Bruce M. Psaty, M.D., Ph.D.Institution: University of Washington
Drug-gene interaction associated with heart attacks in hypertensive women on hormone replacement
A study by researchers at the University of Washington shows a possible link between the presence of a genetic variant associated with blood clotting and the risk of non-fatal heart attacks in hypertensive women who take hormone replacement therapy (HRT). The study was led by Bruce M. Psaty, M.D., Ph.D., a professor of medicine, epidemiology and health services and co-director of the UW's Cardiovascular Health Research Unit.
The team studied the prothrombin gene. Prothrombin is a protein essential for the clotting of blood. The prothrombin gene variant occurs in 2 percent to 4 percent of the population and increases the risk of blood clots in the legs.
In women with hypertension, the effects of HRT on heart attack risk depended on the prothrombin gene. Among women who did not have the genetic variant, HRT users had a slightly lower risk of heart attack than women who did not use HRT. Among women with the prothrombin gene variant, however, HRT users had an eight-fold higher risk of a heart attack than women who did not use HRT.
Although the number of women with the prothrombin variant was small, the heart attack risk associated with HRT use differed markedly between those with and without the prothrombin variant. The interaction persisted when the investigators adjusted for many known risk factors for heart attack, and it was specific to the prothrombin variant.
The researchers looked for the prothrombin-HRT interaction in women without hypertension, but did not find evidence of it. If the study's findings are confirmed or extended in future studies, physicians may use the results of one or more genetic tests to better predict the major health risks and benefits of hormone replacement therapy for individual postmenopausal women.
"To recommend genetic screening, we would need to know that the health benefits exceed the risks, " Psaty said. "Now that we have the sequence of the human genome in hand, the task of assessing its clinical usefulness is just beginning."
This work was funded by grants from the National Heart, Lung, and Blood Institute and a National Center American Heart Association Patient Care and Outcomes Research Award.