Simvastatin-induced changes in circulating oxidized low-density lipoprotein in different types of dyslipidemia

Beyond lowering lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors (statins) have been shown to possess antioxidant properties, which may explain some of their beneficial effects in reducing atherosclerosis. We sought to determine whether circulating oxidized low-density lipoprotein (ox-LDL) levels differ between subjects with isolated hypercholesterolemia and combined hyperlipidemia, as well as the effect of simvastatin on circulating ox-LDL according to the type of dyslipidemia. Twenty-five subjects with total cholesterol >200 mg/dl and triglycerides <150 mg/dl, and 22 subjects with total cholesterol >200 mg/dl and triglycerides >150 mg/dl were treated with 40 mg simvastatin daily for 3 months. Serum lipids, C-reactive protein, fibrinogen, ox-LDL, and free radicals were measured at baseline and after 3 months of treatment. In both groups studied, simvastatin significantly improved lipids, and reduced C-reactive protein and fibrinogen levels. Free radicals were significantly reduced only in subjects with hypercholesterolemia. Subjects with combined hyperlipidemia had significantly higher baseline levels of ox-LDL compared to those with hypercholesterolemia (64.6 U/l vs 53.5 U/l, P = 0.03). Ox-LDL levels were reduced by 12% in subjects with hypercholesterolemia (P = 0.03) and by 26% in subjects with combined hyperlipidemia (P = 0.001) after simvastatin treatment. In conclusion, subjects with combined hyperlipidemia have increased levels of circulating ox-LDL compared to subjects with isolated hypercholesterolemia. Simvastatin significantly reduced circulating ox-LDL in both groups, but whether this reduction is related to clinical outcomes remains to be shown.