DECREASED INVITRO OXIDIZABILITY OF LOW-DENSITY-LIPOPROTEIN IN HYPERCHOLESTEROLEMIC PATIENTS TREATED WITH 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE INHIBITORS

We studied the effects of the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors simvastatin and pravastatin on the in vitro susc eptibility of low-density lipoprotein (LDL) to oxidation. Twenty-three hypercholesterolaemic patients (mean serum cholesterol 9.7 mmol l-1) were treated with increasing doses of either simvastatin or pravastati n for 18 weeks. No significant differences in effect on lipid levels b etween the two drugs were found. Treatment resulted in lowering of tot al cholesterol and LDL-cholesterol by maximally 30% and 34%, respectiv ely. Chemical composition analysis showed that LDL particles contained relatively more protein and less free cholesterol and cholesteryl-est er after treatment. The LDL cholesterol/protein ratio decreased from 1 .24 +/- 0.21 to 0.97 +/- 0.23 (n = 20). By continuous monitoring of in vitro oxidation it appeared that LDL was less susceptible to oxidatio n after drug treatment. Maximal rate of diene production was significa ntly decreased from 19.7 +/- 3.1 to 18.5 +/- 3.3 nmol min-1 mg-1 LDL; total diene production decreased significantly from 420.3 +/- 67.6 to 380.5 +/- 49.1 nmol mg-1 LDL; the lag time was unchanged throughout th e study. These studies show that HMG-CoA reductase inhibitors reduce t he oxidizability of LDL by altering its composition.