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)

Abstract

BackgroundCertain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.ObjectivesWe 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.MethodsNORDIL 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.FindingsFrom 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.InterpretationOur 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.

Low Level Antibodies Against Alpha-Tropomyosin Are Associated With Increased Risk of Coronary Heart Disease

“…The relationship between TC and candidate autoantibody levels were analyzed, and there was a significant inverse correlation in anti-TPM1 antibodies (P = 0.0034, r = −0.03883) (Figures 5A-C). The same relationship was noticed for low density lipoprotein cholesterol (Ueba et al, 2009;van den Berg et al, 2018) (P = 0.0086, r = −0.04635) (Figures 5D-F).…”

“…A high concentration of G6PI was observed on the synovial lining surface and the small artery endothelial cell surface. Whether the same mechanism exists in CHD is worthy of further study (van Boekel et al, 2001). However, this is enough to show that CHD has the property of autoimmunity.…”

Anti-Oxidized LDL Antibodies and Coronary Artery Disease: A Systematic Review

“…A total of 11 cross-sectional studies were identified that explored the association between the degree of CAD, as quantified by CAG, intravascular ultrasound (IVUS) or near-infrared spectroscopy (NIRS) and IgG oxLDL autoantibodies [15,18,22,23,24,25,26,27,28,29,30], whilst five studies evaluated the relationship with IgM oxLDL autoantibodies [18,22,25,26,30]. Nine of these studies investigated all consecutive patients undergoing clinically indicated CAG [15,18,22,23,24,26,28,29,30], one study included only women undergoing CAG [25], and one study included solely patients with ST-segment elevation MI (STEMI) [27]. The endpoints were defined as number of diseased coronary arteries [18,23,26,27,29]; the Gensini score [24]; the Duke score [15] (both being composite scores for CAD lesion location and severity); a custom angiographic severity score [25]; or plaque characteristics determined by IVUS and lipid core burden index (LCBI) measured by NIRS, both measured in a non-culprit vessel [22].…”

“…Nine of these studies investigated all consecutive patients undergoing clinically indicated CAG [15,18,22,23,24,26,28,29,30], one study included only women undergoing CAG [25], and one study included solely patients with ST-segment elevation MI (STEMI) [27]. The endpoints were defined as number of diseased coronary arteries [18,23,26,27,29]; the Gensini score [24]; the Duke score [15] (both being composite scores for CAD lesion location and severity); a custom angiographic severity score [25]; or plaque characteristics determined by IVUS and lipid core burden index (LCBI) measured by NIRS, both measured in a non-culprit vessel [22]. Two studies divided their CAG patients in groups with at least one stenosis >50% and a group without stenosis >50%, and compared these two groups with healthy individuals [28,30].…”

“…Except for Che et al [24] and Gruzdeva et al [27], nine studies described a non-significant association between IgG anti-oxLDL antibodies or anti-MDA-LDL antibodies and the severity of CAD, as quantified at CAG [15,18,22,23,25,26,28,29,30]. Che et al [24] found a negative association between the natural logarithm of the (Gensini-score + 1) and serum IgG anti-oxLDL autoantibodies in 154 consecutive CAG patients.…”