Document Detail

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.
MedLine Citation:
PMID:  15353498     Owner:  NLM     Status:  MEDLINE    
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.
Sotirios Tsimikas; Joseph L Witztum; Elizabeth R Miller; William J Sasiela; Michael Szarek; Anders G Olsson; Gregory G Schwartz;
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Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-09-07
Journal Detail:
Title:  Circulation     Volume:  110     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-14     Completed Date:  2005-04-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1406-12     Citation Subset:  AIM; IM    
Vascular Medicine Program, Department of Medicine, University of California San Diego, 9500 Gilman Dr, BSB 1080, La Jolla, CA 92093-0682, USA.
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MeSH Terms
Angina, Unstable / blood,  drug therapy*,  immunology
Antigen-Antibody Complex / blood*
Apolipoprotein B-100
Apolipoproteins B / blood*
Autoantibodies / immunology
Double-Blind Method
Heptanoic Acids / administration & dosage,  therapeutic use*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage,  therapeutic use*
Immunoglobulin G / blood
Immunoglobulin M / blood
Lipoprotein(a) / blood
Lipoproteins, LDL / blood*,  immunology
Middle Aged
Myocardial Infarction / blood,  drug therapy*,  immunology
Phospholipids / blood*,  chemistry
Pyrroles / administration & dosage,  therapeutic use*
Grant Support
Reg. No./Substance:
0/Antigen-Antibody Complex; 0/Apolipoprotein B-100; 0/Apolipoproteins B; 0/Autoantibodies; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Immunoglobulin G; 0/Immunoglobulin M; 0/Lipoprotein(a); 0/Lipoproteins, LDL; 0/Phospholipids; 0/Pyrroles; 0/oxidized low density lipoprotein; 110862-48-1/atorvastatin
Comment In:
Circulation. 2005 May 10;111(18):e284-5; author reply e284-5   [PMID:  15883220 ]

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