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 susceptibility 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 pravastatin for 18 weeks. No significant differences in effect on lipid levels between the two drugs were found. Treatment resulted in lowering of total cholesterol and LDL-cholesterol by maximally 30% and 34%, respectively. Chemical composition analysis showed that LDL particles contained relatively more protein and less free cholesterol and cholesteryl-ester 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 oxidation after drug treatment. Maximal rate of diene production was significantly 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 the study. These studies show that HMG-CoA reductase inhibitors reduce the oxidizability of LDL by altering its composition.