Effect of exogenous estrogen on atherothrombotic vascular disease risk related to the presence or absence of the factor V leiden mutation (resistance to activated protein C)
| Autor: | Trent Tracy, Robert N. Fontaine, James E. Lang, Ping Wang, Luann Sieve-Smith, Charles J. Glueck |
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| Rok vydání: | 1999 |
| Předmět: |
Risk
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Arteriosclerosis Hypercholesterolemia Polymerase Chain Reaction Thromboembolism hemic and lymphatic diseases Internal medicine medicine Factor V Leiden Humans Point Mutation Genetic Testing cardiovascular diseases Risk factor Activated Protein C Resistance Aged biology business.industry Contraindications Genetic Carrier Screening Point mutation Estrogen Replacement Therapy Factor V nutritional and metabolic diseases Odds ratio Middle Aged medicine.disease Lipids Cross-Sectional Studies Endocrinology Mutation (genetic algorithm) biology.protein Female Activated protein C resistance Cardiology and Cardiovascular Medicine business Protein C medicine.drug |
| Zdroj: | The American Journal of Cardiology. 84:549-554 |
| ISSN: | 0002-9149 |
| DOI: | 10.1016/s0002-9149(99)00375-6 |
| Popis: | Estrogen replacement therapy (ERT), which produces acquired resistance to activated protein C when superimposed on heritable resistance to activated protein C (the mutant Factor V Leiden trait), may promote venous and arterial thrombosis. In a cross-sectional study of 423 women referred for hyperlipidemic therapy (93 of whom [22%] were on ERT), our specific aim was to determine whether ERT and heterozygosity for the Factor V Leiden mutation and/or resistance to activated protein C interacted as risk factors for atherothrombosis. Of the 423 women, 168 (40%) had atherothrombosis, 19 (4%) were heterozygous for Factor V Leiden mutation or had resistance to activated protein C2 (Factor V Leiden mutation+), and 404 were wild-type normal for the Factor V gene and/or had resistance to activated protein Cor =2 (Factor V Leiden mutation-). By stepwise logistic regression, positive explanatory variables for atherothrombosis included hypertension (p = 0.002), age (p = 0.003), relatives with atherothrombosis (p = 0.002), anticardiolipin antibody immunoglobulin-M (p = 0.02), and a Factor V Leiden mutation*ERT interaction term where atherothrombosis events were more likely in 2 subgroups of women (ERT- and Factor V Leiden mutation-) or (ERT+ and Factor V Leiden mutation+) (p = 0.02). High-density lipoprotein cholesterol was inversely associated with atherothrombosis (p = 0.004). In a separate logistic regression model for the 213 women with a polymerase chain reaction measurement of the Factor V gene, ERT was protective (p = 0.008); the Factor V Leiden mutation was positively associated with atherothrombosis (p = 0.05). The atherothrombosis odds ratio risk for ERT (yes vs no) was 0.36 (95% confidence intervals [CI] 0.16 to 0.74, p = 0.007). The atherothrombosis risk odds ratio in women heterozygous for the Factor V Leiden mutation (vs normal) was 2.00 (95% CI 1.02 to 4.22, p = 0.05). ERT may be protective against atherothrombosis when the Factor V Leiden mutation is absent, whereas the Factor V Leiden mutation may increase risk for atherothrombosis, particularly in the presence of ERT. We suggest that the Factor V Leiden mutation be measured in all women on ERT or before beginning ERT to identify those heterozygous for the Factor V Leiden mutation (4%), in whom ERT is relatively or absolutely contraindicated because of increased risk for atherothrombosis and thromboembolism. A second, much larger group of women will also be identified without the factor V Leiden mutation (96%), in whom ERT may reduce the risk for atherothrombosis. |
| Databáze: | OpenAIRE |
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