title: Changes in lipoprotein-Associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study.
abstract: BACKGROUND
  Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with coronary heart disease (CHD) in healthy individuals and in patients who have had ischemic events.
  
  
  RESULTS
  The Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study randomized 9014 patients with cholesterol levels of 4.0 to 7.0 mmol/L to placebo or pravastatin 3 to 36 months after myocardial infarction or unstable angina and showed a reduction in CHD and total mortality. We assessed the value of baseline and change in Lp-PLA2 activity to predict outcomes over a 6-year follow-up, the effect of pravastatin on Lp-PLA2 levels, and whether pravastatin treatment effect was related to Lp-PLA2 activity change. Lp-PLA2 was measured at randomization and 1 year, and levels were grouped as quartiles. The prespecified end point was CHD death or nonfatal myocardial infarction. Baseline Lp-PLA2 activity was positively associated with CHD events (P < 0.001) but not after adjustment for 23 baseline factors (P = 0.66). In 6518 patients who were event free at 1 year, change in Lp-PLA2 was a significant independent predictor of subsequent CHD events after adjustment for these risk factors, including LDL cholesterol and LDL cholesterol changes (P < 0.001). Pravastatin reduced Lp-PLA2 by 16% compared with placebo (P < 0.001). After adjustment for Lp-PLA2 change, the pravastatin treatment effect was reduced from 23% to 10% (P = 0.26), with 59% of the treatment effect accounted for by changes in Lp-PLA2. Similar reductions in treatment effect were seen after adjustment for LDL cholesterol change.
  
  
  CONCLUSIONS
  Reduction in Lp-PLA2 activity during the first year was a highly significant predictor of CHD events, independent of change in LDL cholesterol, and may account for over half of the benefits of pravastatin in the LIPID study.
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: John
authors.initials: J
authors.lastname: Simes
authors.forename: Ralph A H
authors.initials: RA
authors.lastname: Stewart
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Barnes
authors.forename: Ian C
authors.initials: IC
authors.lastname: Marschner
authors.forename: Peter
authors.initials: P
authors.lastname: Thompson
authors.forename: Malcolm
authors.initials: M
authors.lastname: West
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.forename: David M
authors.initials: DM
authors.lastname: Colquhoun
authors.forename: Paul
authors.initials: P
authors.lastname: Nestel
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Keech
authors.forename: David R
authors.initials: DR
authors.lastname: Sullivan
authors.forename: David
authors.initials: D
authors.lastname: Hunt
authors.forename: Andrew
authors.initials: A
authors.lastname: Tonkin
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood* / Q000187:drug effects; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000097:blood* / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D013997:Time Factors
chemical_list: D000924:Anticholesteremic Agents; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D017035:Pravastatin
keywords: LIPID; Lp‐PLA2; biomarkers; pravastatin