© 2009 Schattauer GmbH, Stuttgart 813 Do common prothrombotic mutations influence the risk of cerebral ischaemia in patients with patent foramen ovale? Systematic review and meta-analysis Alessandro Pezzini 1 ; Mario Grassi 2 ; Elisabetta Del Zotto 1,3 ; Alessia Giossi 1 ; Irene Volonghi 1 ; Paolo Costa 1 ; Armin Grau 4 ; Mauro Magoni 5 ; Alessandro Padovani 1 ; Christoph Lichy 6 1 Dipartimento di Scienze Mediche e Chirurgiche, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia; 2 Dipartimento di Scienze Sanitarie Applicate, Sezione di Statistica Medica e Epidemiologia, Università di Pavia, Pavia, Italia; 3 Dipartimento di Scienze Biomediche e Biotecnologie, Università degli Studi di Brescia, Brescia, Italia; 4 Department of Neurology, Städtisches Klinikum, Ludwigshafen, Germany; 5 Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Brescia, Italia; 6 Department of Neurology, University of Heidelberg, Heidelberg, Germany Summary Conflicting results are available on the association of prothrom- botic 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 (FV G1691A mutation) and the prothrombin mutation (PT G20210A 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 sub- jects. Additional unpublished data from a new series including 463 subjects were also entered into the analysis. The PT G20210A 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- Keywords Patent foramen ovale, prothrombotic disorders, young, stroke ated stroke patients (OR 2.31; 95% CI 1.20 to 4.43), whereas a trend toward an association was observed for the FV G1691A mu- tation (OR 1.18; 95% CI 0.73 to 1.90, compared to control sub- jects; OR 1.14; 95% CI 0.62 to 2.09, compared to non-PFO-as- sociated stroke patients). The status of carrier of either the FV G1691A mutation or the PT G20210A 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-as- sociated stroke patients, respectively. Addition of common pro- thrombotic genetic variants to standard initial screening may contribute to stratifying PFO-associated stroke patients at dif- ferent risk of ischaemic events and targeting secondary preven- tion strategies. Thromb Haemost 2009; 101: 813–817 Rapid and Short Communication Correspondence to: Alessandro Pezzini Clinica Neurologica Università degli Studi di Brescia P.le Spedali Civili, 1 25100 Brescia, Italia Tel.: +39 030 3995631/632, Fax: +39 030 3995027 E-mail: ale_pezzini@hotmail.com Received: November 14, 2008 Accepted after minor revision: January 11, 2009 Prepublished online: March 11, 2009 doi:10.1160/TH08-11-0747 Introduction Understanding the pathogenic basis of the relation between pat- ent foramen ovale (PFO) and cerebral ischaemia is critical when considering whether the inter-atrial cardiac defect is the cause of the vascular event, and thus, in identifying those high-risk pa- tients who may benefit from percutaneous transcatheter closure of their PFO. Recently, several reports have focused on the po- tential role of an underlying prothrombotic state in predisposing young PFO carriers to brain embolism. Screening for procoagu- lant disorders might have an impact on the stratification of risk of recurrent events in patients with stroke and PFO, and, at an indi- vidual level, might help clinicians in selecting the most appropri- ate treatment options in these cases (1, 2). However, the few studies attempting to assess the association of prothrombotic ab- normalities with PFO-related stroke have provided conflicting results (3–8), making any recommendation on whether to screen for prothrombotic disorders in these patients largely speculative. We therefore performed a systematic review and meta-analysis of the published literature regarding the association of the two For personal or educational use only. No other uses without permission. All rights reserved. Downloaded from www.thrombosis-online.com on 2018-03-23 | ID: 1001066444 | IP: 54.70.40.11