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Journal of Lipid Research, Vol. 48, 425-433, February 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events

Sotirios Tsimikas^1,*, Emmanouil S. Brilakis, Ryan J. Lennon, Elizabeth R. Miller^**, Joseph L. Witztum^**, Joseph P. McConnell, Kenneth S. Kornman and Peter B. Berger^***

^* Division of Cardiovascular Diseases, University of California, San Diego, CA
^** Division of Endocrinology and Metabolism, University of California, San Diego, CA
University of Texas Southwestern Medical Center and North Texas Veterans Affairs Medical Center, Dallas, TX
Division of Cardiovascular Diseases and Biostatistics, Mayo Clinic, Rochester, MN
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
Interleukin Genetics, Waltham, MA
^*** Division of Cardiovascular Medicine, Geisinger Center for Health Research, Danville, PA

Published, JLR Papers in Press, November 8, 2006.

¹ To whom correspondence should be addressed. e-mail: stsimikas{at}ucsd.edu

The relationship between autoantibodies to oxidized low density lipoprotein (OxLDL) and coronary artery disease (CAD) remains controversial. IgM and IgG OxLDL autoantibodies to malondialdehyde (MDA)-modified LDL, copper oxidized low density lipoprotein (CuOxLDL), and oxidized cholesterol linoleate (OxCL), as well as apolipoprotein B-100 immune complexes (apoB-ICs), 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-ICs were inversely associated with the presence of angiographically determined CAD, whereas IgG OxLDL autoantibodies and IgG apoB-ICs were positively associated. In logistic regression analysis, compared with the first quartile, patients in the fourth quartile of IgM OxLDL autoantibodies and apoB-ICs showed a lower probability of angiographically determined CAD (>50% diameter stenosis). Odds ratios and (95% confidence intervals) were as follows: 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); and 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 autoantibodies nor apoB-ICs 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.

Supplementary key words angiography • atherosclerosis • antibodies • lipoproteins • oxidation

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