title: Relationship of lipoprotein-associated phospholipase A₂ mass and activity with incident vascular events among primary prevention patients allocated to placebo or to statin therapy: an analysis from the JUPITER trial.
abstract: BACKGROUND
  Although lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with cardiovascular events, Lp-PLA(2) is physically linked to LDL cholesterol (LDL-C). Whether measures of Lp-PLA(2) mass or activity continue to predict risk after LDL-C reduction by statin therapy is uncertain.
  
  
  METHODS
  Lp-PLA(2) mass concentration and activity were evaluated at baseline and after treatment in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial comparing rosuvastatin 20 mg to placebo among 17 802 men and women without cardiovascular disease or diabetes at study entry. The relationships of Lp-PLA(2) mass and activity with risk of future vascular events were evaluated in the placebo and rosuvastatin groups.
  
  
  RESULTS
  Before randomization, levels of Lp-PLA(2) mass and activity correlated moderately with each other and with LDL-C. The magnitude of these correlations increased after statin therapy. Rosuvastatin reduced Lp-PLA(2) mass by 33.8%, Lp-PLA(2) activity by 33.2%, and LDL-C by 48.7% (all P < 0.0001). Among those study participants allocated to placebo, increasing quartiles of Lp-PLA(2) activity (P(trend) = 0.04) but not Lp-PLA(2) mass (P(trend) = 0.92) were associated with incident cardiovascular events after adjustment for LDL-C and conventional risk factors. Comparable analyses conducted among those allocated to rosuvastatin revealed no significant relationship between Lp-PLA(2) levels and subsequent vascular events. The ability of rosuvastatin to reduce vascular events was not significantly modified by baseline Lp-PLA(2) level.
  
  
  CONCLUSIONS
  Among JUPITER trial participants allocated to placebo, levels of Lp-PLA(2) activity, but not mass, were associated with cardiovascular risk. However, Lp-PLA(2) no longer predicted risk or modified clinical outcomes when participants were treated with rosuvastatin.
authors.affiliation: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, MA 02215, USA. pridker@partners.org
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Jean G
authors.initials: JG
authors.lastname: MacFadyen
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wolfert
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000368:Aged; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology* / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D011322:Primary Prevention; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase