Abstract 1494: Paraoxonase 1 Activity Predicts Prevalence, Severity and Progression of Coronary Artery Disease at All Levels of High-Density Lipoprotein Cholesterol
INTRODUCTION: Levels of high-density lipoprotein cholesterol (HDL) inversely correlate with the incidence of coronary artery disease (CAD). The atheroprotective properties of HDL are attributed, in part, to the anti-inflammatory and antioxidant activity of associated factors including paraoxonase1 (PON1). Herein we investigated whether serum PON1 activity predicts coronary artery disease prevalence, angiographic burden, and prospective clinical events independent of HDL levels.
METHOD: Plasma samples of 1403 sequential subjects presenting for diagnostic coronary angiography were analyzed for PON1 activity using an arylesterase assay. Subjects stratified by HDL quartiles were compared with regard to the ability of serum PON1 activity to predict the presence and extent of angiographic CAD and future clinical events.
RESULTS: PON1 activity predicted both the angiographic severity of CAD and its prevalence at all HDL levels. Compared with the high quartile of PON1 activity, subjects with the low quartile were 1.8-fold (95%CI 1.2–2.5, p<0.05) and 4.5-fold (95%CI 3.4–5.6, p<0.01) more likely to have CAD (>30% stenosis of an epicardial vessel) in the low and high HDL quartiles, respectively. Subjects with the low quartile PON1 activity were 2.5-fold (95%CI 1.7–3.2, p<0.05) and 1.9-fold (95%CI 1.1–2.8, p<0.05) more likely to have three vessel CAD in the low and high HDL quartiles, respectively. Subjects with the low quartile PON1 activity were 1.8-fold (95%CI 1.2–2.5, p<0.05) and 1.9-fold (95%CI 1.1–2.7, p<0.05) more likely to have a subsequent non-fatal myocardial infarction in the low and high HDL quartiles, respectively. While the low quartile PON1 activity was associated with a 2.1-fold (95%CI 1.5–2.7, p<0.05) higher rate of major cardiac events (non-fatal MI and death) in the high HDL quartile, low PON1 activity did not predict events in subjects with the lowest HDL (OR 1.0, 95%CI 0.3–1.6).
DISCUSSION: In conclusion, low PON1 activity predicts the presence and extent of CAD in subjects, regardless of their HDL level. The ability of PON1 to predict clinical events was consistently observed in subjects with a high, but not low HDL. These results highlight the importance of HDL quality rather than quantity in determining its atheroprotective role.