title: Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke.
abstract: BACKGROUND
  The role of inherited prothrombotic conditions, including factor V Leiden (FV G1691A), prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T genotype, in the pathogenesis of ischemic stroke is not well established. The effects of these factors may be potentiated by the use of oral contraceptives, analogous to observations in venous thrombosis.
  
  
  METHODS
  Patients (n = 193) were women aged 20-49 years with ischemic stroke. Controls (n = 767) were women without arterial thrombosis stratified for age, calendar year of the index event, and residence. The relative risk of ischemic stroke was estimated with unconditional logistic regression, adjusted for stratification variables.
  
  
  RESULTS
  Factor V Leiden and MTHFR 677TT were more common in patients than in controls [odds ratio (OR): 1.8; 95% confidence interval (CI): 0.9-3.6 respectively OR: 1.5; 95% CI: 0.9-2.6]. The frequency of prothrombin G20210A was similar in cases and controls. Carriers of FV Leiden using oral contraceptives had a 11.2-fold (95% CI: 4.3-29.0) higher risk of ischemic stroke than women without either risk factor. Women with MTHFR 677TT using oral contraceptives had a 5.4-fold (95% CI: 2.4-12.0) higher risk than women without these risk factors.
  
  
  CONCLUSIONS
  These data suggest that carriers of FV Leiden or MTHFR 677TT who use oral contraceptives have an increased risk of ischemic stroke. When these findings are confirmed, a cost-effectiveness analysis should indicate whether ischemic stroke could be prevented with genetic testing before the start of oral contraceptives.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, The Netherlands.
authors.forename: A J C
authors.initials: AJ
authors.lastname: Slooter
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: B C
authors.initials: BC
authors.lastname: Tanis
authors.forename: J M
authors.initials: JM
authors.lastname: Kemmeren
authors.forename: Y
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: A
authors.initials: A
authors.lastname: Algra
mesh_terms: D000328:Adult; D002545:Brain Ischemia; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000009:adverse effects*; D005165:Factor V; D005260:Female; D006579:Heterozygote; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D019851:Thrombophilia / Q000150:complications* / Q000453:epidemiology / Q000235:genetics
chemical_list: D003276:Contraceptives, Oral; C095381:factor V Leiden; D005165:Factor V; D042965:Methylenetetrahydrofolate Reductase (NADPH2)