title: Circulating levels of matrix gla protein and progression of aortic stenosis: a substudy of the Aortic Stenosis Progression Observation: Measuring Effects of rosuvastatin (ASTRONOMER) trial.
abstract: BACKGROUND
  Matrix γ-carboxyglutamate protein is an inhibitor of cardiovascular calcification. The objective of this substudy of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial was to examine the relationship between total (ie, carboxylated [active] form + uncarboxylated [inactive] form) circulating desphosphorylated matrix γ-carboxyglutamate protein (dpMGP) level and the progression rate of aortic stenosis (AS).
  
  
  METHODS
  Among the patients included in the ASTRONOMER trial, 215 patients had measures of baseline circulating total dpMGP level and an echocardiographic follow-up (mean follow-up: 3.5 ± 1.3 years). Progression of AS was assessed according to the measurement of the annualized increase in peak aortic jet velocity.
  
  
  RESULTS
  In the whole cohort, baseline dpMGP level was associated with faster progression rate of peak aortic jet velocity (r = 0.16; P = 0.02) in individual analysis but not in multivariable analysis (P = 0.40). However, there was a significant interaction (P = 0.03) between dpMGP level and age, with respect to the effect on AS progression. After dichotomization according to median value of age (ie, 57 years old), total dpMGP level was associated with faster AS progression rate (r = 0.24; P = 0.008) in the younger patients, and this association remained significant in multivariable analysis (P = 0.04), but not in the older ones. The independent correlates of dpMGP level were fasting glucose (P = 0.009) and oxidized low-density lipoprotein (P = 0.01).
  
  
  CONCLUSIONS
  This is the first prospective study to demonstrate a relationship between increased circulating levels of total dpMGP and faster progression rate of AS in younger individuals. Future studies are needed to determine if dpMGP is simply a marker or a contributing factor to ectopic mineralization of aortic valve.
authors.affiliation: 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: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Côté
authors.affiliation: 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: University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Kwan L
authors.initials: KL
authors.lastname: Chan
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Marie-Annick
authors.initials: MA
authors.lastname: Clavel
authors.affiliation: 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: McMaster University, Hamilton, Ontario, Canada.
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
authors.affiliation: St Boniface General Hospital, Winnipeg, Manitoba, Canada.
authors.forename: James W
authors.initials: JW
authors.lastname: Tam
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Dominique
authors.initials: D
authors.lastname: Fournier
authors.affiliation: 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: 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
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D001024:Aortic Valve Stenosis / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D002135:Calcium-Binding Proteins / Q000097:blood; D018450:Disease Progression; D015150:Echocardiography, Doppler; D016326:Extracellular Matrix Proteins / Q000097:blood; D005464:Fluorobenzenes / Q000627:therapeutic use; D000097568:Matrix Gla Protein; D015999:Multivariate Analysis; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D005464:Fluorobenzenes; D000097568:Matrix Gla Protein; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides