title: Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis.
abstract: BACKGROUND
  Elevated lipoprotein(a) (Lp[a]) is associated with aortic stenosis (AS). Oxidized phospholipids (OxPL) are key mediators of calcification in valvular cells and are carried by Lp(a).
  
  
  OBJECTIVE
  This study sought to determine whether Lp(a) and OxPL are associated with hemodynamic progression of AS and AS-related events.
  
  
  METHODS
  OxPL on apolipoprotein B-100 (OxPL-apoB), which reflects the biological activity of Lp(a), and Lp(a) levels were measured in 220 patients with mild-to-moderate AS. The primary endpoint was the progression rate of AS, measured by the annualized increase in peak aortic jet velocity in m/s/year by Doppler echocardiography; the secondary endpoint was need for aortic valve replacement and cardiac death during 3.5 ± 1.2 years of follow-up.
  
  
  RESULTS
  AS progression was faster in patients in the top tertiles of Lp(a) (peak aortic jet velocity: +0.26 ± 0.26 vs. +0.17 ± 0.21 m/s/year; p = 0.005) and OxPL-apoB (+0.26 ± 0.26 m/s/year vs. +0.17 ± 0.21 m/s/year; p = 0.01). After multivariable adjustment, elevated Lp(a) or OxPL-apoB levels remained independent predictors of faster AS progression. After adjustment for age, sex, and baseline AS severity, patients in the top tertile of Lp(a) or OxPL-apoB had increased risk of aortic valve replacement and cardiac death.
  
  
  CONCLUSIONS
  Elevated Lp(a) and OxPL-apoB levels are associated with faster AS progression and need for aortic valve replacement. These findings support the hypothesis that Lp(a) mediates AS progression through its associated OxPL and provide a rationale for randomized trials of Lp(a)-lowering and OxPL-apoB-lowering therapies in AS. (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin [ASTRONOMER]; NCT00800800).
authors.affiliation: Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Romain
authors.initials: R
authors.lastname: Capoulade
authors.affiliation: Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Kwan L
authors.initials: KL
authors.lastname: Chan
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California.
authors.forename: Calvin
authors.initials: C
authors.lastname: Yeang
authors.affiliation: Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mathieu
authors.affiliation: Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Jean G
authors.initials: JG
authors.lastname: Dumesnil
authors.affiliation: Department of Medicine, St. Boniface General Hospital, Winnipeg, Manitoba, Canada.
authors.forename: James W
authors.initials: JW
authors.lastname: Tam
authors.affiliation: Department of Medicine (Cardiology), McMaster University, Hamilton, Ontario, Canada.
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
authors.affiliation: Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Ablajan
authors.initials: A
authors.lastname: Mahmut
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.affiliation: Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Arsenault
authors.affiliation: Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Després
authors.affiliation: Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada. Electronic address: philippe.pibarot@med.ulaval.ca.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pibarot
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: stsimikas@ucsd.edu.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
mesh_terms: D000328:Adult; D000368:Aged; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000000981:diagnostic imaging* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000097:blood* / Q000000981:diagnostic imaging* / Q000401:mortality; D003643:Death; D018450:Disease Progression; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood*; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D017270:Lipoprotein(a); D010743:Phospholipids
keywords: Doppler echocardiography; aortic valve replacement; lipoprotein; peak aortic jet velocity