Author(s): Ridker PM, Glynn RJ, Miletich JP, Goldhaber SZ, Stampfer MJ
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.