PAPER

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

A Pezzini¹, M Grassi², L Iacoviello³, E Del Zotto⁴, S Archetti⁵, A Giossi⁴, A Padovani⁴

¹ Dipartimento di Scienze Mediche e Chirurgiche, Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, Brescia, Italy
² Dipartimento di Scienze Sanitarie Applicate, Sezione di Statistica Medica e Epidemiologia, Università di Pavia, Pavia, Italy
³ Centro di Ricerca e Formazione ad Alta Tecnologia nelle Scienze Biomediche, Università Cattolica del Sacro Cuore, Campobasso, Italy
⁴ Dipartimento di Scienze Mediche e Chirurgiche, Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italy
⁵ III Laboratorio di Analisi, Biotecnologie, Università degli Studi di Brescia, Brescia, Italy

Correspondence to:
Dr A Pezzini
Stroke Unit, Neurologia Vascolare, Spedali Civili di Brescia, P.le Spedali Civili, 1, 25100 Brescia, Italy;ale_pezzini{at}hotmail.com

Background: Whether use of oral contraceptives is a risk factor for arterial ischaemic 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 oral contraceptives.

Patients and methods: The effects of oral contraceptives 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 ischaemia were determined in a series of 108 consecutive women aged <45 years with ischaemic stroke and 216 controls, in a hospital-based case–control study design.

Results: Use of oral contraceptives was associated with an increased risk of cerebral ischaemia (odds ratio (OR) 3.95; 95% confidence interval (CI) 2.29 to 6.78). ORs for stroke were 2.25 (95% CI 1.15 to 4.40), 3.94 (95% CI 2.28 to 6.81) and 8.87 (95% CI 3.72 to 21.1) for non-oral contraceptive users with the TT MTHFR genotype, oral contraceptive users without the TT MTHFR genotype and oral contraceptive users with the TT MTHFR genotype, respectively, when compared with non-oral contraceptive users without the TT MTHFR genotype, with a multiplicative independent effect. Compared with non-oral contraceptive users, ORs for stroke were 2.65 (95% CI 1.46 to 4.81) for oral contraceptive users with none of the studied polymorphisms and 22.8 (95% CI 4.46 to 116.00) for oral contraceptive users with at least one of the studied polymorphisms, with a synergistic effect.

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

Abbreviations: AIC, Akaike’s information criterion; BIC, Bayesian information criterion

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