Plasma PCSK9 is increased by Fenofibrate and Atorvastatin in a non-additive fashion in diabetic patients

Abstract Objective Proprotein convertase subtilisin kexin/type 9 (PCSK9) is an inhibitor of the low density (LDL) lipoprotein receptor. Plasma PCSK9 is increased by Fenofibrate and statins. Here, we determined how standard dose of statin and combined therapy with Fenofibrate modulate PCSK9. Methods...

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Published in:	Atherosclerosis 2010-09, Vol.212 (1), p.246-251
Main Authors:	Costet, P, Hoffmann, M.M, Cariou, B, Delasalle, B. Guyomarc’h, Konrad, T, Winkler, K
Format:	Article
Language:	eng
Subjects:	Adult Aged Associated diseases and complications Atherosclerosis (general aspects, experimental research) Atorvastatin Calcium Biological and medical sciences Biomarkers - blood Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular Cholesterol, HDL - blood Cholesterol, LDL - blood Cross-Over Studies Diabetes Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - drug therapy Diabetes. Impaired glucose tolerance Drug Therapy, Combination Dyslipidemias - blood Dyslipidemias - drug therapy Endocrine pancreas. Apud cells (diseases) Endocrinopathies Female Fenofibrate Fenofibrate - therapeutic use France Germany HDL Heptanoic Acids - therapeutic use Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Hypolipidemic Agents - therapeutic use LDL Male Medical sciences Middle Aged PCSK9 Proprotein Convertase 9 Proprotein Convertases Pyrroles - therapeutic use Serine Endopeptidases - blood Statin Time Factors Treatment Outcome Triglyceride Triglycerides - blood Up-Regulation
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Summary:	Abstract Objective Proprotein convertase subtilisin kexin/type 9 (PCSK9) is an inhibitor of the low density (LDL) lipoprotein receptor. Plasma PCSK9 is increased by Fenofibrate and statins. Here, we determined how standard dose of statin and combined therapy with Fenofibrate modulate PCSK9. Methods Randomized, open-label cross-over study investigating the effect of Fenofibrate (160 mg), Atorvastatin (10 mg), and combination of both in patients with type 2 diabetes mellitus and atherogenic dyslipidemia. After the single administration of Atorvastatin and Fenofibrate for 6 weeks, patients received both for another 6 weeks. PCSK9, lipids and lipoproteins levels were determined at day 1, weeks 6, 9 and 12. Results Upon 6 weeks of treatment, Atorvastatin decreased LDL-cholesterol by 30% ( p < 0.001) and Fenofibrate decreased triglyceride level by 31% ( p < 0.01) and increased HDL-cholesterol by 13% ( p < 0.05). Combination did not show further benefit. Atorvastatin increased PCSK9 by 24% at day 1 and by 14% at week 6 ( p ≤ 0.01). Fenofibrate increased PCSK9 by 26% at week 6 ( p ≤ 0.01), but had no effect at day 1. Three weeks of combination therapy increased PCSK9 by 42%, 6 weeks by 19% ( p ≤ 0.01). PCSK9 changes were not different between treatments over 6-week periods. Conclusion Fenofibrate and Atorvastatin increased circulating PCSK9 in diabetic patients, with no additive effect after 6 weeks of combined therapy.
ISSN:	0021-9150 1879-1484