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Circulation. 1998;98:2241-2247

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(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

Anna M. Thögersen, MD; Jan-Håkan Jansson, MD; Kurt Boman, MD; Torbjörn K. Nilsson, MD; Lars Weinehall, MD; Fritz Huhtasaari, MD; ; Göran Hallmans, MD

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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