title: Association of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) With Cardiovascular Risk in Primary Prevention.
abstract: OBJECTIVE
  Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the modulation of low-density lipoprotein metabolism. This study was conducted to evaluate the relationship between serum PCSK9 concentrations and measures of vascular health, subclinical atherosclerosis, and adverse cardiovascular events. The relationship between traditional risk factors and PCSK9 concentrations was also examined.
  
  
  RESULTS
  The cohort consisted of 1527 middle-aged men enrolled in the Firefighters and Their Endothelium (FATE) study, who were free of vascular disease and followed up over a mean period of 7.2±1.7 years. Baseline evaluation included assessment of traditional cardiovascular risk factors and measurements of flow-mediated dilation, reactive hyperemic velocity time integral, and carotid intima-media thickness. Biochemical parameters, including serum PCSK9 concentrations, were analyzed to determine predictors of vascular measures and to evaluate the role of PCSK9 in the occurrence of adverse cardiovascular events. Multivariate linear regression analyses indicated that body mass index, insulin, low-density lipoprotein-cholesterol, and triglycerides were independent predictors of PCSK9. Further modeling revealed no correlation between PCSK9 concentration and carotid intima media thickness, flow-mediated dilation, or reactive hyperemic velocity time integral. Analyses indicated no significant association between PCSK9 concentrations and cardiovascular event occurrences.
  
  
  CONCLUSIONS
  Although correlated with low-density lipoprotein-cholesterol, insulin, and triglycerides, PCSK9 was not associated with measures of vascular function or structure. There was also no significant relationship between PCSK9 concentrations and cardiovascular events. Thus, although PCSK9 is an important therapeutic target to reduce circulating low-density lipoprotein-cholesterol concentrations, it is unlikely to be a biomarker of atherosclerotic risk or vascular health.
authors: From the Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (Y.M.Z., T.J.A., K.S., M.F.); Department of Laboratory Medicine (M.J.M.), Population Health Research Institute (M.J.M., E.M.L.) and Department of Medicine (E.M.L.), McMaster University Hamilton, Hamilton, Ontario, Canada (E.M.L.); and Department of Surgery, Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (S.V.).
authors: Yiming M
authors: YM
authors: Zhu
authors: From the Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (Y.M.Z., T.J.A., K.S., M.F.); Department of Laboratory Medicine (M.J.M.), Population Health Research Institute (M.J.M., E.M.L.) and Department of Medicine (E.M.L.), McMaster University Hamilton, Hamilton, Ontario, Canada (E.M.L.); and Department of Surgery, Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (S.V.). todd.anderson@albertahealthservices.ca.
authors: Todd J
authors: TJ
authors: Anderson
authors: From the Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (Y.M.Z., T.J.A., K.S., M.F.); Department of Laboratory Medicine (M.J.M.), Population Health Research Institute (M.J.M., E.M.L.) and Department of Medicine (E.M.L.), McMaster University Hamilton, Hamilton, Ontario, Canada (E.M.L.); and Department of Surgery, Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (S.V.).
authors: Khokan
authors: K
authors: Sikdar
authors: From the Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (Y.M.Z., T.J.A., K.S., M.F.); Department of Laboratory Medicine (M.J.M.), Population Health Research Institute (M.J.M., E.M.L.) and Department of Medicine (E.M.L.), McMaster University Hamilton, Hamilton, Ontario, Canada (E.M.L.); and Department of Surgery, Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (S.V.).
authors: Marinda
authors: M
authors: Fung
authors: From the Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (Y.M.Z., T.J.A., K.S., M.F.); Department of Laboratory Medicine (M.J.M.), Population Health Research Institute (M.J.M., E.M.L.) and Department of Medicine (E.M.L.), McMaster University Hamilton, Hamilton, Ontario, Canada (E.M.L.); and Department of Surgery, Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (S.V.).
authors: Matthew J
authors: MJ
authors: McQueen
authors: From the Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (Y.M.Z., T.J.A., K.S., M.F.); Department of Laboratory Medicine (M.J.M.), Population Health Research Institute (M.J.M., E.M.L.) and Department of Medicine (E.M.L.), McMaster University Hamilton, Hamilton, Ontario, Canada (E.M.L.); and Department of Surgery, Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (S.V.).
authors: Eva M
authors: EM
authors: Lonn
authors: From the Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (Y.M.Z., T.J.A., K.S., M.F.); Department of Laboratory Medicine (M.J.M.), Population Health Research Institute (M.J.M., E.M.L.) and Department of Medicine (E.M.L.), McMaster University Hamilton, Hamilton, Ontario, Canada (E.M.L.); and Department of Surgery, Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (S.V.).
authors: Subodh
authors: S
authors: Verma
mesh_terms: D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality / Q000517:prevention & control*; D059168:Carotid Intima-Media Thickness; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011322:Primary Prevention / Q000379:methods; D011379:Prognosis; D016016:Proportional Hazards Models; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000097:blood*; D012720:Severity of Illness Index; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: LDL cholesterol; PCSK9 protein; atherosclerosis; body mass index; cardiovascular diseases; human