Abstract 475: Relationship Between Oxidized Phospholipid Content On Apolipoprotein B-100 Particles, Statin Therapy and Atheroma Volume: Observations From The REVERSAL Study
Background: Increased levels of oxidized phospholipids on apolipoprotein B-100 particles (OxPL/apoB) are associated with angiographically defined coronary artery disease, progression of carotid atherosclerosis and predict new cardiovascular events. Interestingly, OxPL/apoB levels increase in response to low-fat diets or therapy with different statins. Furthermore, during dietary-induced atherosclerosis regression in animals, increases in plasma OxPL/apoB levels are associated with reduced OxPL content in atheromatous plaques, suggesting a flux of OxPL from the vessel wall to the lumen.
Methods: In a subgroup of 220 patients from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, we measured several biomarkers of oxidized LDL (OxLDL), including OxPL/apoB and IgG and IgM apoB-100 immune complexes (apoB-IC) and OxLDL autoantibodies, at baseline and after 18 months of treatment with atorvastatin (AT) 80mg/d or pravastatin (PR) 40mg/d. Measures of total atheroma volume (TAV) and vessel remodeling with intravascular ultrasound (IVUS) were analyzed.
Results: Compared to baseline values, OxPL/apoB levels increased 58.5% (P<0.0001) in response to AT and 32.7% (P<0.0001) in response to PR. In contrast, IG apoB-IC, IgM apoB-IC and IgM OxLDL autoantibodies were significantly reduced by both AT and PR (p-value: range 0.04 – 0.0001). However, no differences in OxLDL biomarkers were noted between the AT and PR groups. In the entire group, there were no correlations between TAV and vessel remodeling with any OxLDL biomarkers at baseline or 18 months.
Conclusion: Statin therapy results in significant increases in OxPL/apoB and decreases in immune complexes and OxLDL autoantibodies. However, these measures do not correlate with atheroma volume or vessel wall remodeling measured by IVUS. Whether statin-induced changes in plaque characteristics, such as the lipid core, correlate with plasma OxLDL biomarkers remains to be determined.