Abstract 4998: Elevated Oxidized Phospholipids on Apolipoprotein B-100 Particles Predict 6-Year Cardiovascular Events in the Epic-Norfolk Study: Potentiation of Risk with Lipoprotein-Associated (Lp-PLA2) and Soluble Phospholipase A2 (sPLA2) Activity
Objective: We aimed to assess whether oxidized phospholipids on apoB-100 particles (OxPL/apoB) predict future coronary heart disease (CHD) in the prospective EPIC-Norfolk cohort of apparently healthy men and women aged 45–79 years followed up 1993–2007.
Methods and Results: Cases who developed CHD during follow-up were matched to controls who remained free of cardiovascular disease and who matched to cases by sex, age and enrollment time. OxPL/apoB levels were measured with antibody E06 in 905 cases and 1809 controls. Subjects in the highest quartile of OxPL/apoB at entry in the study had significantly higher risk of future CHD events (OR 1.72, 95%CI 1.32–2.24, p<0.0001) compared to those in the lowest quartile. This relationship was present in both men and women and was also observed after adjustment for sex, age, diabetes, smoking, blood pressure, LDL-C, HDL-C and Framingham Risk Score (FRS). The risk of future CHD events was significantly potentiated by elevated activity levels of sPLA2 and Lp-PLA2. Subjects in the highest tertiles of both OxPL/apoB and LpPLA2 (OR 2.22 [1.51–3.27]) or OxPL/apoB and sPLA2 (OR 4.34 [2.84 – 6.64]) had significantly higher risk of future CHD than subjects in the lowest tertiles (p<0.0001 for both). Area under receiver operating curves revealed significantly increased values by adding OxPL/apoB and sPLA2 to traditional risk factors and the FRS. Strong inverse associations were noted between the OxPL/apoB and VLDL and IDL size, CETP mass and RANK Ligand.
Conclusion: Elevated OxPL/apoB levels are a strong, independent predictor of CHD events. The predictive values is further enhanced by elevated activity levels of sPLA2 and Lp-PLA2, which mediate breakdown of OxPL present on lipoproteins and within atherosclerotic lesions. This study links several pathophysiologically related oxidative biomarkers in the prediction of CHD events and suggests novel approaches to predicting CHD risk in apparently health men and women.