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. 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.

Genetic Risk Scores Predict Recurrence of Acute Coronary Syndrome

“…The SNPs included in all these 3 GRSs are either identical to ours or represent the same gene region but with a different proxy SNP with minor exceptions. Compared with the GRSs of Tragante et al 16 , Mega et al, 17 and Labos et al, 18 our GRS with 47 SNPs comprised considerably more risk variants and accordingly covered a greater proportion of the genetic predisposition to CAD. Labos et al 18 had a slightly different focus and thus a shorter follow-up than our study, which potentially explains why the association between the GRS and the recurrent ACS could not be shown.…”

“…Compared with the GRSs of Tragante et al 16 , Mega et al, 17 and Labos et al, 18 our GRS with 47 SNPs comprised considerably more risk variants and accordingly covered a greater proportion of the genetic predisposition to CAD. Labos et al 18 had a slightly different focus and thus a shorter follow-up than our study, which potentially explains why the association between the GRS and the recurrent ACS could not be shown. The rather limited number of recurrent events in the study by Tragante et al 16 might account for the relatively weak association found in that study.…”

“…Mega et al 17 detected an association between recurrent MI and a 27-SNP GRS in patients selected for randomized controlled trial concerning statin therapy. Labos et al 18 reported a GRS, including 30 CAD SNPs, that was not associated with recurrent events within 1 year after ACS. The SNPs included in all these 3 GRSs are either identical to ours or represent the same gene region but with a different proxy SNP with minor exceptions.…”

Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute's genomic medicine portfolio

“…Several such scores have been developed based largely on alleles associated with risk of coronary disease or myocardial infarction from genome-wide association studies (GWAS), and have shown modest improvements in predicting coronary events independent of family history or cardiovascular risk factors in some studies [39,40] but not in others [41,42]. Still, such scores have been used to identify individuals at intermediate risk, where scores tend to have their greatest impact on reclassification, and to compare the effectiveness of risk reduction strategies in patients (and their clinicians) who were provided genetic risk information vs. those in whom it was withheld [43,44].…”

Predicting Prognosis in Acute Coronary Syndromes: Makeover Time for TIMI and GRACE?

“…23 On the other hand, a panel of 30 single nucleotide polymorphisms associated with an increased risk of MI, aggregated into a genetic risk score, failed to predict recurrent CV events within 1 year in 3 cohorts. 24 …”