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

Abstract

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; meanϮSD age, 40.9Ϯ10.0 years) with first-ever cerebrovascular events before the age of 55 years and 160 age-matched control subjects (69 men; meanϮSD age, 40.4Ϯ10.5 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%; 2 ϭ7.2, Pϭ0.008). 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% CIϭ1.4 to 16.1; Pϭ0.008) 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.

Analysis of 1008 Consecutive Patients Aged 15 to 49 With First-Ever Ischemic Stroke

“…An example of well-defined potentiation is seen among women with migraine as relative stroke risk of migraine is strongly increased by oral contraceptive use and smoking. 21 PFO, with or without ASA, and its association with migraine 22 or prothrombotic mutations 23 demonstrates another complex interaction of factors with low primary risk alone. However, PFO with or without ASA, or ASA alone, should be considered as potential sources of cardioembolism in young adults-despite the difficulties of confirming the paradoxical embolism, in situ thrombosis, or transient atrial arrythmia.…”

Factor V Leiden Mutation in Reocclusion After Intra-Arterial Thrombolysis

“…5 In a relatively large study of prothrombotic gene mutations, Berge et al 6 found a small, nonsignificantly higher risk of early recurrent ischemic cerebrovascular events among patients who were carriers of the Factor V Leiden mutation. Botto et al 7 found increased prevalence of at least one prothrombotic genotype among patients with patent foramen ovale and first-ever ischemic cerebrovascular event before the age of 55 years. In fact, a combination of Factor V Leiden mutation or prothrombin gene mutation and patent foramen ovale was associated with a 4.7-fold increased risk for ischemic stroke.…”

Cardiogenic stroke in the young

“…A cumulative effect of factor V Leiden or prothrombin gene (G20210A) mutations and the presence of PFO for the occurrence of cerebral circulation disorders is emphasized. In the studies of Botto et al and Pezzini et al these mutations occurred significantly more often in patients with stroke and PFO as compared to healthy individuals [19,20]. Coagulation disorders in young patients with stroke are of minor importance, which however increases with the presence of other pathologies, such as PFO.…”