- 作者：Roeland Huijgen ; MD<sup>鈦?/sup> ; S. Matthijs Boekholdt ; MD ; PhD<sup>鈦?/sup><sup> ; sup><sup>&dagger ; sup> ; Benoit J. Arsenault ; PhD<sup>鈦?/sup> ; Weihang Bao ; PhD<sup>&Dagger ; sup> ; Jean-Michel Davaine ; MD<sup>§ ; sup> ; Fatiha Tabet ; PhD<sup>鈭?/sup> ; Francine Petrides ; BSc<sup>鈭?/sup> ; Kerry-Anne Rye ; PhD<sup>鈭?/sup><sup> ; sup><sup>¶ ; sup> ; David A. DeMicco ; PharmD<sup>&Dagger ; sup> ; Philip J. Barter ; MD ; PhD<sup>鈭?/sup><sup> ; sup><sup>¶ ; sup> ; John J.P. Kastelein ; MD ; PhD<sup>鈦?/sup> ; Gilles Lambert ; PhD<sup>§ ; sup><sup> ; sup><sup>鈭?/sup><sup> ; sup><sup>gilles.lambert@univ-nantes.frsup>
- 关键词：biomarker ; CHD ; LDL ; PCSK9 ; statin
- 刊名：Journal of the American College of Cardiology
- 出版年：2012
- 期刊代码：201_07351097
- 类别：med
- 出版时间：15 May, 2012
- 卷：59
- 期：20
- 页码：1778-1784
- 文件大小：633 K
ss="h4">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.ss="h4">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.
ss="h4">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).
ss="h4">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.
ss="h4">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]; )