title: Plasma 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.
abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in cholesterol homeostasis, inflammation, and oxidative stress. This study investigated the association of plasma PCSK9 levels with the presence and severity of peripheral artery disease (PAD) and with parameters of endothelial homeostasis.
  
  
  
  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 PCSK9 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 PCSK9 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 PCSK9 levels after multivariable adjustment. Patients with extensive involvement of PAD or with severe PAD had significantly higher PCSK9 levels than those without PAD. Computed tomographic angiography showed that the numbers of chronic total occlusion sites and vessels involved were positively associated with PCSK9 levels in patients with PAD (r=0.40, P=0.01, and r=0.36, P=0.02, respectively).
  
  
  
  PCSK9 levels were significantly higher in patients with PAD, especially those with advanced PAD. Further large-scale studies examining the effect of PCSK9-targeting therapies or the modification of PCSK9 levels on cardiovascular outcomes in this clinical setting are warranted.
  
  
  
  Cohort 1: URL: ClinicalTrials.gov. Unique identifier: NCT01952756; cohort 2: URL: ClinicalTrials.gov. Unique identifier: NCT02194686.
authors.affiliation: Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan chaotinghsing@gmail.com.
authors.forename: Ting-Hsing
authors.initials: TH
authors.lastname: Chao
authors.affiliation: Department of Internal Medicine, Tainan Municipal Hospital, Tainan, Taiwan.
authors.forename: I-Chih
authors.initials: IC
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan.
authors.forename: Yi-Heng
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan.
authors.forename: Po-Tseng
authors.initials: PT
authors.lastname: Lee
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Shih-Ya
authors.initials: SY
authors.lastname: Tseng
mesh_terms: D000368:Aged; D017209:Apoptosis; D001157:Arterial Occlusive Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002908:Chronic Disease; D000072226:Computed Tomography Angiography; D066026:Endothelial Progenitor Cells; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000378:metabolism; D000071449:Proprotein Convertase 9 / Q000097:blood*; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008077:Lipoproteins, LDL; D000071449:Proprotein Convertase 9; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human; C517652:hemoglobin A1c protein, human; C099252:oxidized low density lipoprotein; C472125:PCSK9 protein, human
keywords: peripheral artery disease; progenitor cell; proprotein convertase subtilisin/kexin type 9