title: Plasma PCSK9 levels are elevated with acute myocardial infarction in two independent retrospective angiographic studies.
abstract: OBJECTIVE
  Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein (LDL) receptor. Mutations that block PCSK9 secretion reduce LDL-cholesterol and the incidence of myocardial infarction (MI). However, it remains unclear whether elevated plasma PCSK9 associates with coronary atherosclerosis (CAD) or more directly with rupture of the plaque causing MI.
  
  
  RESULTS
  Plasma PCSK9 was measured by ELISA in 645 angiographically defined controls (<30% coronary stenosis) and 3,273 cases of CAD (>50% stenosis in a major coronary artery) from the Ottawa Heart Genomics Study. Because lipid lowering medications elevated plasma PCSK9, confounding association with disease, only individuals not taking a lipid lowering medication were considered (279 controls and 492 with CAD). Replication was sought in 357 controls and 465 with CAD from the Emory Cardiology Biobank study. PCSK9 levels were not associated with CAD in Ottawa, but were elevated with CAD in Emory. Plasma PCSK9 levels were elevated in 45 cases with acute MI (363.5±140.0 ng/ml) compared to 398 CAD cases without MI (302.0±91.3 ng/ml, p = 0.004) in Ottawa. This finding was replicated in the Emory study in 74 cases of acute MI (445.0±171.7 ng/ml) compared to 273 CAD cases without MI (369.9±139.1 ng/ml, p = 3.7×10(-4)). Since PCSK9 levels were similar in CAD patients with or without a prior (non-acute) MI, our finding suggests that plasma PCSK9 is elevated either immediately prior to or at the time of MI.
  
  
  CONCLUSIONS
  Plasma PCSK9 levels are increased with acute MI.
authors.affiliation: Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Center for Genetics and Inherited Diseases, Taibah University, Almadina, Saudi Arabia.
authors.forename: Naif A M
authors.initials: NA
authors.lastname: Almontashiri
authors.affiliation: Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Ragnar O
authors.initials: RO
authors.lastname: Vilmundarson
authors.affiliation: Department of Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Nima
authors.initials: N
authors.lastname: Ghasemzadeh
authors.affiliation: Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Sonny
authors.initials: S
authors.lastname: Dandona
authors.affiliation: Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Roberts
authors.affiliation: Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.affiliation: Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Hsiao-Huei
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Alexandre F R
authors.initials: AF
authors.lastname: Stewart
mesh_terms: D018070:Biological Specimen Banks; D002170:Canada; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood; D005260:Female; D023281:Genomics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000097:blood*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases