Cardiovascular Diseases Clinical Trial
To determine the effects of six genes on thrombotic risk factors known to be associated with the development of heart disease.
BACKGROUND:
Abnormalities in the plasminogen activator system have been implicated in the pathogenesis
of arterial and cerebral thrombosis. In particular, elevated plasma levels of plasminogen
activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (t-PA), and t-PA/PAI-1
complexes have been found to correlate with increased risk of myocardial infarction (MI)
and/or stroke. Vascular fibrinolytic balance is, to a large part, determined by the
competing effects of t-PA and PAI-1, and reflects a complex interplay between genetic and
environmental factors. The present collaboration focuses on the common hypothesis that the
association between activation of the renin-angiotensin-aldosterone system (RAAS) and
atherothrombotic events derives from an interaction between the RAAS and the fibrinolytic
system.
The study is part of an initiative "Thrombosis of the Arterial and Cerebral Vasculature: New
Molecular Genetic Concepts for Prevention and Treatment" which was released in April 1999.
The objective of the initiative is to establish collaborative teams of closely interacting
investigators with diverse, complementary areas of expertise to elucidate the molecular
genetic mechanisms of thrombosis in the arterial and cerebral vasculature.
DESIGN NARRATIVE:
The investigators will use two population-based samples of unrelated individuals to address
their aims: 1) study subjects in the PREVEND study in Groningen, The Netherlands in whom DNA
and plasma samples and clinical data have already been collected and 2) an estimated 2000
unrelated study subjects from Ghana, Africa in whom data need to be collected. The
collaborative study focuses on the common hypothesis that the association between activation
of the renin-angiotensin-aldosterone system (RAAS) and atherothrombotic events derives from
an interaction between the RAAS and the fibrinolytic system.
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