title: Utility of a genetic risk score to predict recurrent cardiovascular events 1 year after an acute coronary syndrome: A pooled analysis of the RISCA, PRAXY, and TRIUMPH cohorts.
abstract: BACKGROUND
  Limited evidence exists regarding the utility of genetic risk scores (GRS) in predicting recurrent cardiovascular events after acute coronary syndrome (ACS). We sought to determine whether a GRS would predict early recurrent cardiovascular events within 1 year of ACS.
  
  
  RESULTS
  Participants admitted with acute coronary syndromes from the RISCA, PRAXY, and TRIUMPH cohorts, were genotyped for 30 single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) or myocardial infarction (MI) in prior genome wide association studies. A 30 SNP CAD/MI GRS was constructed. The primary endpoint was defined as all-cause mortality, recurrent ACS or cardiac re-hospitalization within 1 year of ACS admission. Results across all cohorts for the 30 SNP CAD/MI GRS were pooled using a random-effects model. There were 1040 patients from the RISCA cohort, 691 patients from the PRAXY cohort, and 1772 patients from the TRIUMPH cohort included in the analysis and 389 occurrences of the primary endpoint of recurrent events at 1-year post-ACS. In unadjusted and fully adjusted analyses, a 30 SNP GRS was not significantly associated with recurrent events (HR per allele 0.97 (95%CI 0.91-1.03) for RISCA, HR 0.99 (95%CI 0.93-1.05) for PRAXY, 0.98 (95%CI 0.94-1.02) for TRIUMPH, and 0.98 (95%CI 0.95-1.01) for the pooled analysis). Addition of this GRS to the GRACE risk model did not significantly improve risk prediction.
  
  
  CONCLUSIONS
  The 30 MI SNP GRS was not associated with recurrent events 1-year post ACS in pooled analyses across cohorts and did not improve risk discrimination or reclassification indices. Our results suggest that the genetic etiology of early events post-ACS may differ from later events.
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Labos
authors.affiliation: Department of Medicine, Washington University, St. Louis, MO, USA.
authors.forename: Sara C
authors.initials: SC
authors.lastname: Martinez
authors.affiliation: Department of Biochemistry, McGill University, Montreal, QC, Canada.
authors.forename: Rui Hao
authors.initials: RH
authors.lastname: Leo Wang
authors.affiliation: Department of Genetics, Washington University, St. Louis, MO, USA.
authors.forename: Petra A
authors.initials: PA
authors.lastname: Lenzini
authors.affiliation: Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Pilote
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie, Laval University, Quebec City, QC, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Bogaty
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: James M
authors.initials: JM
authors.lastname: Brophy
authors.affiliation: Department of Medicine, McGill University, Montreal, QC, Canada; Department of Human Genetics, McGill University, Montreal, QC, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
authors.affiliation: Department of Medicine, Washington University, St. Louis, MO, USA; Department of Genetics, Washington University, St. Louis, MO, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Cresci
authors.affiliation: Department of Medicine, McGill University, Montreal, QC, Canada. Electronic address: george.thanassoulis@mcgill.ca.
authors.forename: George
authors.initials: G
authors.lastname: Thanassoulis
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D000368:Aged; D002986:Clinical Trials as Topic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010359:Patient Readmission; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D005819:Genetic Markers
keywords: Acute coronary syndrome; Genetic risk score; Risk prediction