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.
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.


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.
Thögersen
A M
AM
Department of Medicine, Clinical Chemistry, and Nutritional Research and Pathology. Umeå University Hospital, University of Umeå, Sweden. anna.margrethe.thogersen@medicin.umu.se
Jansson
J H
JH
Boman
K
K
Nilsson
T K
TK
Weinehall
L
L
Huhtasaari
F
F
Hallmans
G
G
D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology; D015849:Plasminogen Inactivators / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D013548:Sweden; D010959:Tissue Plasminogen Activator / Q000097:blood*
D015415:Biomarkers; D015849:Plasminogen Inactivators; D019314:Dehydroepiandrosterone Sulfate; D010959:Tissue Plasminogen Activator