Matched Case-Control Study on Factor V Leiden and the Prothrombin G20210A Mutation in Patients With Ischemic Stroke/Transient Ischemic Attack Up to the Age of 60 Years

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Abstract
Background and Purpose— The role of the factor V Leiden mutation ( FVL ) and the G20210A mutation of the prothrombin ( factor II [FII] ) gene for arterial thrombosis is not clear. Methods— We investigated the prevalence of these mutations in 468 patients with an acute stroke or transient ischemic attack (TIA) before the age of 60 years and in a healthy control population individually matched for age and gender. We also analyzed interactions between the mutations, gender, standard vascular risk factors, and stroke risk. Results— The prevalence of the FVL did not differ significantly between patients and control subjects. However, we found a significant interaction between the FVL , smoking, and risk of stroke in women: female smokers without FVL had a somewhat increased risk of stroke of 2.6 (95% CI, 1.5 to 4.6; P =0.001) compared with nonsmoking noncarriers of the FVL . Stroke risk was markedly higher in female smokers who had the FVL (OR, 8.8; 95% CI, 2.0 to 38.0; P =0.004) after multivariate adjustment. No such interaction was observed in men. In contrast, the frequency of the FII G20210A mutation was significantly higher in male patients compared with controls (6% versus 1%; adjusted OR, 6.1; 95% CI, 1.3 to 28.3; P =0.021). In females, the prevalence of the mutation was 3% in both groups. We found no significant interactions of the FII G20210A mutation with other vascular risk factors and stroke risk. Conclusions— Our data indicate a highly increased risk of ischemic cerebrovascular events in women up to 60 years who smoke and have FVL . We also found evidence for an increased risk of stroke/TIA in men who have the FII G20210A mutation but not in women in this age group.