Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale

Background and Purpose-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 PTG20210A 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 PTG20210A variant or the FVG1691A 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 FVG1691A 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 PTG20210A variant and, to a lesser extent, the FVG1691A 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.