Trial lecture title: Major determinants of thromboembolic risk in RA: relevance for targeted therapies.
Th ordinary opponents are:
- First opponent: Lotta Ljung, University Hospital of Umeå, Sweden
- Second opponent: Zoltán Szekanecz, Professor of Medicine, Head of Rheumatology Department at University of Debrecen Medical and Health Sciences Center, Hungary
- Leader of the committee: Professor Cecilie Johannessen Landmark, OsloMet, Norway
The leader of the public defence is Associate Professor Jonas Debesay, OsloMet.
The main supervisor is Ivana Hollan, MD, PhD, Lillehammer Hospital for Rheumatic Diseases
The co-supervisors are:
- Stefan Agewall, Oslo University Hospital and University of Oslo
- Torstein Lyberg, Oslo University Hospital
- Milada Cvancarova Småstuen, OsloMet
Thesis abstract
In order to improve treatment of atherosclerosis and its accelerated form in inflammatory arthritis (IA), as well as of IA themselves, it is essential to improve insights into pathophysiology of these conditions, and to find optimal biomarkers for monitoring IA activity and cardiovascular (CV) risk.
Therefore, we focused on three parameters suspected to be involved in pathophysiology of CV disease (CVD) and/or inflammation: endothelial function (EF), pentraxin 3 (PTX3) and selenium levels.
Impaired EF, one of the first steps of atherosclerosis, is a valuable biomarker of CV risk. PTX3, an important molecule of the innate immune system, has been proposed to be a useful biomarker of both inflammation and CV risk due to its production in the inflamed tissue and fast response.
Selenium deficit appears to enhance CVD risk and inflammation.
A prospective longitudinal observational study
We examined patients from PSARA, a prospective longitudinal observational study comprising 140 patients with rheumatoid arthritis, psoriasis arthritis or ankylosing spondylitis starting with methotrexate and/or anti-TNF therapy due to active disease.
We assessed the patients at baseline and after six weeks and six months of treatment. In IA patients with endothelial dysfunction, EF rapidly improved with antirheumatic treatment, independent of change in inflammatory status. Hence, besides the anti-inflammatory effects, also other modes of actions of disease modifying antirheumatic drugs may contribute to their atheroprotective effects.
The IA patients had increased PTX3 levels that, in contrast to other inflammatory factors, did not change with treatment. Hence, the high PTX3 levels in IA might reflect an ongoing immune process not modifiable by the given antirheumatic treatment.
Selenium levels (72µg/L) were within reference range but below the limit of 80-85 µg/L that is considered optimal for CVD protection. Thus, further research is necessary to clarify if selenium insufficiency contributes to increased CV risk in IA, or if the previously observed link between selenium levels and CV risk is caused by underlying inflammation.
Intriguingly, selenium levels increased with treatment, potentially due to inhibition of selenium consuming proinflammatory processes.
Taken together, our results can contribute to better insights into the pathogenesis in IA and the associated accelerated CVD, and in pharmacological actions of two of the most common antirheumatic regimens, and consequently facilitate development of better management strategies for these conditions.
