Key result
In patients with atrial fibrillation, having ≥1 risk allele in the ABO gene was associated with a 1.4-fold increased risk of ischemic stroke compared to having no risk allele (HR 1.42; 95% CI 0.99-2.04).
Why the study?
Whether prothrombotic single nucleotide polymorphisms impact ischemic stroke risk in atrial fibrillation is not well known.
Do prothrombotic SNPs increase the risk of ischemic stroke in patients with atrial fibrillation?
Cohort (n=14,583)
Yes
Do prothrombotic SNPs increase the risk of ischemic stroke in patients with atrial fibrillation?
Hazard Ratio: 1.42 (95% CI 0.99–2.04)
Most prothrombotic SNPs are not associated with excess ischemic stroke risk in patients with atrial fibrillation, though the ABO SNP may confer a modestly increased risk.
Non-O blood type may modestly raise stroke risk in AF; leaves open whether genetic testing refines stratification beyond clinical scores.
BACKGROUND: Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Whether prothrombotic single nucleotide polymorphisms (SNPs) impact stroke risk in AF is not well known. OBJECTIVES: To investigate the joint effects of 5 prothrombotic SNPs and AF on ischemic stroke risk. METHODS: A subcohort (n = 14 583) was randomly sampled from the Tromsø (1994-2012) and the Trøndelag Health (1995-2008) studies. DNA was genotyped for rs8176719 (ABO blood type), rs6025 (factor [F]V Leiden), rs1799963 (prothrombin G20210A), rs2066865 (fibrinogen-γ), and rs2036914 (F11). Hazard ratios (HRs) with 95% CIs for incident ischemic stroke were estimated by AF status for individual SNPs and by categories of a genetic risk score. RESULTS: A total of 1091 participants developed AF during follow-up, of whom 169 (15.5%) subsequently had a stroke. Having ≥1 risk allele in prothrombin, FV Leiden, F11, or fibrinogen-γ was not associated with excess stroke risk in AF. In the absence of AF, ≥1 risk allele(s) in ABO was not associated with stroke (HR, 1.03; 95% CI, 0.85-1.25), whereas those with AF and ≥1 risk allele(s) in ABO had a 1.4-fold increased stroke risk compared with those with AF and no risk allele (HR, 1.42; 95% CI, 0.99-2.04). There was no linear increase in stroke risk across categories of the genetic risk score in participants either with or without AF. CONCLUSION: Most prothrombotic SNPs were not associated with ischemic stroke risk, regardless of AF status. The ABO SNP was associated with ischemic stroke risk in those with AF only.
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Hald et al. (2024) conducted a cohort in Atrial fibrillation and ischemic stroke (n=14,583). Prothrombotic single nucleotide polymorphisms (SNPs) vs. Absence of risk alleles was evaluated on incident ischemic stroke (HR 1.42, 95% CI 0.99-2.04). In patients with atrial fibrillation, having ≥1 risk allele in the ABO gene was associated with a 1.4-fold increased risk of ischemic stroke compared to having no risk allele (HR 1.42; 95% CI 0.99-2.04).
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