An impaired fibrinolytic function due to elevated plasma levels of
plasminogen activator inhibitor (PAI)-1 activity or
tissue plasminogen activator (
tPA) antigen is correlated with the development of
myocardial infarction (MI) in patients with manifest
coronary heart disease. Recently, methods for determining the specific tPA/inhibitor complexes constituting
tPA antigen in plasma have become available. In the Stockholm Heart Epidemiology Program (SHEEP) study, 86 of 1212 MI patients, subjected to blood sampling in a metabolically stable period, suffered reinfarction before the end of 1996. These individuals have been compared with an approximately equal number of matched MI patients without recurrence and a group of matched healthy control subjects regarding the plasma concentrations of some
hemostatic factors. The
hemostatic compounds studied (
fibrinogen,
von Willebrand factor,
tPA antigen, PAI-1, and the tPA/PAI-1 complex) were typically higher in the groups (men and women) with recurrence of MI compared with those without. The plasma concentrations were also typically higher in the pooled groups of patients compared with the groups of healthy control subjects. The largest between-group differences were found for the plasma tPA/PAI-1 complex. The crude odds ratio for reinfarction associated with higher concentration (>/=75th percentile among the control subjects) of tPA/PAI-1 was 1.8 (95% CI 1.1 to 3.1); the corresponding crude odds ratio for
von Willebrand factor was 2.3 (1. 3 to 4.0). The tPA/PAI-1 complex correlated strongly with
PAI-1 and
tPA antigen in all groups and with serum
triglycerides and body mass index in all groups except for women with reinfarction. An increased plasma level of tPA/PAI-1 complex is a novel risk marker for recurrent MI in men and women. Most likely, increased plasma levels of tPA/PAI-1 complex reflect impaired fibrinolysis, because the correlation with
PAI-1 is strong. Further support is obtained indicating that the plasma concentration of
von Willebrand factor is also an important risk marker for recurrent MI.