Effects of atorvastatin on inflammation and oxidative stress

Treatment with inhibitors of 3-hydroxyl-3-methylglutaryl coenzyme A reductase (statins) reduces the incidence of cardiovascular events, but it is unclear whether the beneficial effects are mediated solely by their lipid-lowering properties. We therefore investigated whether atorvastatin reduces inflammation and oxidative stress independently of its lipid-lowering effects. The subjects comprised 71 hyperlipidemic patients (64+/-9 years old, mean+/-SD) who were not receiving medical treatment. Serum lipid and C-reactive protein (CRP) levels, and urine 8-isoprostane level (an index of oxidative stress) were measured before and after 4 weeks of treatment with atorvastatin at 10 mg/day. In 38 patients, these biochemical variables and carotid intima-media thickness (IMT) were also measured after 6 months of treatment with atorvastatin. Atorvastatin markedly reduced CRP (from 0.69+/-0.36 to 0.42+/-0.20 and 0.35+/-0.19 mg/l, median+/-median absolute deviation, P<0.0001), 8-isoprostane (from 225+/-99 to 178+/-75 and 179+/-60 ng/g creatinine, P<0.05), and low density-lipoprotein cholesterol (LDLC; from 165+/-21 to 106+/-18 and 112+/-17 mg/dl, P<0.0001) after 4 weeks and 6 months of treatment, respectively. However, the reductions in CRP and 8-isoprostane were not correlated with those of LDLC. After 6 months of treatment, IMT was significantly decreased compared with the baseline value (from 0.94+/-0.26 to 0.90+/-0.20 mm, P<0.05), but this was not correlated with the reduction in LDLC. These results suggest that atorvastatin has beneficial effects on inflammation, oxidative stress, and the lipid profile in patients with hyperlipidemia. The extra-lipid effects are not attributable to the lipid-lowering effect of the statin, suggesting that the pleiotropic effects of atorvastatin are independent of its effects on the lipid profile.