title: Oxidation-specific biomarkers, lipoprotein(a), and risk of fatal and nonfatal coronary events.
abstract: OBJECTIVE
  This study sought to assess whether oxidation-specific biomarkers are associated with an increased risk of coronary artery disease (CAD) events.
  
  
  BACKGROUND
  The relationship of a panel of oxidative biomarkers and lipoprotein(a) [Lp(a)] to CAD risk is not fully determined.
  
  
  METHODS
  A prospective case-control study nested in the EPIC (European Prospective Investigation of Cancer)-Norfolk cohort of 45- to 79-year-old apparently healthy men and women followed for approximately 6 years was designed. Cases consisted of participants in whom fatal or nonfatal CAD developed, matched by sex, age, and enrollment time with controls without CAD. Baseline levels of oxidized phospholipids on apolipoprotein B-100 particles and Lp(a) were measured in 763 cases and 1,397 controls. Their relationship to secretory phospholipase A(2) type IIA mass and activity, myeloperoxidase mass, and lipoprotein-associated phospholipase A(2) activity and association with CAD events were determined.
  
  
  RESULTS
  After adjusting for age, smoking, diabetes, low- and high-density lipoprotein cholesterol, and systolic blood pressure, the highest tertiles of oxidized phospholipids on apolipoprotein B-100 particles and Lp(a) were associated with a significantly higher risk of CAD events (odds ratios: 1.67 and 1.64, respectively; p < 0.001) compared with the lowest tertiles. The odds ratio of CAD events associated with the highest tertiles of oxidized phospholipids on apolipoprotein B-100 particles or Lp(a) was significantly potentiated (approximately doubled) by the highest tertiles of secretory phospholipase A(2) activity and mass but less so for myeloperoxidase and lipoprotein-associated phospholipase A(2) activity. The odds ratios for fatal CAD were higher than for the combined end point. After taking into account the Framingham Risk Score, c-index values progressively increased when oxidative biomarkers were added to the model.
  
  
  CONCLUSIONS
  This EPIC-Norfolk study links pathophysiologically related oxidation-specific biomarkers and Lp(a) with CAD events. Oxidation-specific biomarkers provide cumulative predictive value when added to traditional cardiovascular risk factors.
authors.affiliation: Vascular Medicine Program, University of California San Diego, La Jolla, California 92993-0682, USA. stsimikas@ucsd.edu
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Miller
authors.forename: Joelle
authors.initials: J
authors.lastname: Benessiano
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000368:Aged; D053299:Apolipoprotein B-100 / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000401:mortality*; D005260:Female; D054501:Group II Phospholipases A2 / Q000097:blood; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D016017:Odds Ratio; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000097:blood; D010743:Phospholipids / Q000097:blood; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment
chemical_list: D053299:Apolipoprotein B-100; D015415:Biomarkers; D017270:Lipoprotein(a); D010743:Phospholipids; D009195:Peroxidase; D054501:Group II Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase