Objectives: This study was designed to test the hypothesis that circulating biomarkers of oxidized low-density lipoprotein (OxLDL) are affected by statin therapy and predict changes in atheroma volume. Background: Oxidative stress is thought to play an important role in atherogenesis but the relationship between OxLDL, statin therapy, and atheroma volume in humans is not known. Methods: In a subgroup of 214 patients from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) trial, oxidized phospholipids (OxPL) and malondialdehyde (MDA) epitopes per apolipoprotein B-100 (apoB), immunoglobin (Ig) G and IgM apoB immune complexes, and OxLDL autoantibodies were measured at baseline and after 18 months of treatment with atorvastatin or pravastatin. Relationships between changes of OxLDL biomarkers and quantitative coronary angiography (QCA), total atheroma volume, and percentage atheroma volume were analyzed. Results: There were no differences in QCA parameters or atheroma volume in the 2 groups at baseline. Compared with baseline values, OxPL/apoB and MDA/apoB, and lipoprotein (a) levels increased 21% to 48% (p < 0.001 for all) in response to atorvastatin and 17% to 39% (p < 0.001 for all) in response to pravastatin. In contrast, IgG apoB immune complexes, IgM apoB immune complexes, and IgM OxLDL autoantibodies were significantly reduced by both atorvastatin and pravastatin (p value range 0.003 to <0.001). There were no significant differences between the atorvastatin and pravastatin groups. In the entire cohort, there were no correlations between changes in any OxLDL biomarkers and changes in QCA parameters or atheroma volume. Conclusions: Statin therapy results in significant increases in OxPL/apoB, MDA/apoB, and lipoprotein (a) levels and decreases in apoB immune complexes and OxLDL autoantibodies. However, these measures did not correlate with changes in QCA parameters or atheroma volume.
Bibliographical noteFunding Information:
Drs. Tsimikas and Witztum are named as inventors of patents related to antibodies to oxidized low-density lipoprotein owned by the University of California. Supported by an investigator-initiated grant from Pfizer Inc and from the Fondation Leducq. Assistance in developing the figures, but not content development support, was provided by Envision Pharma and was funded by Pfizer Inc. Drs. Messig and Ntanios are employees of Pfizer Inc. Peter Libby, MD, served as Guest Editor for this article.
- lipoprotein (a)
- oxidized phospholipids