Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention.
Aged
Aged, 80 and over
Aspirin
/ administration & dosage
Clinical Trials as Topic
Clopidogrel
/ administration & dosage
Coronary Artery Disease
/ enzymology
Coronary Restenosis
/ enzymology
Coronary Thrombosis
/ enzymology
Drug Resistance
/ genetics
Europe
Female
Genetic Association Studies
Genetic Predisposition to Disease
Hemorrhage
/ chemically induced
Homozygote
Humans
Male
Middle Aged
Percutaneous Coronary Intervention
/ adverse effects
Platelet Aggregation Inhibitors
/ administration & dosage
Polymorphism, Single Nucleotide
Registries
Retrospective Studies
Risk Assessment
Risk Factors
Soluble Guanylyl Cyclase
/ genetics
Stents
Time Factors
Treatment Outcome
Genetic variation
Genome-wide association studies
On-aspirin platelet reactivity
Platelet aggregation
Stent thrombosis
Journal
Cardiovascular research
ISSN: 1755-3245
Titre abrégé: Cardiovasc Res
Pays: England
ID NLM: 0077427
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
received:
10
08
2018
revised:
19
12
2018
accepted:
16
01
2019
pubmed:
16
2
2019
medline:
23
6
2020
entrez:
16
2
2019
Statut:
ppublish
Résumé
A common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention. The association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91-209) vs. 134 (85-194) AU⋅min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203 AU⋅min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08-2.68; P = 0.02). Bleeding risk was not altered. We conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.
Identifiants
pubmed: 30768153
pii: 5320311
doi: 10.1093/cvr/cvz015
doi:
Substances chimiques
GUCY1A1 protein, human
0
Platelet Aggregation Inhibitors
0
Clopidogrel
A74586SNO7
Soluble Guanylyl Cyclase
EC 4.6.1.2
Aspirin
R16CO5Y76E
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1512-1518Commentaires et corrections
Type : CommentIn
Informations de copyright
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.