FOR RELEASE: 4 p.m. ET, Thursday Jan. 7, 1999
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American Heart Association journal report: Elevated blood levels of inactive TPA linked to increased stroke risk in young women
DALLAS, Jan. 8 -- The amount of a clot-dissolver protein circulating in the blood may be a good predictor of an elevated stroke risk, according to a study in this month's Stroke: Journal of the American Heart Association.
The clot dissolver, tissue plasminogen activator (TPA), is used as a treatment to stop heart attacks. TPA, which is produced naturally in the blood, keeps the clotting mechanism from running amok and clogging blood vessels throughout the body. Blood levels of a protein known as the TPA antigen reflect both free active TPA and predominantly bound inactive TPA.
Previous studies have shown that blood levels of the TPA antigen are associated with stroke risk in older men, says the study's co-author, Richard F. Macko, M.D., assistant professor in neurology and gerontology at the University of Maryland School of Medicine and the Veteran's Administration Medical Center in Baltimore.
"Our study's findings support the hypothesis that an impaired blood clotting mechanism characterized by increases in the TPA antigen is an important predictor for increased risk of stroke for individuals in our study," he says.
The majority of TPA antigen exists as a complex with another protein, called plasminogen activator inhibitor, that inhibits its action. "Higher TPA antigen levels indicate higher levels of this inhibitor and lower levels of the active form of TPA," says Macko.
In the Stroke Prevention in Young Women Study, 59 women, age 16 to 44 years, who had a diagnosis of a first stroke, were matched with 97 women who had not had a stroke. The women were divided into four equal size groups depending on their blood level of TPA antigen. Those in the group with the highest blood levels of TPA antigen were nearly four times as likely to have suffered a stroke as women in the lowest-level group.
The study controlled for risk factors for stroke such as older age, high blood pressure, cigarette smoking, body mass index (an indication of girth), and coronary heart disease.
The association between TPA antigen and stroke was stronger than for high blood pressure or smoking, two major risk factors for stroke, the authors report. While the adjusted risk was 3.9 times higher for women with the highest blood levels of TPA antigen (compared with women with the lowest levels), it was 2.5 times higher for smokers (compared with nonsmokers) and 1.6 times higher for women with high blood pressure (compared with women without high blood pressure).
"The most important message from this study is that a disorder of blood clotting appear to be a strong and independent predictor for increased risk of stroke in young women," Macko says. "There aren't many known predictors of increased stroke risk in young people. Having reliable predictors of stroke risk can help researchers develop effective therapies to prevent stroke."
Some studies suggest that changing the clotting system -- which includes the TPA antigen -- through an exercise program, weight loss, or lowering blood cholesterol may reduce stroke risk, he says.
Macko cautions that prospective studies are needed to determine if a patient's TPA antigen blood level is a reliable predictor of stroke risk. Further studies also are needed to differentiate genetic from environmental factors that raise TPA antigen blood levels and to investigate the potential health benefits of therapies aimed at lowering those levels.
Co-authors of this study include Steven J. Kittner, M.D., M.P.H.; Anne Epstein, M.S.; D. Kim Cox, B.S.; Marcella A. Wozniak, M.D, Ph.D.; Robert J. Wityk, M.D.; Barney J. Stern, M.D.; Michael A. Sloan, M.D.; Roger Sherwin, Ph.D.; Thomas R. Price, M.D.; Robert J. McCarter, Ph.D.; Constance J. Johnson, M.D.; Christopher J. Earley, M.D.; David W. Buchholz, M.D.; and Paul D. Stolley, Ph.D.
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NR 98-4602 (Stroke/Macko) Media advisory: Dr. Macko can be reached by phone at (410) 605-7060; or by fax at (410) 605 7937. (Please do not publish telephone number.)
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