They found that women using OCs who were heterozygous for factor V Leiden (OR, 11.2; 95% CI, 4.2 29.0) and methyl tetrahydrofolate reductase or MTHFR 677TT mutation (OR, 5.4; 95% CI, 2.4 12.0) were at increased risk of IS. There may have been some synergism between OCs and these mutations, because the increased risk was not evident in nonusers with these mutations.225 In addition, this study also showed an association with a genetic variation of fac- In the assessment of acquired antiphospholipid antibodies, the presence of 2 glycoprotein-1 antibodies was associated with 2.3-fold increased odds of stroke (95% CI, 1.4 3.7), but there was no association with anticardiolipin or antiprothrombin antibodies. The prevalence of lupus anti- coagulant was 17% in women with IS, and the OR was very The OR increased to 201 (95% CI, 22.1 1828.0) in women who were also using OCs, although this was based on a very small number of outcomes. This is another example of the amplification of IS risk in a condition that is already associated with arterial thromboembolism and VTE.227 The RATIO investigators also assessed the association between OC use and endothelial dysfunction. They reported that an increase in von Willebrand factor levels and low ADAMTS13 levels were associated with increased odds of IS and MI in young women in the RATIO cohort, with a further Table 8. 