IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)

Research output: Contribution to journalArticle


Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.

Objectives: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics.

Methods: NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386?days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively.

Findings: From 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p=0.012; p=0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p=0.027) and percentage of plaque occupied by necrotic core (p=0.011), as well as lipid core burden index (p=0.024) in the worst 4 mm segment.

Interpretation: Our study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.


  • Victor J van den Berg
  • Dorian O Haskard
  • Artur Fedorowski
  • Adam Hartley
  • Isabella Kardys
  • Mikhail Caga-Anan
  • K Martijn Akkerhuis
  • Rohit M Oemrawsingh
  • Robert Jan van Geuns
  • Peter de Jaegere
  • Nicolas van Mieghem
  • Evelyn Regar
  • Jurgen M R Ligthart
  • Victor A W M Umans
  • Patrick W Serruys
  • Olle Melander
  • Eric Boersma
  • Ramzi Y Khamis
External organisations
  • Erasmus University Medical Center
  • Imperial College London
  • Skåne University Hospital
  • Northwest Hospital Group, Alkmaar
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems


  • Aged, Atherosclerosis/blood, Biomarkers/blood, Coronary Artery Disease/blood, Female, Humans, Immunoglobulin M/blood, Lipoproteins, LDL/immunology, Male, Malondialdehyde/analogs & derivatives, Middle Aged, Necrosis/blood, Prospective Studies
Original languageEnglish
Pages (from-to)63-72
Publication statusPublished - 2018 Oct
Publication categoryResearch