167. Reduced response to activated protein C is associated with risk of stroke and transient ischaemic attack

Objective: To investigate the association of activated protein C (APC) response and of the factor V Leiden mutation with myocardial infarction, stroke and transient ischémie attack. Design: Population-based case control study. Setting: A district of Rotterdam, the Netherlands. Participants: From the Rotterdam Study cohort that consists of 7983 men and women aged 55 years and over, we selected 115 subjects with a history of myocardial infarction, 112 with a history of stroke and/or transient ischaemic attack and 222 age matched control subjects without arterial disease. Subjects using anticoagulant drugs were not selected. Measurements: APC response was determined in double centrifuged platelet poor plasma. All subjects were genotyped for presence of the G1691A mutation in the factor V gene. Results are adjusted for age and gender. Results: The risk of cerebrovascular disease gradually increased with decreasing APC response. An APC response lower than 3.5 was associated with an increased risk of cerebrovascular disease compared to an APC response above 5 (odds ratio 2.4 (95% CI 1.1, 5.2)). Additional adjustment for the factor V mutation did not change the findings. APC response was not associated with myocardial infarction. The risks of cerebrovascular disease and myocardial infarction were not increased in subjects with the factor V mutation. Conclusion: A decrease in APC response is associated with an increased risk of cerebrovascular disease, but not of myocardial infarction. The risk was independent of the factor V Gl 691A mutation. The factor V mutation is not associated with cerebrovascular disease or with myocardial infarction.