The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin.

BACKGROUND: Atherogenic risk in subjects with metabolic syndrome is partly mediated by increased oxidative stress and subsequent endothelial dysfunction. Clinical trials have demonstrated differences in outcomes between subjects receiving lipophilic statins (atorvastatin) compared with hydrophilic statins (pravastatin). However, whether these findings are attributable to differences in the doses administered or to nonlipid-lowering pleiotropic effects of statins on oxidative stress and vascular function remains unknown. We hypothesized that equipotent doses of these two statins will have divergent effects on markers of oxidative stress and endothelial function.

METHODS: Thirty-six subjects with hyperlipidemia and metabolic syndrome and/or diabetes were randomized in a double-blind manner to either pravastatin 80 mg or atorvastatin 10 mg daily. Oxidative stress (dROMs assay that measures lipid hydroperoxides, plasma thiobarbituric acid reactive substances [TBARS], and aminothiol levels) and brachial artery flow-mediated dilation (FMD) were measured at baseline and after 12 weeks of statin therapy.

RESULTS: Statin therapy reduced serum low-density lipoprotein cholesterol levels equally in both groups. Atorvastatin therapy was associated with a significant reduction in TBARS (P = .006) and dROMs levels (P = .02), which was not observed in subjects treated with pravastatin. Endothelial function improved with statin therapy (P = .02), but there was no difference between the statin groups.

CONCLUSION: In hyperlipidemic subjects with metabolic syndrome, atorvastatin is associated with a greater reduction in lipid markers of oxidation compared with pravastatin. Whether these effects are responsible for the outcome differences in trials comparing these agents needs further investigation.