Age-specific incidence rates of venous thromboembolism among heterozygous carriers of factor V Leiden mutation.
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.


METHODS
Prospective cohort study.


METHODS
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.


METHODS
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.
Ridker
P M
PM
Department of Medicine, Brigham and Womens' Hospital, Harvard Medical School, Boston, MA 02115, USA.
Glynn
R J
RJ
Miletich
J P
JP
Goldhaber
S Z
SZ
Stampfer
M J
MJ
Hennekens
C H
CH
D000328:Adult; D017677:Age Distribution; D000368:Aged; D005165:Factor V / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011486:Protein C / Q000378:metabolism; D013924:Thrombophlebitis / Q000453:epidemiology* / Q000235:genetics*; D014481:United States / Q000453:epidemiology
D011486:Protein C; D005165:Factor V