Oxidized phospholipids potentiate Lp(a) coronary risk two-fold when combined with high phospholipase A2 activity, an EPIC-Norfolk study of 763 cases and 1397 controls (J Am Coll Cardiol 2010)

Original title: Oxidation-specific biomarkers, lipoprotein(a), and risk of fatal and nonfatal coronary events

J Am Coll Cardiol · 14 September 2010 · 8

Tsimikas S, Mallat Z, Talmud PJ, Kastelein JJ, Wareham NJ, Sandhu MS, Miller ER, Benessiano J, Tedgui A, Witztum JL, Khaw KT, Boekholdt SM

This nested case-control study within the EPIC-Norfolk cohort of 45-79-year-olds followed for about 6 years measured oxidized phospholipids on apoB-100 and Lp(a) in 763 people who developed fatal or nonfatal coronary artery disease (CAD) and 1,397 matched controls. After adjustment for standard risk factors, the highest tertiles of oxidized phospholipids on apoB-100 and Lp(a) were each associated with significantly higher CAD risk (odds ratios 1.67 and 1.64, both P<0.001) compared with the lowest tertiles. This risk was roughly doubled when combined with the highest tertile of secretory phospholipase A2 activity and mass, with a smaller potentiating effect from myeloperoxidase and lipoprotein-associated phospholipase A2. Adding these oxidation-specific biomarkers progressively improved the C-index beyond the Framingham Risk Score. The findings link oxidation-specific biomarkers and Lp(a) to CAD events, showing they add cumulative predictive value beyond traditional risk factors.

Original abstract

Objectives: 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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.