Factor V Leiden and the Risk for Venous Thromboembolism in the Adult Danish Population

  1. Klaus Juul, MD;
  2. Anne Tybjærg-Hansen, MD, DMSc;
  3. Peter Schnohr, MD; and
  4. Børge G. Nordestgaard, MD, DMSc
  1. From Herlev University Hospital, Herlev, Denmark; Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, and The Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen, Denmark.

    Abstract

    Background: Odds ratios for venous thromboembolism (deep venous thrombosis and pulmonary embolism) derived from case–control studies range from 3 to 16 for heterozygotes compared with noncarriers and up to 79 for homozygotes compared with noncarriers.

    Objective: To estimate risks for venous thromboembolism in the adult Danish population according to factor V Leiden genotype.

    Design: Cohort study with 23 years of follow-up.

    Setting: Adult Danish population.

    Participants: 9253 randomly selected individuals.

    Measurements: Hospitalization and death from venous thromboembolism, factor V Leiden genotype, and additional thromboembolic risk factors.

    Results: Adjusted hazard ratios in heterozygotes and homozygotes compared with noncarriers were 2.7 (95% CI, 1.8 to 3.8) and 18 (CI, 4.1 to 41) for venous thromboembolism overall, 2.4 (CI, 1.3 to 3.8) and 22 (CI, 0 to 60) for deep venous thrombosis, and 3.0 (CI, 1.7 to 4.9) and 11 (CI, 0 to 33) for pulmonary embolism. The lowest absolute 10-year risks for venous thromboembolism in factor V Leiden heterozygotes and homozygotes—0.7% (CI, 0.5% to 1.0%) and 3% (CI, 1% to 8%)—were found in nonsmokers younger than 40 years of age with a body mass index below 25 kg/m2; the corresponding highest risks—10% (CI, 7% to 14%) and 51% (CI, 13% to 100%)—were found in smokers older than 60 years of age with a body mass index above 30 kg/m2.

    Conclusions: Hazard ratios for venous thromboembolism in factor V Leiden heterozygotes and homozygotes compared with noncarriers in the adult Danish population were approximately 3 and 18, respectively. The simultaneous presence of smoking, obesity, and old age resulted in absolute 10-year thromboembolic risks of 10% in heterozygotes and 51% in homozygotes.

    Article and Author Information

    • Acknowledgments: The authors thank Hanne Damm for technical assistance and the participants of the Copenhagen City Heart Study for their willingness to participate.

    • Grant Support: By grants from the Danish Heart Foundation, the Danish Medical Research Council, Chief Physician Johan Boserup and Lise Boserup's Fund, Lykfeldt's Fund, Dagmar Marshall's Fund, Wedelborg's Fund, Lily Benthine Lund's Fund, the Beckett Fund, and P. Carl Petersen's Fund.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Børge G. Nordestgaard, MD, DMSc, Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; e-mail, brno{at}herlevhosp.kbhamt.dk.

    • Current Author Addresses: Drs. Juul and Nordestgaard: Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.

    • Dr. Tybjærg-Hansen: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 3, DK-2100 Copenhagen, Denmark.

    • Dr. Schnohr: The Copenhagen City Heart Study, Bispebjerg University Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark.

    • Author Contributions: Conception and design: K. Juul, A. Tybjærg-Hansen, P. Schnohr, B.G. Nordestgaard.

    • Analysis and interpretation of the data: K. Juul, A. Tybjærg-Hansen, B.G. Nordestgaard.

    • Drafting of the article: K. Juul.

    • Critical revision of the article for important intellectual content: K. Juul, A. Tybjærg-Hansen, B.G. Nordestgaard.

    • Final approval of the article: K. Juul, A. Tybjærg-Hansen, B.G. Nordestgaard.

    • Statistical expertise: K. Juul, A. Tybjærg-Hansen, B.G. Nordestgaard.

    • Obtaining of funding: K. Juul, A. Tybjærg-Hansen, B.G. Nordestgaard.

    • Collection and assembly of data: K. Juul, A. Tybjærg-Hansen, P. Schnohr, B.G. Nordestgaard.

    Responses to this article

    • Factor V Leiden: a difference in cohort and case-control studies?
      • Jan P Vandenbroucke and
      • Frits R. Rosendaal
      Ann Intern Med published online October 26, 2009

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    1. Ann Intern Med March 2, 2004 vol. 140 no. 5 330-337
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