Work

Joint effects of atrial fibrillation and prothrombotic genotypes on the risk of ischemic stroke

Year: 2024

Type: article

Abstract: 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.

Source: Journal of Thrombosis and Haemostasis

DOI: 10.1016/j.jtha.2024.12.022

Authors: Erin Mathiesen Hald, Maja-Lisa Løchen, Ellisiv B. Mathiesen, Kristian Hveem, Sigrid K. Brækkan, John-Bjarne Hansen