Hereditary deficiency of protein C or protein S confers increased risk of arterial thromboembolic events at a young age: results from a large family cohort study.
Fulltext:
70054.pdf
Embargo:
until further notice
Size:
187.4Kb
Format:
PDF
Description:
Publisher’s version
Publication year
2008Source
Circulation, 118, 16, (2008), pp. 1659-67ISSN
Publication type
Article / Letter to editor
Display more detailsDisplay less details
Organization
Cardiology
Internal Medicine
Journal title
Circulation
Volume
vol. 118
Issue
iss. 16
Page start
p. 1659
Page end
p. 67
Subject
UMCN 2.1: Heart, lung and circulationAbstract
BACKGROUND: Whether hereditary protein S, protein C, or antithrombin deficiency is associated with arterial thromboembolism (ATE) and whether history of venous thromboembolism in these subjects predisposes them to subsequent ATE have yet to be determined. METHODS AND RESULTS: On the basis of pedigree analysis, we enrolled a total of 552 subjects (52% women; mean age, 46+/-17 years), belonging to 84 different kindreds, in this retrospective family cohort study. Detailed information on previous episodes of venous thromboembolism, ATE, anticoagulant use, and atherosclerosis risk factors was collected. Primary study outcome was objectively verified symptomatic ATE. Of 552 subjects, 308 had protein S (35%), protein C (39%), or antithrombin (26%) deficiency. Overall, annual incidences of ATE were 0.34% (95% confidence interval [CI], 0.23 to 0.49) in deficient versus 0.17% (95% CI, 0.09 to 0.28) in nondeficient subjects; the hazard ratio was 2.3 (95% CI, 1.2 to 4.5). Because the risk hazards varied over lifetime, we performed a time-dependent analysis. After adjusting for atherosclerosis risk factors and clustering within families, we found that deficient subjects had a 4.7-fold (95% CI, 1.5 to 14.2; P=0.007) higher risk for ATE before 55 years of age versus 1.1 (95% CI, 0.5 to 2.6) thereafter compared with nondeficient family members. For separate deficiencies, the risks were 4.6- (95% CI, 1.1 to 18.3), 6.9- (95% CI, 2.1 to 22.2), and 1.1- (95% CI, 0.1 to 10.9) fold higher in protein S-, protein C-, and antithrombin-deficient subjects, respectively, before 55 years of age. History of venous thromboembolism was not related to subsequent ATE (hazard ratio, 1.1; 95% CI, 0.5 to 2.2). CONCLUSIONS: Compared with nondeficient family members, subjects with protein S or protein C deficiency but not antithrombin deficiency have a higher risk for ATE before 55 years of age that is independent of prior venous thromboembolism.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122509]
- Faculty of Medical Sciences [90373]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.