Do common prothrombotic mutations influence the risk of cerebral ischaemia in patients with patent foramen ovale?

Summary

Conflicting results are available on the association of prothrombotic genetic abnormalities with patent foramen ovale (PFO)-related cerebral ischaemia. We comprehensively sought and identified studies of the association of both the factor V Leiden (FVG1691A mutation) and the prothrombin mutation (PTG20210A mutation) with PFO-related cerebral ischaemia and did meta-analyses to assess the evidence for such a relation. We analysed data from six eligible studies in 856 cases and 1,001 control subjects. Additional unpublished data from a new series including 463 subjects were also entered into the analysis. The PTG20210A variant was significantly associated with PFO-related stroke in comparison with both control subjects (odds ratio [OR] 3.85; 95% confidence interval [CI] 2.22 to 6.66) and non-PFO-associ ated stroke patients (OR 2.31; 95% CI 1.20 to 4.43), whereas a trend toward an association was observed for the FVG1691A mutation (OR 1.18; 95% CI 0.73 to 1.90, compared to control subjects; OR 1.14; 95% CI 0.62 to 2.09, compared to non-PFO-associated stroke patients). The status of carrier of either the FVG1691A mutation or the PTG20210A variant was associated with a risk for stroke of 1.98 (95% CI 1.38 to 2.83) and 1.62 (95% CI 1.03 to 2.57), as compared to control subjects and non-PFO-associated stroke patients, respectively. Addition of common prothrombotic genetic variants to standard initial screening may contribute to stratifying PFO-associated stroke patients at different risk of ischaemic events and targeting secondary prevention strategies.

Keywords

Patent foramen ovale - prothrombotic disorders - young - stroke

• References

• 1 Thaler DA, Saver JL. Cryptogenic stroke and patent foramen ovale. Curr Opin Cardiol 2008; 23: 537-544.
• 2 Saver JL. Cryptogenic stroke in patients with patent foramen ovale. Curr Atheroscler Rep 2007; 09: 319-325.
• 3 Pezzini A, Del Zotto E, Magoni M. et al. Inherited thrombophilic disorders in young adults with ischaemic stroke and patent foramen ovale. Stroke 2003; 34: 28-33.
• 4 Lichy C, Reuner KH, Buggle F. et al. Prothrombin G20210A mutation, but not factor V Leiden, is a risk factor in patients with persistent foramen ovale and otherwise unexplained cerebral ischaemia. Cerebrovasc Dis 2003; 16: 83-87.
• 5 Belvis R, Santamaria A, Marti-Fabregas J. et al. Patent foramen ovale and prothrombotic markers in young stroke patients. Blood Coagul Fibrinolysis 2007; 18: 537-542.
• 6 Offelli P, Zanchetta M, Pedon L. et al. Thrombophilia in young patients with cryptogenic stroke and patent foramen ovale (PFO). Thromb Haemost 2007; 98: 906-907.
• 7 Karttunen V, Hiltunen L, Rasi V. et al. Factor V Leiden and prothrombin gene mutation may predispose to paradoxical embolism in subjects with patent for-amen ovale. Blood Coagul Fibrinolysis 2003; 14: 261-268.
• 8 Botto N, Spadoni I, Giusti S. et al. Prothrombotic mutations as risk factors for cryptogenic ischaemic cerebrovascular events in young subjects with patent for-amen ovale. Stroke 2007; 38: 2070-2073.
• 9 Silver MD, Dorsey GS. Aneurysms of the septum primum in adults. Arch Pathol Lab Med 1978; 102: 62-65.
• 10 Schneider B, Hanrath P, Vogel P. et al. Improved morphologic characterization of atrial septal aneurysm by transesophageal echocardiography: relation to cerebrovascular events. J Am Coll Cardiol 1990; 16: 1000-1009.
• 11 Berthet K, Lavergne T, Cohen A. et al. Significant association of atrial vulnerability with atrial septal abnormalities in young patients with ischaemic stroke of unknown cause. Stroke 2000; 31: 398-403.
• 12 Martinelli I, Battaglioli T, Razzari C. et al. Type and location of venous thromboembolism in patients with factor V Leiden or prothrombin G20210A and in those with no thrombophilia. J Thromb Haemost 2007; 05: 98-101.
• 13 Egger M, Davey Smith G. Meta-analysis. Bias in location and selection of studies. Br Med J 1998; 316: 61-66.