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Endothelial dysfunction in rheumatoid arthritis: the role of inflammation and classical cardiovascular disease risk factors on the microvasculature and the macrovasculature

Sandoo, Aamer (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of the joints with predominant symptoms of pain, swelling and stiffness. Patients with RA are at increased risk of cardiovascular disease (CVD). The exact mechanism for this is unknown, but RA disease-related inflammation has been postulated to affect the vasculature and contribute to endothelial dysfunction. The studies presented in this thesis examine vascular function in patients with RA and explore associations with disease-related inflammation as well as CVD risk factors. A cross-sectional study was carried out with 99 RA patients and 32 healthy control participants who underwent assessments of microvascular endothelial function, macrovascular endothelial function and arterial stiffness (AIx). Microvascular and macrovascular endothelial function were similar in RA patients and healthy control participants, but AIx was higher in the RA patients, as was global CVD risk. RA disease-related inflammation was not associated with microvascular or macrovascular endothelial-dependent function, however, global CVD risk inversely correlated with microvascular endothelial-dependent function and macrovascular endothelial-independent function. A longitudinal study was conducted in 23 RA patients starting on anti-tumor necrosis factor-α (anti-TNF-α) treatment and all the above-mentioned assessments were repeated after 2 and 12 weeks of treatment. Treatment, which was successful in reducing disease activity at 2 and 12 weeks, resulted in an improvement in microvascular endothelial-dependent function at 2 weeks, but not at 12 weeks. There was no change in macrovascular endothelial-dependent function or arterial stiffness at any time point, nor in global CVD risk. Finally, a systematic review of the literature pertaining to endothelial function in RA was performed. This revealed that, on the whole, the evidence supporting a relationship between endothelial function and disease-related inflammation was not strong. The findings of these studies suggest that classical CVD risk may be a better predictor of endothelial function in RA than disease-related inflammation.

Type of Work:Ph.D. thesis.
Supervisor(s):Veldhuijzen van Zanten, Jet and Carroll, Douglas and Kitas, George
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Sport and Exercise Science
Subjects:R Medicine (General)
QP Physiology
Institution:University of Birmingham
ID Code:1293
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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