Background Malondialdehyde (MDA)-LDL is one of the main oxidation products involved in atherosclerosis pathogenesis. IgM antibodies against MDA-LDL have been generally regarded as protecting from atherosclerosis. In contrast, the role of IgG antibodies is less clear. How antibody levels relate to coronary atherosclerosis plaque characteristics still needs to be determined.

Hypothesis We tested the hypothesis that low IgM anti-MDA antibody levels in serum are associated with plaques with larger lipid-laden necrotic cores.

Method IBIS-3 was a prospective cohort study that was designed to determine the ability of rosuvastatin to decrease necrotic core volume in coronary atherosclerosis. Patients undergoing coronary artery grafting or percutaneous intervention for (un)stable angina pectoris or myocardial infarction were eligible. After the standard procedure, radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS) measurements were performed in a non-culprit coronary artery with a diameter stenosis<50%. After a median of 386 days of high dose rosuvastatin treatment, imaging was repeated on the same segment. Antibodies against MDA-LDL, as well as total serum IgM and IgG, were measured by ELISA. Associations between antibodies and the RF-IVUS and NIRS parameters were assessed using linear regression models with quartiles as independent variables and with further adjustments for age, sex, diabetes, smoking, LDL and HDL cholesterol and previous use of statins.

Results A total of 143 patients of the included patients had both blood samples and RF-IVUS measurements available, and NIRS was also performed on 90 of these. Mean age was 59.6 (9.0) years (84.6% male) and 94.4% were already on a regular statin before inclusion. At baseline, IgM anti MDA-LDL antibody levels had a strong independent inverse relationship with lesional necrotic core volume (p=0.027) and percentage (p=0.011) as well as with lipid core burden index (LCBI) (p=0.024) in the worst 4 mm segment. This relationship was partially dependent on total serum IgM, as higher IgM levels also reflected a favourable necrotic core percentage on RF-IVUS. There was no correlation between any imaging parameter and IgG antibodies, total serum IgG, HDL-cholesterol or LDL-cholesterol. Although total atheroma burden increased over one year, there was no change in necrotic core volume.

Conclusion The data show that higher levels of IgM antibodies, including IgM anti-MDA, are associated with a decreased coronary necrotic core volume and lipid core burden, whereas total serum IgG and IgG anti-MDA LDL antibodies were not related to the measured plaque characteristics. The ability of IgM antibodies but not HDL- or LDL-cholesterol levels to indicate these important plaque characteristics is consistent with a proposed mechanistic role.