Rates of Lipoprotein(a) Oxidation Accelerate at Elevated Levels and Attenuate With Atorvastatin Active Metabolites Compared With Other Statins.

Lipoprotein(a) [Lp(a)] levels are associated with increased cardiovascular risk, possibly linked to its oxidized phospholipid content that may accelerate lipoprotein oxidation. Attenuating this process could reduce Lp(a) atherogenicity. Atorvastatin is metabolized into 2 hydroxylated metabolites, which account for low-density lipoprotein reduction and potential antioxidant activity. We compared these metabolites' effects to other active statins on oxidation of plasma samples enriched with various levels of Lp(a) or other apolipoprotein B particles, as well as lipid membranes enriched with cholesterol. Lp(a) oxidized more rapidly than other apolipoprotein B particles and accelerated in a nonlinear fashion at levels associated with cardiovascular risk. The metabolites inhibited oxidation of each fraction in contrast to other statins and consistent with cholesterol-enriched membranes. The metabolites' unique phenoxy group facilitated membrane partitioning, leading to free radical scavenging activity as compared with other statins. The antioxidant actions of atorvastatin metabolites may reduce the atherogenicity of Lp(a) in patients independent of their levels.