Rheumatoid arthritis (RA) is a chronic inflammatory condition with poorly understood pathophysiology and increased cardiovascular risk. The mechanisms for increased cardiovascular risk are not fully known, however one novel mechanism explored in this thesis is autonomic nervous system (ANS) dysfunction. The thesis comprises of: a systematic literature review; two case-control studies (n=30 RA patients, n=34 controls; a longitudinal case-study (n=1 RA patient)); a cohort study (n=112 RA patients); and a randomised placebo controlled crossover study (n=10 healthy controls). The work presented in this thesis demonstrates that ANS dysfunction is prevalent in ~60 % of RA patients and characterised by heightened sympathetic outflow to the peripheral vasculature (determined by muscle sympathetic nerve activity using microneurography), depressed baroreflex control of heart rate (determined using the modified Oxford technique), depressed heart rate variability and heightened vascular responses to stressors (cold pressor test and mental stress). Inflammation was associated with ANS dysfunction, and may well contribute to the increased cardiovascular risk seen in RA. Further studies are required to: confirm these findings; determine whether therapeutic strategies to restore ANS function improve prognosis in RA; and further explore the precise mechanisms by which inflammatory cytokines may influence ANS function in health and disease.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:687483 |
| Date | January 2016 |
| Creators | Adlan, Ahmed |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/6705/ |
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