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.

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.