title: Plasma Proprotein Convertase Subtilisin Kexin Type 9 as a Predictor of Carotid Atherosclerosis in Asymptomatic Adults.
abstract: BACKGROUND
  Atherosclerosis is a lipid-driven inflammatory disease of the arterial wall involving complex and multifactorial processes. Proprotein convertase subtilisin kexin type 9 (PCSK9) may play a role in the development of atherosclerosis.
  
  
  METHODS
  We investigated the associations between serum PCSK9 and carotid intima-medial wall thickness (IMT), a measure of subclinical atherosclerosis that predicts cardiovascular events, in 295 asymptomatic subjects from community. Carotid IMT was determined by high-resolution B-mode carotid ultrasonography and serum PCSK9 was measured by immunoassay.
  
  
  RESULTS
  In univariate analysis, serum PCSK9 concentration was positively (P<0.05 in all) associated with age (r=0.204), BMI (r=0.149), waist circumference (r=0.139), systolic blood pressures (r=0.116), glucose (r=0.211), insulin (r=0.178), HOMA score (r=0.195), plasma triglyceride (r=0.285), total cholesterol (r=0.241) and LDL-cholesterol concentrations (r=0.172). In multivariate regression including male gender, hypertension, smoking status, HOMA score, obesity, LDL-cholesterol, lipoprotein (a) or markers of inflammation, serum PCSK9 remained an independent predictor of mean carotid IMT (P<0.001).
  
  
  CONCLUSIONS
  These data suggest that serum levels of PCSK9 may contribute to increased risk of subclinical carotid atherosclerosis independent of conventional risk factors. Whether PCSK9 inhibition improves cardiovascular outcomes remains to be demonstrated in large, ongoing clinical trials.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. Electronic address: dick.chan@uwa.edu.au.
authors.forename: Dick C
authors.initials: DC
authors.lastname: Chan
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
authors.forename: B M
authors.initials: BM
authors.lastname: McQuillan
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hung
authors.affiliation: PathWest Laboratory Medicine, QEII, Perth, WA and Pathology and Laboratory Medicine, University of Western Australia, Perth, WA.
authors.forename: John P
authors.initials: JP
authors.lastname: Beilby
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, WA, Australia.
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000328:Adult; D000368:Aged; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D000071449:Proprotein Convertase 9 / Q000097:blood*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Carotid IMT and Cardiovascular disease; PCSK9