title: Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events.
abstract: 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.
authors.affiliation: Division of Cardiovascular Diseases, University of California, San Diego, CA, USA. stsimikas@ucsd.edu
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
authors.forename: Emmanouil S
authors.initials: ES
authors.lastname: Brilakis
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Lennon
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Miller
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McConnell
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kornman
authors.forename: Peter B
authors.initials: PB
authors.lastname: Berger
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000097:blood* / Q000276:immunology; D003300:Copper; D003324:Coronary Artery Disease / Q000097:blood* / Q000276:immunology; D023921:Coronary Stenosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000276:immunology; D008297:Male; D008315:Malondialdehyde; D008875:Middle Aged; D016017:Odds Ratio; D012306:Risk
chemical_list: D001055:Apolipoproteins B; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde; D003300:Copper