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J Am Coll Cardiol, 2001; 37:215-218 © 2001 by the American College of Cardiology Foundation |
* Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Division of Cardiovascular Disease, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
|| Division of Laboratory Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
¶ University of Miami School of Medicine, Miami, Florida, USA
Manuscript received May 1, 2000; revised manuscript received August 9, 2000, accepted September 29, 2000.
Reprint requests and correspondence: Dr. Paul Ridker, Brigham and Women’s Hospital, 900 Commonwealth Ave. East, Boston, Massachusetts 02115
pridker{at}partners.org
OBJECTIVES
The study was done to determine whether the G20210A mutation in the prothrombin gene increases the risk of recurrent venous thromboembolism (VTE), both alone and in combination with factor V Leiden.
BACKGROUND
Several inherited defects of coagulation are associated with increased risk of first VTE, including a recently identified G20210A mutation in the prothrombin gene. However, whether the presence of this mutation confers an increased risk of recurrent venous thromboembolism is controversial.
METHODS
A total of 218 men with incident venous thromboembolism were genotyped for the prothrombin mutation and for factor V Leiden and were followed prospectively for recurrent VTE over a follow-up period of 7.3 years.
RESULTS
A total of 29 men (13.3%) suffered recurrent VTE. Five of the 14 carriers of the prothrombin mutation developed recurrent VTE (35.7%; incidence rate = 8.70 per 100 person-years), while 24 of 204 individuals who did not carry the prothrombin mutation developed recurrent VTE (11.8%; incidence rate = 1.76 per 100 person-years). Thus, presence of the G20210A mutation was associated with an approximate fivefold increased risk for recurrent VTE (crude relative risk [RR] 4.93; 95% confidence interval [CI] 1.9–12.9; p = 0.001; age-, smoking-, and body mass index-adjusted RR 5.28; 95% CI 2.0–14.0; p = 0.001). In these data, recurrence rates were similar among those with an isolated mutation in the prothrombin gene (18.2%) as compared to those with an isolated factor V Leiden mutation (19.2%). However, all three study participants who carried both mutations (100%) suffered a recurrent event during follow-up.
CONCLUSIONS
In a prospective evaluation of 218 men, the presence of prothrombin mutation was associated with a significantly increased risk of recurrent VTE, particularly among those who co-inherited factor V Leiden.
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