Plasma PCSK9 Levels and Clinical Outcomes in the TNT (Treating to New Targets) Trial: A Nested Case-Control Study

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• 作者：Roeland Huijgen ; MD^?/sup> ; S. Matthijs Boekholdt ; MD ; PhD^?/sup> ; ^&dagger ; ; Benoit J. Arsenault ; PhD^?/sup> ; Weihang Bao ; PhD^&Dagger ; ; Jean-Michel Davaine ; MD^&sect ; ; Fatiha Tabet ; PhD^?/sup> ; Francine Petrides ; BSc^?/sup> ; Kerry-Anne Rye ; PhD^?/sup> ; ^¶ ; ; David A. DeMicco ; PharmD^&Dagger ; ; Philip J. Barter ; MD ; PhD^?/sup> ; ^¶ ; ; John J.P. Kastelein ; MD ; PhD^?/sup> ; Gilles Lambert ; PhD^&sect ; ; ^?/sup> ; ^{gilles.lambert@univ-nantes.fr}
• 关键词：biomarker ; CHD ; LDL ; PCSK9 ; statin
• 刊名：Journal of the American College of Cardiology
• 出版年：2012
• 出版时间：15 May, 2012
• 年：2012
• 卷：59
• 期：20
• 页码：1778-1784
• 全文大小：633 K

文摘

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Objectives

The purpose of this study was to investigate whether high levels of circulating proprotein convertase subtilisin kexin type 9 (PCSK9) would increase cardiovascular risk in statin-treated patients.

Background

Statins activate low-density lipoprotein (LDL) receptor gene expression, thus lowering plasma LDL levels. But statins also activate the expression of PCSK9, a secreted inhibitor of the LDL receptor, thereby limiting their beneficial effects.

Methods

We have measured the plasma PCSK9 levels of 1,613 patients with stable coronary heart disease enrolled in the Treating to New Targets study, a randomized trial that compared the efficacy of high- versus low-dose atorvastatin. After a run-in period with atorvastatin 10 mg daily, patients were randomized to either continue with 10 mg or be up-titrated to 80 mg of atorvastatin, and followed during 5 years for major cardiovascular events (MCVEs).

Results

Circulating PCSK9 levels measured at randomization were predictive of clinical outcomes in the group randomized to remain on atorvastatin 10 mg (p = 0.039), but not in the group that intensified atorvastatin treatment to 80 mg (p = 0.24). Further, PCSK9 levels measured 1 year post-randomization did not change upon increase of the statin dose.

Conclusions

PCSK9 levels predict cardiovascular events in patients treated with low-dose atorvastatin. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; )