(Circulation. 1998;98:2241-2247.)
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports |
High Plasminogen Activator Inhibitor and Tissue Plasminogen Activator Levels in Plasma Precede a First Acute Myocardial Infarction in Both Men and Women
Evidence for the Fibrinolytic System as an Independent Primary Risk Factor
From the Department of Medicine (A.M.T.), Department of Clinical Chemistry (T.K.N.), and Departments of Nutritional Research and Pathology (G.H.), Umeå University Hospital; Department of Medicine-Geriatric, Skellefteå County Hospital (J.-H.J., K.B.) and Department of Epidemiology and Public Health (L.W.), University of Umeå; and Department of Medicine, Luleå Hospital (F.H.), Sweden.
Correspondence to Anna Margrethe Thögersen, Department of Medicine, Umeå University Hospital, Umeå, S-901 85 Sweden. E-mail anna.margrethe.thogersen{at}medicin.umu.se
Background—In patients with established ischemic heart disease, prospective cohort studies have indicated that plasminogen activator inhibitor (PAI-1), the inhibitor of the fibrinolytic system, may predict cardiovascular events. So far, there have been no primary prospective studies of PAI-1.
Methods and Results—The aim of the present study was to test whether plasma levels of PAI-1, tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), and thrombomodulin (TM) could predict the occurrence of a first acute myocardial infarction (AMI) in a population with high prevalence of coronary heart disease by use of a prospective nested case-control design. Mass concentrations of PAI-1 and tPA were significantly higher for the 78 subjects who developed a first AMI compared with the 156 references matched for age, sex, and sampling time; for tPA, this increase was independent of smoking habits, body mass index, hypertension, diabetes, cholesterol, and apolipoprotein A-I. The ratio of quartile 4 to 1 for tPA was 5.9 for a patient to develop a first AMI. The association between tPA and AMI was seen in both men and women. Increased levels of vWF were associated with AMI in a univariate analysis. High levels of TM were associated with AMI in women but not in men.
Conclusions—The plasma levels of PAI-1, tPA, and vWF are associated with subsequent development of a first AMI; for PAI-1 and tPA, this relation was found in both men and women. For tPA but not for PAI-1 and vWF, this association is independent of established risk factors.
Key Words: myocardial infarction • risk factors • plasminogen activators • von Willebrand factor
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