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(Stroke. 1999;30:7-11.)
© 1999 American Heart Association, Inc.

Original Contributions

Elevated Tissue Plasminogen Activator Antigen and Stroke Risk

The Stroke Prevention in Young Women Study

Richard F. Macko, MD; Steven J. Kittner, MD, MPH; Anne Epstein, MS; D. Kim Cox, BS; Marcella A. Wozniak, MD, PhD; Robert J. Wityk, MD; Barney J. Stern, MD; Michael A. Sloan, MD; Roger Sherwin, PhD; Thomas R. Price, MD; Robert J. McCarter, PhD; Constance J. Johnson, MD; Christopher J. Earley, MD, PhD; David W. Buchholz, MD Paul D. Stolley, PhD

From the Departments of Neurology (R.F.M., S.J.K., A.E., D.K.C., M.A.W., M.A.S., T.R.P.) and Epidemiology and Preventative Medicine (S.J.K., M.A.S., R.S., T.R.P., R.J.M., P.D.S.), the University of Maryland at Baltimore; the Geriatrics Research, Education, and Clinical Center (R.F.M.), Baltimore Department of Veterans Affairs Medical Center, Baltimore, MD; the Department of Neurology (D.W.B., C.J.E., C.J.J., R.J.W.), Johns Hopkins University, Baltimore, MD; and the Department of Neurology (B.J.S.), Emory University School of Medicine, Atlanta, Ga.

Background and Purpose—Abnormalities in endogenous fibrinolysis are associated with an increased risk for stroke in men and older adults. We tested the hypothesis that elevated plasma tissue plasminogen activator (tPA) antigen, a marker for impaired endogenous fibrinolysis, is an independent risk factor for stroke in young women.

Methods—Subjects were 59 nondiabetic females ages 15 to 44 years with cerebral infarction from the Baltimore-Washington area and 97 control subjects frequency-matched for age who were recruited by random-digit dialing from the same geographic area. A history of cerebrovascular disease risk factors was obtained by face-to-face interview. Plasma tPA antigen was measured by enzyme-linked immunosorbent assay.

Results—Mean plasma tPA antigen levels were significantly higher in stroke patients than control subjects (4.80±4.18 versus 3.23±3.67 ng/mL; P=0.015). After adjustment for age, hypertension, cigarette smoking, body mass index, and ischemic heart disease, there was a dose-response association between tPA antigen and stroke with a 3.9-fold odds ratio of stroke (95% CI, 1.2 to 12.4; P=0.03) for the upper quartile (>4.9 ng/mL) of tPA antigen compared with the lowest quartile. The dose-response relationship between tPA antigen and stroke was equally present in white and nonwhite women, and further adjustment for total and HDL cholesterol levels only modestly attenuated this association.

Conclusions—This population-based case-control study shows that elevated plasma tPA antigen level is independently associated with an increased risk for ischemic stroke in nondiabetic females 15 to 44 years of age. These findings support the hypothesis that impaired endogenous fibrinolysis is an important risk factor for stroke in young women.

Key Words: cerebral infarction • fibrinolysis • risk factors • young adults • women

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