Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale.
OBJECTIVE
The pathogenic link between patent foramen ovale (PFO) and stroke remains unknown in most cases. We investigated the association between inherited thrombophilic disorders and PFO-related strokes in a series of young adults in the setting of a case-control study.


METHODS
We investigated 125 consecutive subjects (age, 34.7+/-7.3 years) with ischemic stroke and 149 age- and sex-matched control subjects. PFO was assessed in all patients with transcranial Doppler sonography with intravenous injection of agitated saline according to a standardized protocol. Genetic analyses for the factor V (FV)(G1691A) mutation, the prothrombin (PT)(G20210A) variant, and the TT677 genotype of methylenetetrahydrofolate reductase (MTHFR) were performed in all subjects.


RESULTS
A pathogenic role of PFO was presumed in 36 patients (PFO+). Interatrial right-to-left shunt either was not detected or was considered unrelated to stroke occurrence in the remaining 89 patients (PFO-). The PT(G20210A) variant was more frequent in the PFO+ group compared with control subjects and the PFO- group (PFO+ versus control subjects, 11% versus 2%; 95% CI, 0.04 to 0.94; PFO+ versus PFO-, 11% versus 1.1%; 95% CI, 1.09 to 109; P=0.047). A similar distribution was observed for subjects carrying either the PT(G20210A) variant or the FV(G1691A) mutation (PFO+ versus control subjects, 19.4% versus 5.3%; 95% CI, 0.08 to 0.75; PFO+ versus PFO-, 19.4% versus 3.3%; 95% CI, 1.45 to 26.1; P=0.021). Combined thrombophilic defects were observed in 3 subjects of the PFO+ group, in 2 control subjects (8.3% versus 1.3%; 95% CI, 0.01 to 0.66; P=0.015), and in 0 subjects in the PFO- group. A trend toward a difference in the frequency of the FV(G1691A) mutation between PFO+ and control subjects was found after bivariate analysis (11% versus 3.3%; P=0.068) but not after multinomial logistic regression analysis. No significant association was found in the distribution of the TT MTHFR genotype in the 3 groups.


CONCLUSIONS
In young adults, the PT(G20210A) variant and, to a lesser extent, the FV(G1691A) mutation may represent risk factors for PFO-related cerebral infarcts. A role of systemic thrombophilic disorders in the pathogenesis of this specific subtype of stroke may be hypothesized.
Pezzini
Alessandro
A
Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia. ale_pezzini@hotmail.com
Del Zotto
Elisabetta
E
Magoni
Mauro
M
Costa
Angelo
A
Archetti
Silvana
S
Grassi
Mario
M
Akkawi
Nabil Maalikjy
NM
Albertini
Alberto
A
Assanelli
Deodato
D
Vignolo
Luigi Amedeo
LA
Padovani
Alessandro
A
D000328:Adult; D002545:Brain Ischemia / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000235:genetics; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006344:Heart Septal Defects, Atrial / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011446:Prospective Studies; D011516:Prothrombin / Q000235:genetics; D020521:Stroke / Q000175:diagnosis / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics
D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)