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

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.