Low levels of IgG autoantibodies against the apolipoprotein B antigen p210 increases the risk of cardiovascular death after carotid endarterectomy

Atherosclerosis. 2015 Apr;239(2):289-94. doi: 10.1016/j.atherosclerosis.2015.01.023. Epub 2015 Jan 28.

Abstract

Objectives: Autoimmune responses against oxidized-LDL (oxLDL) have been suggested to modulate inflammation in atherosclerosis. Previous studies showed an association between autoantibodies against the apolipoprotein B (apoB) p210 antigen and a lower risk of cardiovascular (CV) events. In the present study we investigated if autoantibodies against p210 at the time of carotid endarterectomy (CEA) predict risk for future CV events.

Methods: Native (nat) and malondialdehyde (MDA)-modified apoB p210 autoantibodies (IgM-p210nat, IgG-p210nat, IgM-p210MDA and IgG-p210MDA) were analyzed by ELISA from plasma samples of 351 patients at the time they underwent CEA. The incidence of postoperative CV events was assessed using national registers.

Results: A total of 52 non-fatal and 15 fatal CV events were registered during the follow-up period (35.1 ± 16.7 months). Patients who suffered from a fatal CV event had significantly lower plasma levels of IgG-p210nat and IgG-p210MDA. Kaplan-Meier curves of event-free survival showed increased CV mortality in patients with levels of IgG-p210nat and IgG-p210MDA below the median (Log Rank 7.813, p .005 and 9.105, p .003 respectively). The association between low levels of p210 IgG and fatal post-operative CV events remained significant when adjusting for age, sex, total cholesterol, HDL cholesterol, smoking habits and hypertension in a Cox Proportional Hazard model (hazard ratios (HR) IgG-p210nat below median: HR 6.7 (95% C.I. 1.5-30.6, p .013) and IgG-p210MDA below median: HR 7.8 (95% C.I. 1.7-35.5, p .008).

Conclusions: The present findings support the notion that autoantibodies against LDL antigens are involved in the atherosclerotic disease process and suggest that CEA patients with low levels of IgG-p210nat and IgG-p210MDA have an increased risk of post-operative CV death.

Keywords: Apolipoprotein B; Autoantibodies; Cardiovascular events; Carotid stenosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens / chemistry
  • Apolipoprotein B-100 / blood*
  • Apolipoprotein B-100 / immunology
  • Atherosclerosis / physiopathology
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / immunology*
  • Cardiovascular Diseases / physiopathology
  • Carotid Arteries / pathology
  • Carotid Stenosis / physiopathology
  • Constriction, Pathologic / physiopathology
  • Disease-Free Survival
  • Endarterectomy, Carotid*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / chemistry
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Kaplan-Meier Estimate
  • Lipoproteins, LDL / chemistry
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Risk
  • Treatment Outcome

Substances

  • APOB protein, human
  • Antigens
  • Apolipoprotein B-100
  • Autoantibodies
  • Epitopes
  • Immunoglobulin G
  • Lipoproteins, LDL
  • oxidized low density lipoprotein