebo-controlled, randomized trial of 45 well-defined patients with
familial combined hyperlipidemia, the effect of
gemfibrozil (1,200 mg/day) or
simvastatin (20 mg/day) on
apolipoprotein-B (
apo-B)-containing
lipoproteins, low-density lipoprotein (
LDL) subfraction profile, and
LDL oxidizability. Although both drugs reduced plasma
cholesterol and
triglyceride concentrations,
gemfibrozil reduced plasma
triglycerides more effectively and
simvastatin reduced plasma
cholesterol more effectively.
LDL cholesterol was reduced with
simvastatin. With both drugs, total serum
apo-B concentration decreased. With
gemfibrozil, this was due to an exclusive reduction (-46%) of very low/
intermediate-density lipoprotein (VLDL + IDL)
apo-B, whereas
simvastatin decreased
apo-B in both VLDL + IDL and
LDL (34% and 15%, respectively). Initially, a dense
LDL subfraction profile was present in all patients. The decrease in
LDL cholesterol with
simvastatin was due to a decrease in all isolated
LDL subfractions except
LDL2;
gemfibrozil increased
LDL1 and
LDL2 cholesterol (p = 0.001) and reduced LDL4
cholesterol, resulting in a more buoyant
LDL subfraction profile compared with
simvastatin. In both groups, a predominance of small dense
LDL remained despite
therapy.
LDL fatty acid composition showed a shift from
oleic acid to
linoleic acid after
gemfibrozil;
arachidonic acid increased after
simvastatin.
Vitamin E was lower after
gemfibrozil. In the measurements of
LDL oxidation, only the oxidation rate was significantly reduced with
simvastatin. Thus, quantitative and qualitative changes of
LDL cholesterol had only a small effect on total in vitro
LDL oxidizability in this population with
familial combined hyperlipidemia.