title: Human IgM Antibodies to Malondialdehyde Conjugated With Albumin Are Negatively Associated With Cardiovascular Disease Among 60-Year-Olds.
abstract: Malondialdehyde (MDA) is generated during lipid peroxidation as in oxidized low-density lipoprotein, but antibodies against oxidized low-density lipoprotein show variable results in clinical studies. We therefore studied the risk of cardiovascular disease (CVD) associated with IgM antibodies against MDA conjugated with human albumin (anti-MDA).
  
  
  
  In a 5- to 7-year follow-up of 60-year-old men and women from Stockholm County previously screened for cardiovascular risk factors (2039 men, 2193 women), 209 incident CVD cases (defined as new events of coronary heart disease, fatal and nonfatal myocardial infarction, ischemic stroke, and hospitalization for angina pectoris) and 620 age- and sex-matched controls were tested for IgM anti-MDA by ELISA. Antibody peptide/protein characterization was done using a proteomics de novo sequencing approach. After adjustment for smoking, body-mass index, type 2 diabetes mellitus, hyperlipidemia, and hypertension, an increased CVD risk was observed in the low IgM anti-MDA percentiles (below 10th and 25th) (odds ratio and 95% CI: 2.0; 1.19-3.36 and 1.67; 1.16-2.41, respectively). Anti-MDA above the 66th percentile was associated with a decreased CVD risk (odds ratio 0.68; CI: 0.48-0.98). After stratification by sex, associations were only present among men. IgM anti-MDA levels were lower among cases (median [interquartile range]: 141.0 [112.7-164.3] versus 147.4 [123.5-169.6]; P=0.0177), even more so among men (130.6 [107.7-155.3] versus 143.0 [120.1-165.2]; P=0.001). The IgM anti-MDA variable region profiles are distinctly different and also more homologous in their content (correlates strongly with fewer peptides) than control antibodies (not binding MDA).
  
  
  
  IgM anti-MDA is a protection marker for CVD. This finding could have diagnostic and therapeutic implications.
authors.affiliation: Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Divya
authors.initials: D
authors.lastname: Thiagarajan
authors.affiliation: Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Frostegård
authors.affiliation: Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Singh
authors.affiliation: Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mizanur
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anquan
authors.initials: A
authors.lastname: Liu
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Max
authors.initials: M
authors.lastname: Vikström
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Leander
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Cardiovascular Clinical Science, Danderyds Hospital Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bruna
authors.initials: B
authors.lastname: Gigante
authors.affiliation: Department of Medicine, Karolinska University Hospital, Solna, Sweden.
authors.forename: Mai-Lis
authors.initials: ML
authors.lastname: Hellenius
authors.affiliation: Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Zubarev
authors.affiliation: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Cardiology, Karolinska University Hospital, Solna, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.affiliation: Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Lundström
authors.affiliation: Unit of Immunology and Chronic Disease, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden johan.frostegard@ki.se.|Division of Emergency Medicine, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Frostegård
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000453:epidemiology / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000276:immunology*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D015994:Incidence; D008297:Male; D008315:Malondialdehyde / Q000276:immunology*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000276:immunology; D011446:Prospective Studies; D012709:Serum Albumin / Q000276:immunology*; D020521:Stroke / Q000453:epidemiology / Q000276:immunology; D013548:Sweden / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D007075:Immunoglobulin M; D012709:Serum Albumin; D008315:Malondialdehyde
keywords: antibody; cardiovascular disease; cardiovascular disease risk factors; immune system; malondialdehyde; oxidation; proteomics