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



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.



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.



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.
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada.
Romain
R
Capoulade
University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Kwan L
KL
Chan
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada.
Patrick
P
Mathieu
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada.
Yohan
Y
Bossé
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada.
Jean G
JG
Dumesnil
St. Boniface General Hospital, Winnipeg, Manitoba, Canada.
James W
JW
Tam
McMaster University, Hamilton, Ontario, Canada.
Koon K
KK
Teo
University of California San Diego, La Jolla, CA, USA.
Xiaohong
X
Yang
University of California San Diego, La Jolla, CA, USA.
Joseph L
JL
Witztum
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada.
Benoit J
BJ
Arsenault
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada.
Jean-Pierre
JP
Després
Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart & Lung Institute, Laval University, Québec City, Québec, Canada. Electronic address: philippe.pibarot@med.ulaval.ca.
Philippe
P
Pibarot
University of California San Diego, La Jolla, CA, USA. Electronic address: stsimikas@ucsd.edu.
Sotirios
S
Tsimikas
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000276:immunology; D001021:Aortic Valve / Q000276:immunology / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000150:complications / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012189:Retrospective Studies; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage*; D013997:Time Factors; D055815:Young Adult
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D015415:Biomarkers; D000939:Epitopes; D007074:Immunoglobulin G; D000068718:Rosuvastatin Calcium
Aortic stenosis; Calcific aortic valve stenosis; Doppler echocardiography; Lipoprotein(a); Oxidation-specific biomarkers