Watson, Timothy J. (2011)
M.D. thesis, University of Birmingham.
Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice with rapidly rising prevalence and incidence predominantly due to advancing age in Western populations. Of particular concern however is the strong relationship between AF and stroke. This relates to a number of factors, but there is an emerging body of evidence to suggest that AF confers a hypercoagulable state. Disruption of endothelial homeostasis (damage vs. repair) is thought to be central to this process. The endothelium appears to be damaged both by AF and various other vascular diseases (e.g. hypertension) that frequently co-exist with the arrhythmia, with similar disruption to endothelial repair (normally effected by endothelial progenitor cells). Endothelial damage seems to be an essential prerequisite to thrombogenesis in AF. Significantly, the endothelium also links a number of processes including inflammation, growth factors, the renin-angiotensin-aldosterone system among others, which may directly or indirectly lead to activation of the coagulation cascade. This thesis investigates the relationship between the temporal pattern of AF (paroxysmal, persistent, permanent) and established markers of endothelial dysfunction (vonWillebrand factor, vWf; soluble E-selectin, sEsel), angiogenesis (vascular Endothelial Growth Factor, VEGF), apoptosis (soluble Fas/Fas ligand, sFas/sFasL) and inflammation (C-reactive protein, CRP; Interleukin-6, IL-6) in AF with particular reference to circulating progenitor cells (CPCs) as a novel marker of endothelial health/angiogenesis. Additionally the impact of restoration of sinus rhythm using electrical cardioversion on these indices and the relevance of the AF arrhythmia burden in influencing these markers is investigated. In conclusion, the endothelium seems to be a central link through which all three components of Virchow’s triad interact in AF. This thesis finds a possible link for CPCs to interact with various other reported aberrancies of the hypercoagulable state in this process. Also reported is a modest alteration in CPC counts following restoration of sinus rhythm, however, only limited numbers of patients were assessed and this requires examination with a more in depth study. Finally, the thesis has also examined the role of paroxysmal AF in influencing surrogate markers of the hypercoagulable state, but failed to find any significant differences on the basis of the arrhythmia burden. These findings must however been considered in light of numerous study limitations, the most notable of which is limited statistical power.
|Type of Work:||M.D. thesis.|
|Supervisor(s):||Lip, Gregory Y. H.|
|School/Faculty:||Colleges (2008 onwards) > College of Medical & Dental Sciences|
|Department:||School of Clinical and Experimental Medicine, Centre for Cardiovascular Sciences|
|Keywords:||atrial fibrillation; endothelial progenitor cells; angiogenesis; growth factors; apoptosis; inflammation; stroke|
|Subjects:||RC Internal medicine|
|Institution:||University of Birmingham|
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