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J. Lipid Res.
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A more recent version of this article appeared on February 1, 2007

Papers In Press, published online ahead of print November 8, 2006
J. Lipid Res., doi:10.1194/jlr.M600361-JLR200
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Submitted on August 14, 2006
Revised on November 1, 2006
Accepted on November 7, 2006

Relationship of IgM and IgG autoantibodies to oxidized low density lipoprotein and apolipoprotein B100-immune complexes with angiographically determined coronary artery disease and cardiovascular events

Sotirios Tsimikas, Emmanouil S. Brilakis, Ryan J. Lennon, Elizabeth R. Miller, Joseph L. Witztum, Joseph P. McConnell, Kenneth S. Kornman, and Peter B. Berger

Medicine/Cardiology, University of California San Diego, La Jolla, CA 92093-0682

Corresponding Author: stsimikas{at}ucsd.edu

The relationship between autoantibodies (AB) to oxidized low density lipoprotein (OxLDL) and coronary artery disease (CAD) remains controversial. IgM and IgG OxLDL AB to malondialdehyde (MDA) modified-LDL, copper oxidized LDL (Cu-OxLDL) and to oxidized cholesterol linoleate (OxCL), as well as apolipoprotein B-100 immune complexes (ApoB-IC) were measured in 504 patients undergoing clinically-indicated coronary angiography. Patients were followed for cardiovascular events for a median of 4 years. In univariate analysis, IgM OxLDL autoantibodies and IgM ApoB-IC were inversely associated with the presence of angiographically-determined CAD whereas IgG OxLDL autoantibodies and IgG apoB-IC were positively associated. In logistic regression analysis, compared to the first quartile, patients in the fourth quartile of IgM OxLDL autoantibodies and ApoB-IC showed a lower probability of angiographically-determined CAD (> 50% diameter stenosis) [Odds ratios (95% confidence intervals: MDA-LDL:0.51 (0.32-0.82, P=0.005), CuOxLDL:0.63 (0.39-1.01, P=0.05), OxCL:0.63 (0.39-1.01, P=0.05), ApoB-IC:0.55 (0.34-0.88, P-0.013). These relationships were accentuated in the setting of hypercholesterolemia with the highest IgM levels showing the lowest risk of CAD for the same level of hypercholesterolemia. Multivariable analysis revealed that neither IgM or IgG OxLDL AB and apoB-IC were independently associated with angiographically-determined CAD or cardiovascular events. In conclusion, IgG and IgM OxLDL biomarkers have divergent associations with CAD in univariate analysis but are not independent predictors of CAD or clinical events.


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