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

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.