Kg. Parhofer et al., EFFECT OF PRAVASTATIN ON METABOLIC PARAMETERS OF APOLIPOPROTEIN-B IN PATIENTS WITH MIXED HYPERLIPOPROTEINEMIA, The Clinical investigator, 71(11), 1993, pp. 939-946
3-Hydroxy-3-methylgluratyl coenzyme A reductase inhibitors reduce plas
ma cholesterol in different forms of hyperlipoproteinemia. Although an
increase in low-density lipoprotein (LDL) receptor activity is the pr
oven mechanism of this therapy in familial hypercholesterolemia, the m
echanism remains controversial in mixed hyperlipoproteinemia. A decrea
sed production of apolipoprotein B (apoB) and/or an increased removal
of lipoproteins could mediate the hypocholesterolemic effect of these
drugs. The effect of pravastatin on the metabolism of apoB was evaluat
ed in a randomized, double blind, placebo controlled, cross-over study
in five men with mixed hyperlipoproteinemia. Metabolic parameters for
apoB were determined using endogenous labeling with [1-C-13]leucine a
nd [N-15]glycine and multicompartmental modeling. During pravastatin t
herapy cholesterol, LDL cholesterol, apoB, and LDL apoB levels were si
gnificantly reduced (P<0.01) by 18%, 20%, 27%, and 29%, respectively,
while triglyceride and high-density lipoprotein cholesterol levels rem
ained unchanged. Pravastatin therapy increased the fractional cataboli
c rate of very low density lipoprotein apoB from 3.9 +/- 0.6 to 5.1 +/
- 1.7 per day (P=0.08) and that of LDL apoB from 0.37 +/- 0.09 to 0.46
+/- 0.10 per day (P<0.01). The apoB production (placebo 35.2 +/- 11.9
mg/kg per day; pravastatin 25.8 +/- 8.7 mg/kg per day) and conversion
of very low density lipoprotein apoB to LDL apoB (placebo 65%, pravas
tatin 57%) remained stable. Thus, also in mixed hyperlipoproteinemia 3
-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase the
catabolism of apoB-containing lipoproteins without significantly affe
cting the production of apoB.