title: Lipoprotein-associated phospholipase A2 predicts 5-year cardiac mortality independently of established risk factors and adds prognostic information in patients with low and medium high-sensitivity C-reactive protein (the Ludwigshafen risk and cardiovascular health study).
abstract: BACKGROUND
  Lipoprotein-associated phospholipase A(2) (LpPLA(2)), also denoted as platelet-activating factor acetylhydrolase, is a lipoprotein-bound enzyme involved in inflammation and atherosclerosis. In this cohort study we investigated LpPLA(2) activity to predict cardiac mortality in patients scheduled for coronary angiography.
  
  
  METHODS
  LpPLA(2) activity was determined in 2513 patients with and in 719 patients without angiographically confirmed coronary artery disease (CAD).
  
  
  RESULTS
  During the median observation period of 5.5 years, 501 patients died. In patients with tertiles of LpPLA(2) activity of 420-509 U/L or >or=510 U/L, unadjusted hazard ratios (HRs) for cardiac death were 1.7 (95% CI 1.3-2.4; P = 0.001), and 1.9 (95% CI 1.4-2.5; P <0.001), respectively, compared with patients with LpPLA(2) activity <or=419 U/L. After we accounted for established risk factors and included angiographic CAD status, high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide, the 3rd tertile of LpPLA(2) activity predicted cardiac 5-year mortality with an HR of 2.0 (95% CI 1.4-3.1; P = 0.001). LpPLA(2) activity increased the adjusted risk for cardiac death by 2-fold in patients with hsCRP <3 mg/L in the 2nd (HR 2.4, 95% CI 1.4-4.2; P = 0.002) and 3rd (HR 2.1, 95% CI 1.1-4.0; P = 0.02) tertiles of LpPLA(2) activity and in patients with hsCRP of 3-10 mg/L in the 3rd tertile (HR 1.9, 95% CI 1.0-3.6; P = 0.03) of LpPLA(2) activity.
  
  
  CONCLUSIONS
  LpPLA(2) activity predicts risk for 5-year cardiac mortality independently from established risk factors and indicates risk for cardiac death in patients with low and medium-high hsCRP concentrations. Therefore, LpPLA(2) activity may provide information for the identification and management of patients at risk beyond established risk stratification strategies.
authors.affiliation: Department of Clinical Chemistry, University Medical Center Freiburg, Germany. kwinkler@ukl.uni-freiburg.de
authors.forename: Karl
authors.initials: K
authors.lastname: Winkler
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Bernhard R
authors.initials: BR
authors.lastname: Winkelmann
authors.forename: Isolde
authors.initials: I
authors.lastname: Friedrich
authors.forename: Günther
authors.initials: G
authors.lastname: Schäfer
authors.forename: Ursula
authors.initials: U
authors.lastname: Seelhorst
authors.forename: Britta
authors.initials: B
authors.lastname: Wellnitz
authors.forename: Heinrich
authors.initials: H
authors.lastname: Wieland
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Winfried
authors.initials: W
authors.lastname: März
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D003327:Coronary Disease / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054467:Phospholipases A2; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D002097:C-Reactive Protein; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase