Open AccessPlasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Elevated in Patients With Peripheral Artery Disease and Associated With Metabolic Disorders and Dysfunction in Circulating Progenitor Cells
Author(s) -
Chao TingHsing,
Chen IChih,
Li YiHeng,
Lee PoTseng,
Tseng ShihYa
Publication year - 2016
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.003497
Subject(s) - medicine , proprotein convertase , kexin , subtilisin , pcsk9 , progenitor cell , disease , arterial disease , peripheral , endocrinology , vascular disease , cholesterol , enzyme , lipoprotein , stem cell , biochemistry , ldl receptor , microbiology and biotechnology , chemistry , biology
Background Proprotein convertase subtilisin/kexin type 9 ( PCSK 9) is involved in cholesterol homeostasis, inflammation, and oxidative stress. This study investigated the association of plasma PCSK 9 levels with the presence and severity of peripheral artery disease ( PAD ) and with parameters of endothelial homeostasis. Methods and Results A post hoc analysis of 2 randomized trials (115 patients, 44 with PAD and 71 without atherosclerotic disease) was conducted. Patients with PAD had significantly higher plasma PCSK 9 levels than those without (471.6±29.6 versus 302.4±16.1 ng/mL, P <0.001). Parameters for glucose homeostasis, endothelial progenitor cell functions, apoptotic circulating endothelial cell counts, and plasma levels of vascular endothelial growth factor–A165 and oxidized low‐density lipoprotein were correlated with PCSK 9 concentration. By multivariable linear regression analysis, presence of PAD , plasma glucose or hemoglobin A1c levels, apoptotic circulating endothelial cell counts, and vascular endothelial growth factor–A165 concentration were found to be associated with PCSK 9 levels after multivariable adjustment. Patients with extensive involvement of PAD or with severe PAD had significantly higher PCSK 9 levels than those without PAD. Computed tomographic angiography showed that the numbers of chronic total occlusion sites and vessels involved were positively associated with PCSK 9 levels in patients with PAD ( r =0.40, P =0.01, and r =0.36, P =0.02, respectively). Conclusion PCSK 9 levels were significantly higher in patients with PAD , especially those with advanced PAD . Further large‐scale studies examining the effect of PCSK 9‐targeting therapies or the modification of PCSK 9 levels on cardiovascular outcomes in this clinical setting are warranted. Clinical Trial Registration Cohort 1: URL: ClinicalTrials.gov. Unique identifier: NCT01952756; cohort 2: URL: ClinicalTrials.gov. Unique identifier: NCT02194686.