Prothrombotic mutations as risk factors for cryptogenic ischemic cerebrovascular events in young subjects with patent foramen ovale.
OBJECTIVE
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; mean+/-SD age, 40.9+/-10.0 years) with first-ever cerebrovascular events before the age of 55 years and 160 age-matched control subjects (69 men; mean+/-SD age, 40.4+/-10.5 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%; chi(2)=7.2, P=0.008). 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% CI=1.4 to 16.1; P=0.008) 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.
Botto
Nicoletta
N
CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Massa, Italy.
Spadoni
Isabella
I
Giusti
Sandra
S
Ait-Ali
Lamia
L
Sicari
Rosa
R
Andreassi
Maria Grazia
MG
D000328:Adult; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006344:Heart Septal Defects, Atrial / Q000150:complications* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000209:etiology*; D013923:Thromboembolism / Q000150:complications / Q000209:etiology / Q000235:genetics
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin