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)
(2018) In EBioMedicine 36. p.63-72- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2018-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 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
- in
- EBioMedicine
- volume
- 36
- pages
- 63 - 72
- publisher
- Elsevier
- external identifiers
-
- pmid:30131305
- scopus:85051660036
- ISSN
- 2352-3964
- DOI
- 10.1016/j.ebiom.2018.08.023
- language
- English
- LU publication?
- yes
- additional info
- © 2018 The Authors. Published by Elsevier B.V.
- id
- e64e7174-505b-4200-883f-e04466b6b410
- date added to LUP
- 2020-01-22 00:13:25
- date last changed
- 2024-04-17 04:14:38
@article{e64e7174-505b-4200-883f-e04466b6b410, abstract = {{<p>Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.</p><p>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.</p><p>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.</p><p>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.</p><p>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.</p>}}, author = {{van den Berg, Victor J and Haskard, Dorian O and Fedorowski, Artur and Hartley, Adam and Kardys, Isabella and Caga-Anan, Mikhail and Akkerhuis, K Martijn and Oemrawsingh, Rohit M and van Geuns, Robert Jan and de Jaegere, Peter and van Mieghem, Nicolas and Regar, Evelyn and Ligthart, Jurgen M R and Umans, Victor A W M and Serruys, Patrick W and Melander, Olle and Boersma, Eric and Khamis, Ramzi Y}}, issn = {{2352-3964}}, keywords = {{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}}, language = {{eng}}, pages = {{63--72}}, publisher = {{Elsevier}}, series = {{EBioMedicine}}, title = {{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)}}, url = {{http://dx.doi.org/10.1016/j.ebiom.2018.08.023}}, doi = {{10.1016/j.ebiom.2018.08.023}}, volume = {{36}}, year = {{2018}}, }