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Previous Volume 332:912-917 April 6, 1995 Number 14 Next

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ABSTRACT

Background A specific point mutation in the gene coding for coagulation factor V is associated with resistance to degradation by activated protein C, a recently described abnormality of coagulation that may be associated with an increased risk of venous thrombosis. Whether this mutation also predisposes patients to arterial thrombosis is unknown, as is the value of screening for the mutation in order to define the risk of venous thrombosis among unselected healthy people.

Methods Among 14,916 apparently healthy men in the physicians' Health Study who provided base-line blood samples, 374 had myocardial infarctions, 209 had strokes, and 121 had deep venous thrombosis, pulmonary embolism, or both, during a mean follow-up of 8.6 years. We determined whether a mutation at nucleotide position 1691 of the factor V gene was present or absent in these 704 men and in an equal number of matched participants who remained free of vascular disease.

Results The prevalence of heterozygosity for the mutation among men who had myocardial infarctions (6.1 percent, P = 0.9) or strokes (4.3 percent, P = 0.4) was similar to that among men who remained free of vascular disease (6.0 percent). However, the prevalence of the mutation was significantly higher among men who had venous thrombosis, pulmonary embolism, or both (11.6 percent, P = 0.02). In adjusted analyses, the relative risk of venous thrombosis among men with the mutation was 2.7 (95 percent confidence interval, 1.3 to 5.6; P = 0.008). This increased risk was seen with primary venous thrombosis (relative risk, 3.5; 95 percent confidence interval, 1.5 to 8.4; P = 0.004) but not with secondary venous thrombosis (relative risk, 1.7; 95 percent confidence interval, 0.6 to 5.3; P = 0.3), and it was most apparent among older men. Specifically, the prevalence of the mutation among men over the age of 60 in whom primary venous thrombosis developed was 25.8 percent (relative risk, 7.0; 95 percent confidence interval, 2.6 to 19.1; P < 0.001).

Conclusions In a large cohort of apparently healthy men, the presence of a specific point mutation in the factor V gene was associated with an increased risk of venous thrombosis, particularly primary venous thrombosis. The presence of the mutation was not associated with an increased risk of myocardial infarction or stroke. This mutation appears to be the most common inherited factor thus far recognized that predisposes patients to venous thrombosis.

Source Information

From the Divisions of Preventive Medicine (P.M.R., C.H.H.) and Cardiovascular Disease (P.M.R., K.L.) and the Channing Laboratory (M.J.S.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; the Department of Cardiology, Children's Hospital (K.L.); the Department of Ambulatory Care and Prevention, Harvard Medical School (C.H.H.); the Departments of Nutrition (M.J.S.) and Epidemiology (M.J.S., C.H.H.), Harvard School of Public Health — all in Boston; and the Cardiovascular (P.R.E.) and Laboratory Medicine (J.P.M.) Divisions, Washington University School of Medicine, St. Louis.

Address reprint requests to Dr. Ridker at 900 Commonwealth Ave. E., Boston, MA 02215-1204.

Full Text of this Article

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Mutation in the Factor V Gene and the Risk of Myocardial Infarction
Emmerich J., Aiach M., Heinrich J., Budde T., Assmann G.
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N Engl J Med 1995; 333:880-881, Sep 28, 1995. Correspondence

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