Autoantibodies and immune complexes to oxidation-specific epitopes and progression of aortic stenosis: Results from the ASTRONOMER trial

Atherosclerosis. 2017 May:260:1-7. doi: 10.1016/j.atherosclerosis.2017.03.013. Epub 2017 Mar 9.

Abstract

Background and aims: Elevated levels of lipoprotein(a) [Lp(a)] and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) predict the progression of pre-existing mild-to-moderate calcific aortic valve stenosis (CAVS). Whether indirect markers of oxidation-specific epitopes (OSE) are also predictive is not known. The association between IgG and IgM autoantibodies and malondialdehyde-modified low density lipoprotein (MDA-LDL) and IgG and IgM apolipoprotein B immune complexes (apoB-IC), and the hemodynamic progression rate of CAVS was determined in the ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin, NCT00800800) trial.

Methods: Plasma levels of IgG and IgM MDA-LDL and apoB-IC were measured in 220 patients with mild-to-moderate CAVS from the ASTRONOMER trial. The endpoint of this study was the progression rate of CAVS, measured by the annualized increase in peak aortic jet velocity (Vpeak) over a median follow-up of 3.5 [2.9-4.5] years.

Results: There was no difference in the progression rate of CAVS across tertiles of IgG and IgM MDA-LDL and apoB-IC levels (all p > 0.05). After multivariable analysis, no marker reached significance level to predict faster CAVS progression or need for aortic valve replacement (all p > 0.05). There was no interaction between the OSE antibody titers and plasma levels of Lp(a) or OxPL-apoB, as well as age, with regards to the progression rate of CAVS.

Conclusions: Autoantibody titers to MDA-LDL and apoB-IC, which are an indirect measurement of OSE, unlike direct measurements of OxPL-apoB or their major lipoprotein carrier Lp(a), do not predict the progression of CAVS or need for AVR.

Keywords: Aortic stenosis; Calcific aortic valve stenosis; Doppler echocardiography; Lipoprotein(a); Oxidation-specific biomarkers.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Anti-Idiotypic / blood*
  • Antibodies, Anti-Idiotypic / immunology
  • Aortic Valve / immunology
  • Aortic Valve / pathology*
  • Aortic Valve Stenosis / complications
  • Aortic Valve Stenosis / drug therapy
  • Aortic Valve Stenosis / etiology
  • Aortic Valve Stenosis / immunology*
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers / blood
  • Calcinosis / complications*
  • Calcinosis / drug therapy
  • Calcinosis / immunology
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Epitopes
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / blood*
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Retrospective Studies
  • Rosuvastatin Calcium / administration & dosage*
  • Time Factors
  • Young Adult

Substances

  • Antibodies, Anti-Idiotypic
  • Autoantibodies
  • Biomarkers
  • Epitopes
  • Immunoglobulin G
  • Rosuvastatin Calcium

Supplementary concepts

  • Aortic Valve, Calcification of

Associated data

  • ClinicalTrials.gov/NCT00800800