REDUCED RESPONSE TO ACTIVATED PROTEIN-C IS ASSOCIATED WITH INCREASED RISK FOR CEREBROVASCULAR-DISEASE

Background: Resistance to activated protein C (APC), which results fro m various factors, including a mutation in the gene for coagulant fact or V, has been associated with increased risk for venous thrombosis. H owever, its relation to arterial disease is sti II not well defined. O bjective: To investigate the association of both response to APC and t he factor V Leiden mutation with arterial disease. Design: Population- based case-control study. Setting: A district of Rotterdam, the Nether lands. Participants: 115 patients with a history of myocardial infarct ion; 112 patients with a history of stroke, transient ischemic attack, or both; and 222 age-matched controls without arterial disease chosen from among 7983 persons in the Rotterdam Study cohort. Patients using anticoagulant drugs were excluded. Measurements: Response to APC was determined in double-centrifuged platelet-poor plasma. Patients were g enotyped for the Arg 506 to Gln mutation in the gene for coagulant fac tor V. Results: The prevalence of cerebrovascular disease increased gr adually and corresponded to a decreasing response to APC (odds ratio p er 1-unit decrease of response to APC 1.43 [95% CI, 1.12 to 1.81], adj usted for age and sex). Adjustment for the factor V mutation did not c hange the findings. We found no association between response to APC an d myocardial infarction or between factor V mutation and cerebrovascul ar disease or myocardial infarction. Conclusions: Low response to APC is associated with an increased risk for cerebrovascular disease but n ot with an increased risk for myocardial infarction, independent of th e factor V Leiden mutation. The association between the factor V Leide n mutation and cerebrovascular disease or myocardial infarction remain s to be determined.