Curriculum in cardiologyAssociation between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies
Section snippets
Literature search
Using a systematic search of MEDLINE electronic database between 1990 and 2002, we identified all studies correlating the factor V Leiden, prothrombin G20210A, or methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations with MI, ischemic stroke, or PVD. Terms used for the search were Medical Subject Heading (MeSH) terms and the text words “myocardial infarction,” “ischemic stroke,” or “peripheral vascular disease,” combined with “factor V,” “prothrombin,” “methylenetetrahydrofolate
Excluded studies
We excluded 1 study10 because it used a duplicate set of patients in separate studies.66 Four studies were excluded because we could not ascertain the absence of prior ischemic events in control subjects (inadequate control delineation).11, 12, 13, 14 Two studies were excluded because of an inadequate control population.15, 16 We eliminated 13 additional studies from consideration17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 because adequate definitions or diagnostic criteria for cited
Discussion
In our meta-analysis of >17,000 patients with coronary, cerebrovascular, or peripheral vascular events, several observations were made. First, the 3 common gene anomalies associated with venous thromboembolism (factor V Leiden mutation, prothrombin G20210A mutation, and MTHFR C677T mutation) increase the risk of arterial thrombotic events to comparatively modest degree. Second, the association is more robust in patients <55 years old and in women (for factor V Leiden and PT G20210A mutations).
Acknowledgements
We thank Dr Joseph Lau for his expert technical assistance with statistical analyses and data preparation; those who provided information about their past publications (Drs V. Arruda, A.J. Catto, V. de Stefano, J. Eikelboom, J. Genest, J. Holm, C. Irvine, R. Junker, W. Lalouschek, P.M. Manucci, G. Marchetti, M. Margaglione, A. Pezzini, W. Prohaska, W. Renner, P. Ridker, N. Samani, T. Tatlisumak, X.L. Wang, S. Whitehead, and D. Wilcken); and Robert Goldberg, PhD, and Frederick Spencer, MD, for
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