Thursday, September 02, 1999

Study links gene with blood clots


Estrogen raises risk for some

BY TIM BONFIELD
The Cincinnati Enquirer

        A Cincinnati researcher says women should get a blood test before they take birth control pills or hormone replacement therapy. The reason: to check for a genetic disorder that makes about 5 percent of women as much as 100 times more likely to develop blood clots that can lead to stroke, heart disease or heart attacks.

        The recommendation comes from a study by the Jewish Hospital Cholesterol Center, led by Dr. Charles Glueck, published in Wednesday's edition of the American Journal of Cardiology.

        Dr. Glueck's recommendation has potentially far-reaching implications because tens of millions of women take birth control pills or hormone replacement therapy.

        The study found women who have a mutated version of a common gene known as Factor V are more likely to have rough surfaces inside their artery walls, which makes them much more likely to build up artery-clogging plaque.

        The estrogen in birth control pills and hormone replacement therapy aggravates the condition.

        In women with the mutated gene, estrogen can increase the risk of a blood clot 100-fold, Dr. Glueck said. But for women with the normal Factor V gene, estrogen has the opposite effect: It lowers the risk of blood clots.

        “Most women who have the mutant gene have no idea they have it,” Dr. Glueck said. “Therefore, our findings suggest that all women who are being prescribed birth control pills or hormone replacement therapy receive a test called a Factor V genetic test.”

        Medical researchers have been debating the pros and cons of estrogen therapy for several years. For most women, it is thought to reduce the risk of osteoporosis and heart disease. But there have been concerns about estrogen increasing the risks of breast cancer and blood clots, and how much it protects against heart disease.

        Some doctors, who say the benefits of hormone replacement therapy far outweigh the risks of blood clotting, disagree with Dr. Glueck's calls for wide-scale genetic screening.

        “There is a group of women who should be screened, but to uniformly recommend that every woman consider having a genetic test, we're not ready for that,” said Dr. Molly Katz, a Cincinnati gynecologist and past president of the Academy of Medicine of Cincinnati.

        Officials with the American Heart Association, contacted Wednesday, had no comment about the study because they had not seen it.

        Dr. Glueck said the Factor V mutation goes a long way toward explaining why hormone replacement therapy causes blood clots.

        The blood test means women can be more certain whether they will benefit or suffer from estrogen in birth control pills and hormone replacement therapy, Dr. Glueck said.

        It could cost $25-$30 for a blood clotting test called “resistance to activated protein C,” or about $75 for a more accurate DNA test for the Factor V mutation.

        Dr. Katz said it would be unlikely that insurance companies would pay for such tests. And if doctors refused to prescribe birth control pills or hormone replacement therapy without the tests, the consequences for some women would be even worse than the threat of blood clotting.

        “There's no question that this recommendation is expensive. But it could reduce a lot of disease, death and suffering,” Dr. Glueck said.

        Researchers have known about the Factor V mutation and its link to blood clots in the veins for about five years. The link between the mutation, estrogen and the arteries, which carry oxygen-rich blood from the heart and lungs, is new.

        The artery connection is important because blood clots in arteries are more likely to kill than blood clots in veins, Dr. Glueck said.

        The mutation, discovered by European researchers and named after the city of Leiden, is most common among Caucasian women. About 6 percent of all Caucasian women have the mutation, compared with about 3 percent of African-American and Hispanic women. The mutation is even less common among Asian women.

        The genetic link to estrogen and blood clotting adds a new wrinkle to the growing public understanding of the differences in heart disease risk between women and men.

        Other recent studies have found that the signs of heart attack often are more subtle for women than men, and that doctors often treat women less aggressively when they show signs of heart disease.

        “When women hit menopause, many have assumed that (estrogen therapy) would protect them. That's still true for the vast majority of women, but for others it can be a serious risk,” Dr. Glueck said.

       



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