title: Prognostic value of PCSK9 levels in patients with acute coronary syndromes.
abstract: OBJECTIVE
  Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS).
  
  
  RESULTS
  Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99).
  
  
  CONCLUSIONS
  In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.
authors.affiliation: Cardiology Division, Geneva University Hospitals, Rue Gabrielle-Perret Gentil 4, Geneva 14 1211, Switzerland baris.gencer@hcuge.ch.
authors.forename: Baris
authors.initials: B
authors.lastname: Gencer
authors.affiliation: Cardiology Division, Geneva University Hospitals, Rue Gabrielle-Perret Gentil 4, Geneva 14 1211, Switzerland First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine and IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, 6 viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
authors.affiliation: Department of Ambulatory Care and Community Medicine, Lausanne University, Lausanne, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Nanchen
authors.affiliation: Cardiology Division, Geneva University Hospitals, Rue Gabrielle-Perret Gentil 4, Geneva 14 1211, Switzerland First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine and IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, 6 viale Benedetto XV, 16132 Genoa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Carbone
authors.affiliation: Department of Cardiology, University Heart Center, University of Zurich, Zurich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Klingenberg
authors.affiliation: Laboratory Medicine Division, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
authors.affiliation: Institute of Social and Preventive Medicine, Clinical Trials Unit, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Soheila
authors.initials: S
authors.lastname: Aghlmandi
authors.affiliation: Institute of Social and Preventive Medicine, Clinical Trials Unit, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Dik
authors.initials: D
authors.lastname: Heg
authors.affiliation: Department of Cardiology, University Hospital of Bern, Bern, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Räber
authors.affiliation: Department of Ambulatory Care and Community Medicine, Lausanne University, Lausanne, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Auer
authors.affiliation: Institute of Primary Health Care, University of Bern, Bern, Switzerland Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St Michael's Hospital, University of Toronto, Toronto, ON M5S, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Jüni
authors.affiliation: Department of Cardiology, University Hospital of Bern, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.affiliation: Department of Cardiology, University Heart Center, University of Zurich, Zurich, Switzerland.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.affiliation: Department of Cardiology, University Heart Center, University of Zurich, Zurich, Switzerland.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Matter
authors.affiliation: Department of General Internal Medicine, University Hospital of Bern, Bern, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
authors.affiliation: Cardiology Division, Geneva University Hospitals, Rue Gabrielle-Perret Gentil 4, Geneva 14 1211, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Mach
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000097:blood*; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Acute coronary syndromes; Cohort studies; Familial hypercholesterolaemia; Lipids; PCSK9