Cited by 225Lipoproteins and Cardiovascular HealthAtherosclerosis and Cardiovascular DiseasesCholesterol and Lipid Metabolism

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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

Tsimikas, Sotirios, Witztum, Joseph L., Miller, Elizabeth R., Sasiela, William J., Szarek, Michael, Olsson, Anders G., Schwartz, Gregory G.·2004·Circulation

DOI 10.1161/01.cir.0000141728.23033.b5

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Abstract

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/apoB×apoB-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.

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Authors: Tsimikas, S., Witztum, J. L., Miller, E. R., Sasiela, W. J., Szarek, M., Olsson, A. G., & Schwartz, G. G.
Affiliations: Linköping University (SE)
Corresponding author: Tsimikas, Sotirios
ORCID: Tsimikas, Sotirios
Witztum, Joseph L.
Miller, Elizabeth R.
Sasiela, William J.
Szarek, Michael
Olsson, Anders G.
Schwartz, Gregory G.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2004-09-14
Volume: 110
Issue: 11
Pages: 1406-1412
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.0000141728.23033.b5
OpenAlex: W2109629533
Semantic Scholar: 5d8d1d7bcae3432d2e03d42643169af12f5e5419
Cited by: 225
References: 45
Citations by year: 2026: 2 · 2025: 6 · 2024: 8 · 2023: 10 · 2022: 10 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 6 · 2016: 15 · 2015: 13 · 2014: 10 · 2013: 10 · 2012: 9
FWCI: 14.84
Type: journal article
Language: en
Open access: closed
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Funders: Donald W. Reynolds Foundation
Pfizer
National Heart, Lung, and Blood Institute (P50HL056989, HL-56989)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Keywords: atorvastatin, oxidized phospholipids, oxidized LDL, apolipoprotein B-100, immune complexes, lipoprotein(a), acute coronary syndrome, statin therapy, atherosclerosis, atherosclerotic plaque
MeSH terms: Atorvastatin, Aged, Angina, Unstable, Antigen-Antibody Complex, Apolipoproteins B, Autoantibodies, Double-Blind Method, Female, Heptanoic Acids, Humans, Immunoglobulin G, Immunoglobulin M, Lipoproteins, LDL, Male, Middle Aged, Myocardial Infarction, Oxidation-Reduction, Phospholipids, Pyrroles, Lipoprotein(a), Hydroxymethylglutaryl-CoA Reductase Inhibitors, Apolipoprotein B-100

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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

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