Elevated tissue plasminogen activator antigen and stroke risk - The strokeprevention in young women study

Background and Purpose-Abnormalities in endogenous fibrinolysis are associa ted with an increased risk for stroke in men and older adults. We tested th e hypothesis that elevated plasma tissue plasminogen activator (tPA) antige n, a marker for impaired endogenous fibrinolysis, is an independent risk fa ctor for stroke in young women. Methods-Subjects were 59 nondiabetic females ages 15 to 44 years with cereb ral infarction from the Baltimore-Washington area and 97 control subjects f requency-matched for age who were recruited by random-digit dialing from th e same geographic area. A history of cerebrovascular disease risk factors w as obtained by face-to-face interview. Plasma tPA antigen was measured by e nzyme-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 associati on 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 anti gen compared with the lowest quartile. The dose-response relationship betwe en tPA antigen and stroke was equally present in white and nonwhite women, and further adjustment for total and HDL cholesterol levels only modestly a ttenuated this association. Conclusions-This population-based case-control study shows that elevated pl asma tPA antigen level is independently associated with an increased risk f or ischemic stroke in nondiabetic females 15 to 44 years of age. These find ings support the hypothesis that impaired endogenous fibrinolysis is an imp ortant risk factor for stroke in young women.