Abstract 170: Statin Therapy Increases Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Hypercholesterolemic Subjects

Abstract

Background PCSK9 is a secreted glycoprotein that modulates low density lipoprotein cholesterol (LDL-C) levels by negatively regulating LDL receptor (LDLR). In humans, gain of function mutations in PCSK9 increase LDL-C and loss of function mutations reduce LDL-C levels. We hypothesized that PCSK9 may be regulated by statin therapy. Objective The aim of this study was to determine the effect of pravastatin and atorvastatin on plasma PCSK9 levels in healthy subjects with hypercholesterolemia Methods & Results Hypercholesterolemic subjects (n=94) were randomized in a double blind, placebo controlled study to pravastatin 40mg/day (n=21), atorvastatin 10mg/day (n=26), atorvastatin 80mg/day (n=25), or placebo (n=22) and treated for 16 weeks. Plasma PCSK9 levels were measured using a sandwich ELISA at baseline and 16weeks. There were no significant changes in plasma PCSK9 in the placebo & atorvastatin 10 mg group. In comparison to baseline, after 16 weeks of treatment we observed a 42 % increase (247 ± 19 ng/ml to 317 ± 19 ng/ml, p value <0.05) with pravastatin 40mg/day, and a 28.4% increase (286 ± 15 ng/ml to 353.5±17 ng/ml, p value <0.05) with atorvastatin 80 mg/day in plasma PCSK9 levels. Conclusion In this randomized, placebo-controlled trial, we found a significant increase in plasma PCSK9 levels induced by pravastatin and atorvastatin. These results suggests a possible explanation for diminished LDL-C lowering with increasing doses of statin therapy.