title: Influence of 23 coronary artery disease variants on recurrent myocardial infarction or cardiac death: the GRACE Genetics Study.
abstract: OBJECTIVE
  A pooled analysis of 14 genome-wide association studies revealed 23 susceptibility loci for coronary artery disease (CAD), thereby providing the most comprehensive genetic blueprint of CAD susceptibility. Here, we evaluated whether these 23 loci also predispose to recurrent myocardial infarction (MI) or cardiac death following an acute coronary syndrome (ACS).
  
  
  RESULTS
  A total of 2099 ACS patients enrolled in the Global Registry of Acute Coronary Events (GRACE) UK-Belgian study were prospectively followed for a median of 5 years (1668 days). C-allele carriers of the rs579459 variant, which is located upstream of the ABO gene and correlates with blood group A, were independently associated with recurrent MI [multivariable-adjusted hazard ratio (HR) 2.25, CI = 1.37-3.71; P = 0.001] and with recurrent MI or cardiac death [multivariable-adjusted (HR) 1.80, CI = 1.09-2.95; P = 0.021] within 5 years after an index ACS. The association of rs579459 was replicated in 1250 Polish patients with 6 months follow-up after an index ACS [multivariable-adjusted (HR) 2.70, CI = 1.26-5.82; P = 0.011 for recurrent MI]. Addition of rs579459 to a prediction model of 17 clinical risk factors improved risk classification for recurrent MI or cardiac death at 6 months as calculated by the integrated discrimination improvement method (P = 0.037), but not by C-statistics (P = 0.096).
  
  
  CONCLUSIONS
  In this observational study, rs579459 was independently associated with adverse cardiac outcome after ACS. A weak improvement in clinical risk prediction was also observed, suggesting that rs579459 should be further tested as a potentially relevant contributor to risk prediction models for adverse outcome following ACS.
authors.affiliation: Vesalius Research Center (VRC), VIB and KU Leuven, Campus Gasthuisberg, Herestraat 49, Box 912, B-3000 Leuven, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Wauters
authors.forename: Kathryn F
authors.initials: KF
authors.lastname: Carruthers
authors.forename: Ian
authors.initials: I
authors.lastname: Buysschaert
authors.forename: Donald R
authors.initials: DR
authors.lastname: Dunbar
authors.forename: Gilian
authors.initials: G
authors.lastname: Peuteman
authors.forename: Ann
authors.initials: A
authors.lastname: Belmans
authors.forename: Andrzej
authors.initials: A
authors.lastname: Budaj
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics; D000368:Aged; D001530:Belgium / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000235:genetics* / Q000401:mortality; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000401:mortality; D010641:Phenotype; D011044:Poland / Q000453:epidemiology; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D012042:Registries; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000017:ABO Blood-Group System