© 2000 American Heart Association, Inc.
Thrombosis |
Plasma Levels of Tissue Plasminogen Activator/Plasminogen Activator Inhibitor-1 Complex and von Willebrand Factor Are Significant Risk Markers for Recurrent Myocardial Infarction in the Stockholm Heart Epidemiology Program (SHEEP) Study
From the Department of Clinical Chemistry (B.W.) and the Division of Cardiovascular Medicine (U.d.F.), Karolinska Hospital; the Department of Epidemiology (T.A., C.R., A.A.) and Cardivascular Epidemiology (U.d.F.), Institute of Environmental Medicine; and the Division of Social Medicine (J.H.), Department of Public Health Sciences, Karolinska Institute, Stockholm, Sweden.
Correspondence to Prof Björn Wiman, Department of Clinical Chemistry, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail bjorn.wiman{at}lab.ks.se
Abstract—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.
Key Words: fibrinolysis • hemostasis • myocardial infarction • risk markers
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