Prothrombotic Mutations as Risk Factors for Cryptogenic Ischemic Cerebrovascular Events in Young Subjects With Patent Foramen Ovale

Background and Purpose--Patent foramen ovale (PFO) has been identified as a potential risk factor for cerebrovascular ischemia. Procoagulant mutations may increase the risk and impact the choice of appropriate therapy for secondary prevention. We evaluated the prevalence of the 2 most common genetic risk factors for thromboembolism, factor V Leiden (G1691A) and prothrombin G20210A, in young PFO patients who were referred for percutaneous transcatheter closure of their PFO. Methods--Ninety-seven patients (50 men; meanSD age, 40.910.0 years) with first-ever cerebrovascular events before the age of 55 years and 160 age-matched control subjects (69 men; meanSD age, 40.410.5 years) were recruited into the study. Factor V Leiden and prothrombin G20210A mutations were detected by using a multiplex allele-specific polymerase chain reaction assay. Results--The prevalence of subjects carrying at least 1 prothrombotic genotype was significantly higher in the group of PFO patients than in the group of controls (10.3% vs 2.5%; 27.2, P0.008). Two patients (2.1%) versus 1 control subject (0.6%) and 8 cases (8.2%) versus 3 controls (1.9%) were carriers for factor V Leiden and prothrombin G20210A mutations, respectively. After adjustment for other vascular risk factors, the combination of either factor V Leiden or prothrombin G20210A and PFO was associated with a 4.7-fold (95% CI1.4 to 16.1; P0.008) increased risk of cerebral ischemia in young patients. Conclusions--Our results indicate that prothrombotic mutations are important risk factors for cerebral ischemia in young patients with PFO. Screening for thrombotic mutations should be considered in young patients with PFO-related ischemic events. (Stroke. 2007;38:2070-2073.)