Title
Reduced Response to Activated Protein C Is Associated with Increased Risk for Cerebrovascular Disease
Author
van der Bom, J.G.
Bots, M.L.
Haverkate, F.
Slagboom, P.E.
Meijer, P.
de Jong, P.T.V.M.
Hofman, A.
Grobbee, D.E.
Kluft, C.
Gaubius Instituut TNO
Publication year
1996
Abstract
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
Subject
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
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TNO identifier
233423
ISSN
0003-4819
Source
Annals of Internal Medicine, 125 (4), 265-269
Document type
article