Journal
ATHEROSCLEROSIS
Volume 242, Issue 1, Pages 261-267Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2015.07.029
Keywords
Genetic risk score; Acute coronary syndrome; Risk prediction
Funding
- Fonds de la Recherche en Sante du Quebec (FRQS) Chercheur Boursier Clinicien Salary Award [FRQS-24958]
- CIHR grant [CIHR MOP-119380, CIHR IGO-86113]
- FRSQ
- Heart and Stroke Foundation of Canada
- Merck Frosst Canada
- Pfizer Canada
- National Institutes of Health [R01 NR013396]
- Canadian Institutes of Health Research
- Heart and Stroke Foundations of Quebec
- Nova Scotia
- Alberta
- Ontario
- Yukon
- British Columbia [MOP-89369]
- National Institutes of Health: Washington University School of Medicine SCCOR [P50 HL077113]
- NCI Cancer Center Support Grant [P30 CA91842]
- ICTS/CTSA Grant [UL1TR000448]
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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. Methods & 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. Conclusion: 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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