Simvastatin decreases aldehyde production derived from lipoprotein oxidation

Treatment with statins are known to lower plasma and low-density liporprote in (LDL) cholesterol levels with resultant prevention and regression of ath erosclerosis. It has been recently suggested that the action of the statins may also have a direct effect on other mechanisms involved;in the atherosc lerotic plague formation. Thus, we investigated whether simvastatin could h ave an antioxidant effect on plasma lipoproteins. The rate of oxidation of LDL and high-density lipoproteins (HDL) was measured by conjugated diene fo rmation with and without the addtion of increasing concentrations of simvas tatin tin vitro) and in patients with and without treatment with simvastati n (in vivo). A strong correlation was observed between increasing simvastat in concentration and the lag phase a negative correlation was observed fdr maximal rate and maximum diene production in LDL samples (r(2) = +0.97, p < 0.0001; r(2) = -0.92,p <0.0001; r(2) = -0.98, p <0.0001, respectively). For HDL no clear correlation could be established with the lag phase, but a st rong negative correlation was also observed between simvastatin concentrati on and maximal rate and maximum diene production (r(2) = -0.69, p <0.01; r( 2) = -0.98, p <0.00011 respectively). After b hours of oxidation the produc tion of aldehydes in LDL and HDL was lower (30% and 5%, respectively) in sa mples obtained during simvastatin therapy with respect to those obtained wi thout treatment. The 2,4-decadienal showed a decrease of 37% and 64% (p <0. 05) in both oxidized-LDL and oxidized-HDL particles, respectively, with sim vastatin treatment. Our findings demonstrate that simvastatin acts as an an tioxidant in lipoprotein particles and, together with its lipid-lowering pr operties, could play an important role in preventing atherosclerosis. (C) 1 999 by Excerpta Medica, Inc.