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(Circulation. 2004;110:1406-1412.)
© 2004 American Heart Association, Inc.

Original Articles

High-Dose Atorvastatin Reduces Total Plasma Levels of Oxidized Phospholipids and Immune Complexes Present on Apolipoprotein B-100 in Patients With Acute Coronary Syndromes in the MIRACL Trial

Sotirios Tsimikas, MD; Joseph L. Witztum, MD; Elizabeth R. Miller, BS; William J. Sasiela, PhD; Michael Szarek, SM; Anders G. Olsson, MD PhD; Gregory G. Schwartz, MD PhD, for the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators

From the Department of Medicine, University of California San Diego (S.T., J.L.W., E.R.M.); the Cardiology Division, Veterans Affairs Medical Center and University of Colorado Health Sciences Center, Denver (G.G.S.); the Department of Medicine and Care, Faculty of Health Sciences, University of Linköping, Linköping, Sweden (A.G.O.); and Pfizer Pharmaceuticals Group, New York, NY (W.J.S., M.S.).

Correspondence to Sotirios Tsimikas, MD, Vascular Medicine Program, University of California San Diego, 9500 Gilman Dr, BSB 1080, La Jolla, CA 92093-0682. E-mail stsimikas{at}ucsd.edu

Received April 18, 2004; revision received July 5, 2004; accepted July 8, 2004.

Background— Oxidized phospholipids (OxPL) are present within atherosclerotic plaques and bound by lipoprotein (a) [Lp(a)] in plasma. This study evaluated the impact of atorvastatin on oxidized LDL (OxLDL) in patients with acute coronary syndromes (ACS).

Methods and Results— OxLDL-E06 (OxPL content on apolipoprotein B-100 [apoB] detected by antibody E06), apoB-100 immune complexes (apoB-IC), OxLDL autoantibodies, and Lp(a) levels were measured in 2341 patients at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. The OxLDL-E06 and apoB-IC data are reported per apoB-100 particle (OxPL/apoB, IC/apoB) and as total levels on all apoB-100 particles (total apoB-OxPL and total apoB-IC [eg, OxPL/apoB or IC/apoBxapoB-100 levels]). Compared with baseline values, atorvastatin reduced apoB-100 (–33%), total apoB-OxPL (–29.7%), total apoB-IC IgG (–29.5%), and IgM (–25.7%) (P<0.0001 for all), whereas no change or an increase was observed with placebo. When normalized per apoB-100, compared with placebo, atorvastatin increased OxPL/apoB (9.5% versus –3.9%, P<0.0001) and Lp(a) (8.8% versus –0.7%, (P<0.0001). A strong correlation was noted between OxPL/apoB and Lp(a) (R=0.85, P<0.0001), consistent with previous data that Lp(a) binds OxPL.

Conclusions— After atorvastatin treatment, total OxPL on all apoB-100 particles was decreased. However, there was enrichment of OxPL on a smaller pool of apoB-100 particles, in parallel with similar increases in Lp(a), suggesting binding by Lp(a). These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL, which may contribute to a reduction in ischemic events after ACS.

Key Words: atherosclerosis • antibodies • lipoproteins • oxidation

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