title: Plasma PCSK9 is a late biomarker of severity in patients with severe trauma injury.
abstract: BACKGROUND
  PCSK9 (proprotein convertase subtilisin kexin type 9) is a secreted protease that modulates cholesterol homeostasis by decreasing low-density lipoprotein receptor expression. Low levels of plasma lipoproteins are related to severity of illness and survival in patients of intensive care units (ICU).
  
  
  OBJECTIVE
  The aim of the study was to investigate the regulation of plasma PCSK9 and its association with plasma lipid parameters and clinical markers of severity during critical illness.
  
  
  METHODS
  The plasma biobank from the previously published HYPOLYTE prospective study was used to measure PCSK9 concentrations by ELISA at days 0 and 8 in 111 patients admitted to surgical ICU for severe multiple trauma. Patients were randomly assigned to hydrocortisone therapy or placebo.
  
  
  RESULTS
  Plasma PCSK9 levels were increased by 2-fold between days 0 and 8 (231 ± 116 vs 481 ± 227 ng/ml; P = .0001). Hydrocortisone therapy did not alter PCSK9 concentrations (451 ± 216 vs 511 ± 239 ng/ml in placebo group; P = .33). PCSK9 was positively associated with low-density lipoprotein-cholesterol (Pearson coefficient, 0.26; P = .007) at day 0, but not at day 8. At day 8, an inverse correlation was found between PCSK9 and high-density lipoprotein-cholesterol (β = -653; P = .004). Although baseline PCSK9 concentrations were not associated to severity scores, PCSK9 values at day 8 were related to injury severity score (β = 6.17; P = .0007), length of stay in ICU (β = 6.14; P = .0001), and duration of both mechanical ventilation (β = 8.26; P = .0001) and norepinephrine infusion (β = 18.57; P = .015).
  
  
  CONCLUSIONS
  Plasma PCSK9 appears as a late biomarker of illness severity in patients with severe multiple trauma.
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, University Hospital of Nantes, F-44000 Nantes, France.
authors: Maëlle
authors: M
authors: Le Bras
authors: Antoine
authors: A
authors: Roquilly
authors: Valérie
authors: V
authors: Deckert
authors: Cédric
authors: C
authors: Langhi
authors: Fanny
authors: F
authors: Feuillet
authors: Véronique
authors: V
authors: Sébille
authors: Pierre-Joachim
authors: PJ
authors: Mahé
authors: Kalyane
authors: K
authors: Bach
authors: Damien
authors: D
authors: Masson
authors: Laurent
authors: L
authors: Lagrost
authors: Philippe
authors: P
authors: Costet
authors: Karim
authors: K
authors: Asehnoune
authors: Bertrand
authors: B
authors: Cariou
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D016638:Critical Illness / Q000628:therapy; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000627:therapeutic use; D007260:Infusion Pumps; D007362:Intensive Care Units; D008297:Male; D010919:Placebos; D011379:Prognosis; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood / Q000502:physiology*; D012697:Serine Endopeptidases / Q000097:blood / Q000502:physiology*; D012720:Severity of Illness Index; D015599:Trauma Severity Indices; D014947:Wounds and Injuries / Q000097:blood / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D010919:Placebos; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D006854:Hydrocortisone