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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.
Circulation. 2004 Sep 14; 110(11):1406-12.Circ

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/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.

Authors+Show Affiliations

Vascular Medicine Program, Department of Medicine, University of California San Diego, 9500 Gilman Dr, BSB 1080, La Jolla, CA 92093-0682, USA. stsimikas@ucsd.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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.

Language

eng

PubMed ID

15353498

Citation

Tsimikas, Sotirios, et al. "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." Circulation, vol. 110, no. 11, 2004, pp. 1406-12.
Tsimikas S, Witztum JL, Miller ER, et al. 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. Circulation. 2004;110(11):1406-12.
Tsimikas, S., Witztum, J. L., Miller, E. R., Sasiela, W. J., Szarek, M., Olsson, A. G., & Schwartz, G. G. (2004). 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. Circulation, 110(11), 1406-12.
Tsimikas S, et al. 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. Circulation. 2004 Sep 14;110(11):1406-12. PubMed PMID: 15353498.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Tsimikas,Sotirios, AU - Witztum,Joseph L, AU - Miller,Elizabeth R, AU - Sasiela,William J, AU - Szarek,Michael, AU - Olsson,Anders G, AU - Schwartz,Gregory G, AU - ,, Y1 - 2004/09/07/ PY - 2004/9/9/pubmed PY - 2005/4/12/medline PY - 2004/9/9/entrez SP - 1406 EP - 12 JF - Circulation JO - Circulation VL - 110 IS - 11 N2 - 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. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/15353498/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_ L2 - http://www.ahajournals.org/doi/full/10.1161/01.CIR.0000141728.23033.B5?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -