Antioxidant effects of simvastatin in primary and secondary prevention of coronary heart disease

Abstract

The aim of the present study was to determine the effect of simvastatin on the levels of oxidized low-density lipoprotein (ox-LDL) and free radicals in hypercholesterolemic subjects undergoing primary and secondary prevention of coronary heart disease (CHD). Fifteen subjects with hypercholesterolemia and no obvious CHD and 29 subjects with hypercholesterolemia and stable angina received 40 mg of simvastatin daily for 12 weeks. Serum total cholesterol, HDL-cholesterol and triglyceride concentrations were determined by automated enzymatic assays whereas LDL-cholesterol was calculated using the Friedwald formula. The ox-LDL levels were determined by a commercially available ELISA kit. Free radicals were assessed by the Free Radical Analytical System (FRAS). Both in primary and secondary prevention, subjects had borderline levels of free radicals but in neither group there was a significant reduction of free radicals after simvastatin treatment. In subjects undergoing primary prevention of CHD, ox-LDL levels were reduced by 31.1+/-5.0% (P < 0.001) whereas in secondary prevention were reduced by 6.5+/-5.2% (P < 0.02) after simvastatin treatment. The reduction of ox-LDL levels did not correlate with the reduction of total cholesterol levels in either group studied. In both groups, ox-LDL levels were not associated with free radical levels either before or after simvastatin treatment. This study demonstrates that simvastatin can significantly reduce circulating ox-LDL levels both in subjects undergoing primary and secondary prevention of CHD. These results could partly explain the slowing down of the progression of atherosclerosis caused by HMG-CoA reductase inhibitors.