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 in Context

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 unfa...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2018-10-01
Series:EBioMedicine
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396418303098
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Summary: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. Keywords: Necrotic core, Lipid core, Oxidized low density lipoprotein, Immunoglobulins, Near-infrared spectroscopy, Intravascular ultrasound
ISSN:2352-3964