Oxidation-specific biomarkers, lipoprotein(a), and risk of fatal and nonfatal coronary events.
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.
Tsimikas
Sotirios
S
Vascular Medicine Program, University of California San Diego, La Jolla, California 92993-0682, USA. stsimikas@ucsd.edu
Mallat
Ziad
Z
Talmud
Philippa J
PJ
Kastelein
John J P
JJ
Wareham
Nicholas J
NJ
Sandhu
Manjinder S
MS
Miller
Elizabeth R
ER
Benessiano
Joelle
J
Tedgui
Alain
A
Witztum
Joseph L
JL
Khaw
Kay-Tee
KT
Boekholdt
S Matthijs
SM
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
D053299:Apolipoprotein B-100; D015415:Biomarkers; D017270:Lipoprotein(a); D010743:Phospholipids; D009195:Peroxidase; D054501:Group II Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase