Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Kurt Huber, Siegmund Freud Private University, Vienna, Austria
- Second opponent: Associate Professor Christina Christersson, Uppsala University, Sweden
- Third member and chair of the evaluation committee: Professor Anne Cathrine Staff, University of Oslo
Chair of the Defence
Professor II Theis Tønnesen, University of Oslo
Principal Supervisor
MSc, PhD Vibeke Bratseth, Oslo University Hospital
Summary
Antiplatelet therapy has revolutionized the treatment of cardiovascular diseases (CVDs), however, despite the great advances; the risk of new thrombotic events remains high. There is a need for new biomarkers to identify patients at risk. In this thesis, the proteins von Willebrand factor (VWF) and its regulators ADAMTS13 and thrombospondin 1 (TSP1) were investigated. VWF is important for platelet activation and thrombus formation, while ADAMTS13 is an enzyme that inhibits VWF by cleaving it into smaller and less active fragments. TSP1 is believed to bind to VWF at the cleavage site, and thus compete with ADAMTS13, protecting VWF from degradation.
This thesis explored the VWF/ADAMTS13 axis in patients with high on-aspirin platelet reactivity, chronic coronary syndrome (CCS), and elderly with a recent myocardial infarction (MI). Patients were followed for 2 years for major adverse cardiovascular events (MACE). The hypotheses were that high VWF, low ADAMTS13 and high TSP1 levels were unbeneficial.
It has previously been published that the patients with high on-aspirin platelet reactivity had higher VWF levels. In this thesis, it was also shown that these patients had lower ADAMTS13 and higher VWF/ADAMTS13 ratio. In addition, higher VWF/ADAMTS13 ratio were associated with an increased risk of MACE in patients with CCS, while lower ADAMTS13 levels were associated with an increased risk of death in elderly patients with a recent MI. No associations between TSP1 and MACE were found.
Overall, the results indicate a role of VWF and ADAMTS13 in platelet reactivity in aspirin treated patients and of clinical outcome in patients with CVD. However, the associations with MACE were generally more modest than previously reported, and appear to be driven by death.
Additional information
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