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Age-Specific Incidence Rates of Venous Thromboembolism among Heterozygous Carriers of Factor V Leiden Mutation

Paul M. Ridker, MD; Robert J. Glynn, PhD; Joseph P. Miletich, MD; Samuel Z. Goldhaber, MD; Meir J. Stampfer, MD; and Charles H. Hennekens, MD
[+] Article, Author, and Disclosure Information

For author affiliations and current author addresses, see end of text. Grant Support: In part by a Clinician Scientist Award from the American Heart Association (Dr. Ridker) and by grants HL-26490, HL-34595, CA-42182, and CA-40361 from the National Institutes of Health, Bethesda, Maryland. Requests for Reprints: Paul M. Ridker, MD, Department of Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02115. Current Author Addresses: Drs. Ridker and Goldhaber: Division of Cardiovascular Disease, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02215.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;126(7):528-531. doi:10.7326/0003-4819-126-7-199704010-00005
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Background: Previous reports suggest that younger carriers of the factor V Leiden mutation are at greater risk for venous thromboembolism than are older carriers. However, available data on thromboembolic risk are limited.

Objective: To determine age-specific incidence rates of venous thromboembolism associated with the factor V Leiden mutation.

Design: Prospective cohort study.

Patients: 14 916 initially healthy men participating in the Physicians' Health Study who were followed from 1982 to August 1994 for the occurrence of deep venous thrombosis or pulmonary embolism.

Measurements: Polymerase chain reaction was used to determine factor V Leiden mutation status in 156 study participants who developed venous thromboembolism during follow-up and in 2406 study participants who remained free of vascular disease.

Results: Risks for venous thromboembolism in heterozygous carriers of factor V Leiden mutation increased with age at a rate significantly greater than that in noncarriers. Whereas incidence rates of venous thromboembolism were similar in men with and men without the factor V Leiden mutation who were younger than 50 years of age, incidence rate differences (per 1000 person-years of observation) between affected and unaffected men increased significantly from 1.23 (95% CI, −0.4 to 2.9) for those aged 50 to 59 years to 1.61 (CI, −0.5 to 3.7) for those aged 60 to 69 years of age to 5.97 (CI, 0.6 to 11.3) for those aged 70 years or older (P for trend = 0.008). For idiopathic venous thromboembolism, age-specific incidence rate differences between men with and without the factor V Leiden mutation increased significantly with age (P = 0.017). However, no significant relation was found for secondary events (P > 0.2).

Conclusions: The findings support the hypothesis that the pathogenesis of venous thromboembolism involves acquired as well as genetic risk factors and indicate that determination of factor V Leiden mutation status should not be limited to young patients.


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Figure 1.
Estimated age-specific incidence rates for venous thromboembolism among men with (dashed lines) and men without (solid lines) factor V Leiden mutation.Left.Middle.Right.

Any venous thromboembolism. Idiopathic venous thromboembolism. Venous thromboembolism associated with cancer or surgery.

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