title: Impact of plasma Lp-PLA2 activity on the progression of aortic stenosis: the PROGRESSA study.
abstract: OBJECTIVE
  The purpose of this prospective study was to examine the relationship between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and the progression rate of aortic stenosis (AS).
  
  
  BACKGROUND
  We recently reported that Lp-PLA2 is highly expressed in stenotic aortic valves where it may contribute to the mineralization of valvular interstitial cells.
  
  
  METHODS
  Patients with AS were prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study. AS progression rate was assessed by annualized increase in peak aortic jet velocity (Vpeak), mean gradient (MG), and aortic valve area index (AVAi). Circulating Lp-PLA2 activity was measured and dichotomized based on the median value.
  
  
  RESULTS
  Of 183 patients included in this subanalysis of the PROGRESSA study, 70% were men and the mean age was 66 ± 13 years. Over the 2.5 ± 1.4 years of follow up, the AS progression rate tended to be higher in patients with high versus low Lp-PLA2 activity (annualized Vpeak = 0.17 ± 0.23 m/s vs. 0.12 ± 0.18 m/s; p = 0.14). There was a significant interaction (p < 0.05) between baseline AS severity and Lp-PLA2 activity with respect to impact on AS progression rate. In patients with mild AS (i.e., Vpeak <3 m/s; n = 123), increased Lp-PLA2 activity was associated with a significantly faster AS progression rate (Vpeak 0.16 ± 0.18 m/s vs. 0.09 ± 0.14 m/s; p = 0.01) but not in patients with moderate or severe AS (p = 0.99). After adjustment for other risk factors, increased Lp-PLA2 activity remained independently associated with faster AS progression rate (p = 0.005) in the former subset.
  
  
  CONCLUSIONS
  There was no significant association between plasma Lp-PLA2 activity or mass and stenosis progression in the whole cohort. However, increased Lp-PLA2 activity was associated with a faster stenosis progression rate in the subset of patients with mild AS. These findings provide an impetus for the elaboration of a randomized trial targeting Lp-PLA2 activity in patients with early stages of calcific aortic valve disease.
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: Ablajan
authors.initials: A
authors.lastname: Mahmut
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Lionel
authors.initials: L
authors.lastname: Tastet
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
authors.initials: M
authors.lastname: Arsenault
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
authors.forename: Élisabeth
authors.initials: É
authors.lastname: Bédard
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: 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.
authors.forename: Éric
authors.initials: É
authors.lastname: Larose
authors.affiliation: 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: 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: 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: 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: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000368:Aged; D001021:Aortic Valve / Q000473:pathology / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000503:physiopathology*; D018450:Disease Progression; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D016277:Ventricular Function, Left
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase
keywords: Doppler echocardiography; aortic stenosis; calcific aortic valve disease; lipoprotein-associated phospholipase A2