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J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2006.101675

Inherited thrombophilia and stratification of ischemic stroke risk among oral contraceptives users

  1. Alessandro Pezzini (ale_pezzini{at}hotmail.com)
  1. Neurologia Vascolare, Spedali Civili di Brescia, Brescia, Italia, Italy
    1. Mario Grassi
    1. Sezione di Statistica Medica e Epidemiologia, Università di Pavia, Pavia, Italia, Italy
      1. Licia Iacoviello
      1. Università Cattolica del Sacro Cuore, Campobasso, Italia, Italy
        1. Elisabetta Del Zotto
        1. Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia, Italy
          1. Silvana Archetti
          1. III Laboratorio di Analisi, Biotecnologie, Università degli Studi di Brescia, Brescia, Italia, Italy
            1. Alessia Giossi
            1. Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia, Italy
              1. Alessandro Padovani
              1. Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia, Italy
                • Published Online First 10 November 2006

                Abstract

                Background and Objectives: Whether oral contraceptives (OCs) use represents a predisposing condition for arterial ischemic stroke is controversial. In particular, few data are available on what criteria should be adopted to establish an individual profile of risk before the start of OCs.

                Patients and Methods: The effect of OCs and their interaction with the G1691A polymorphisms of the factor V gene, the G20210A polymorphisms of the prothrombin gene, and the C677T polymorphisms of the MTHFR gene on the risk of cerebral ischemia were determined in a series of 108 consecutive women with ischemic stroke aged <45 years and 216 controls, in a hospital-based case-control study design.

                Results: OCs use was associated with an increased risk of cerebral ischemia (OR=3.95; 95%CI 2.29-6.78). ORs for stroke were 2.25 (95%CI 1.15-4.40), 3.94 (95%CI 2.28-6.81) and 8.87 (95%CI 3.72-21.1) for non-OCs users with the TT MTHFR genotype, OCs users without the TT MTHFR genotype and OCs users with the TT MTHFR genotype, respectively, when compared to non-OCs users without the TT MTHFR genotype, with a multiplicative independent effect. Compared with non-OCs users, ORs for stroke were 2.65 (95%CI 1.46-4.81) for OCs users with none of the studied polymorphism and 22.8 (95%CI 4.46-116.0) for OCs users with at least one of the studied polymorphisms, with a synergistic effect.

                Conclusions: Exposure to the effects of OCs may increase the risk of ischemic stroke in women with an inherited prothrombotic state. Testing for these genetic variants may allow a more accurate stratification of the population at risk before a long-term use of OCs is prescribed.

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