Observations on autonomic and vascular function in patients with atrial fibrillation

Atrial fibrillation (AF) is related with significant morbidity and mortality. Adverse effects of AF are perceived to be due to haemodynamic changes leading to a prothrombotic state. Endothelial dysfunction, demonstrated by endothelial-dependent flow-mediated dilatation (FMD) is present in AF. Abnormalities of the autonomic nervous system are also involved in the pathogenesis of AF. Autonomic and vascular function in hypertensive patients with AF has yet to be described in detail. My thesis aims to provide an assessment into factors associated with adverse outcomes in AF by assessing plasma clot properties in AF and how it is affected by different anticoagulation strategies, renal impairment, endothelial function (using FMD); and autonomic function (using heart rate variability (HRV)). My work also explores the effect of a blood-pressure optimisation intervention on endothelial function. Finally, my work provides an assessment of autonomic and vascular function in patients with atrial high rate episodes (AHREs). I conclude that coagulation and fibrinolysis is affected by different anticoagulation agents and progressive renal impairment in AF. Presence of AF does not incrementally worsen endothelial dysfunction in hypertension patients (FMD 4.6%, 95% confidence interval (CI) [2.6 – 5.9%] (AF and hypertension group) vs FMD 2.6%, 95% CI [1.9 – 5.3%] (hypertension control group); p = 0.25), although the duration and frequency of AF (paroxysmal AF to permanent AF) does (FMD 3.1%, 95% CI [2.3 – 4.8%] (permanent AF group) vs FMD 5.9%, 95% CI [4.0 – 8.1%] (paroxysmal AF group); p = 0.02). There is potential for endothelial dysfunction to improve following optimisation of blood pressure (FMD 3.1%, 95% CI [2.3 – 4.8%] (baseline group) vs FMD 5.2%, 95% CI [3.9 – 6.5%] (follow up group); p = 0.09). AF, independent of hypertension, is characterised with marked HRV and is possibly related to vagal tone (rMSSD 106 ms, 95% CI [30 – 119] (AF and hypertension group) vs rMSSD 25 ms, 95% CI [20 – 32] (hypertension control group); p ≤ 0.01). HRV is higher in permanent AF compared to paroxysmal AF suggesting possible autonomic influence in its pathophysiology (rMSSD 115 ms, 95% CI [107 – 132] (permanent AF group) vs rMSSD 28 ms, 95% CI [21 – 41] (paroxysmal AF group); p ≤ 0.001). Endothelium-dependent FMD is impaired in patients with high AHRE burden (FMD 5.5% [95% CI: 3.4 – 7.6] (low AHRE burden group) vs 3.1 % [95% CI: 1.9 – 6.2] (high AHRE burden group); p = 0.04), while HRV derived indices of autonomic function were not affected by AHRE burden (rMSSD 40 ms, 95% CI [27 – 54] (low AHRE burden group) vs rMSSD 58 ms, 95% CI [39 – 77] (high AHRE burden group); p = 0.10)