Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Dec 2016)

Human IgM Antibodies to Malondialdehyde Conjugated With Albumin Are Negatively Associated With Cardiovascular Disease Among 60‐Year‐Olds

  • Divya Thiagarajan,
  • Anna G. Frostegård,
  • Sudhir Singh,
  • Mizanur Rahman,
  • Anquan Liu,
  • Max Vikström,
  • Karin Leander,
  • Bruna Gigante,
  • Mai‐Lis Hellenius,
  • Bo Zhang,
  • Roman A. Zubarev,
  • Ulf de Faire,
  • Susanna L. Lundström,
  • Johan Frostegård

DOI
https://doi.org/10.1161/JAHA.116.004415
Journal volume & issue
Vol. 5, no. 12

Abstract

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BackgroundMalondialdehyde (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). Methods and ResultsIn 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). ConclusionsIgM anti‐MDA is a protection marker for CVD. This finding could have diagnostic and therapeutic implications.

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