Title: Influence of 23 coronary artery disease variants on recurrent myocardial infarction or cardiac death: the GRACE Genetics Study
Authors: Wauters, Els ×
Carruthers, Kathryn F
Buysschaert, Ian
Dunbar, Donald R
Peuteman, Gilian
Belmans, Ann
Budaj, Andrzej
Van de Werf, Frans
Lambrechts, Diether
Fox, Keith A A #
Issue Date: Apr-2013
Publisher: Oxford University Press
Series Title: European heart journal vol:34 issue:13 pages:993-1001
Abstract: AimsA 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).Methods and resultsA 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).ConclusionIn 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.
ISSN: 0195-668X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Translational Genetics (Vesalius Research Center) (+)
Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat)
× corresponding author
# (joint) last author

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