BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the 
degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in 
mouse liver has been shown to decrease with fenofibrate treatment.
METHODS: We developed a sandwich ELISA using recombinant human PCSK9 protein and 
2 affinity-purified polyclonal antibodies directed against human PCSK9. We 
measured circulating PCSK9 concentrations in 115 diabetic patients from the 
FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study before and 
after fenofibrate treatment.
RESULTS: We found that plasma PCSK9 concentrations correlate with total (r = 
0.45, P = 0.006) and LDL (r = 0.54, P = 0.001) cholesterol but not with 
triglycerides or HDL cholesterol concentrations in that cohort. After 6 weeks of 
treatment with comicronized fenofibrate (200 mg/day), plasma PCSK9 
concentrations decreased by 8.5% (P = 0.041 vs pretreatment). This decrease 
correlated with the efficacy of fenofibrate, as judged by a parallel reduction 
in plasma triglycerides (r = 0.31, P = 0.015) and LDL cholesterol concentrations 
(r = 0.27, P = 0.048).
CONCLUSIONS: We conclude that this decrease in PCSK9 explains at least in part 
the LDL cholesterol-lowering effects of fenofibrate. Fenofibrate might be of 
interest to further reduce cardiovascular risk in patients already treated with 
a statin.