title: Prognostic utility of secretory phospholipase A(2) in patients with stable coronary artery disease.
abstract: BACKGROUND
  Secretory phospholipase A(2) (sPLA(2)) may contribute to atherogenesis. To date, few prospective studies have examined the utility of sPLA(2) for risk stratification in coronary artery disease (CAD).
  
  
  METHODS
  We measured plasma sPLA(2) activity at baseline in 3708 subjects in the PEACE randomized trial of trandolapril vs placebo in stable CAD. Median follow-up was 4.8 years. We used Cox regression to adjust for demographics, clinical risk factors, apolipoprotein B, apolipoprotein A1, and medications.
  
  
  RESULTS
  After multivariable adjustment, sPLA(2) was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio Q4:Q1 1.55, 95% CI 1.13-2.14) and cardiovascular death or heart failure (1.91, 1.20-3.03). In further multivariable assessment, increased activity levels of sPLA(2) were associated with the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio 1.47, 95% CI 1.06-2.04), independent of lipoprotein-associated phospholipase A(2) mass and C-reactive protein, and modestly improved the area under the curve (AUC) beyond established clinical risk factors (AUC 0.668-0.675, P = 0.01). sPLA(2), N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T all were independently associated with cardiovascular death or heart failure, and each improved risk discrimination (P = 0.02, P < 0.001, P < 0.001, respectively).
  
  
  CONCLUSIONS
  sPLA(2) activity provides independent prognostic information beyond established risk markers in patients with stable CAD. These data are encouraging for studies designed to evaluate the role of sPLA(2) as a therapeutic target.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02215, USA. modonoghue@partners.org
authors.forename: Michelle L
authors.initials: ML
authors.lastname: O'Donoghue
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
authors.forename: Joelle
authors.initials: J
authors.lastname: Benessiano
authors.forename: Sarah
authors.initials: S
authors.lastname: Sloan
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Omland
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000401:mortality; D004796:Clinical Enzyme Tests; D003327:Coronary Disease / Q000188:drug therapy / Q000201:enzymology*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000175:diagnosis; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000175:diagnosis; D009336:Necrosis; D054497:Phospholipases A2, Secretory / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D020521:Stroke / Q000175:diagnosis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D007211:Indoles; C052035:trandolapril; D054497:Phospholipases A2, Secretory