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Reduced Response to Activated Protein C Is Associated with Increased Risk for Cerebrovascular Disease

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Author: Bom, J.G. van der · Bots, M.L. · Haverkate, F. · Slagboom, P.E. · Meijer, P. · Jong, P.T.V.M. de · Hofman, A. · Grobbee, D.E. · Kluft, C.
Institution: Gaubius Instituut TNO
Source:Annals of Internal Medicine, 4, 125, 265-269
Identifier: 233423
Keywords: Biology · anticoagulant agent · blood clotting factor 5 · protein C · aged · article · case control study · cerebrovascular disease · female · genetics · heart infarction · human · male · middle aged · mutation · pathophysiology · physiology · risk · Aged · Anticoagulants · Case-Control Studies · Cerebrovascular Disorders · Factor V · Female · Humans · Male · Middle Aged · Mutation · Myocardial Infarction · Odds Ratio · Protein C · Risk


Background: Resistance to activated protein C (APC), which results from various factors, including a mutation in the gene for coagulant factor V, has been associated with increased risk for venous thrombosis. However, its relation to arterial disease is still not well defined. Objective: To investigate the association of both response to APC and the factor V Leiden mutation with arterial disease. Design: Population-based case-control study. Setting: A district of Rotterdam, the Netherlands. Participants: 115 patients with a history of myocardial infarction; 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 genotyped for the Arg 506 to GIn mutation in the gene for coagulant factor V. Results: The prevalence of cerebrovascular disease increased gradually and corresponded to a decreasing response to APC (odds ratio per 1-unit decrease of response to APC, 1.43 [95% Cl, 1.12 to 1.81], adjusted for age and sex). Adjustment for the factor V mutation did not change the findings. We found no association between response to APC and myocardial infarction or between factor V mutation and cerebrovascular disease or myocardial infarction. Conclusions: Low response to APC is associated with an increased risk for cerebrovascular disease but not with an increased risk for myocardial infarction, independent of the factor V Leiden mutation. The association between the factor V Leiden mutation and cerebrovascular disease or myocardial infarction remains to be determined. Chemicals/CAS: Anticoagulants; Factor V, 9001-24-5; Protein C