Improved Characterisation of Hypertension in Atrial Fibrillation: Role of Central Blood Pressure and Aortic Stiffness Assessment

Abstract

Atrial Fibrillation (AF) is the most common sustained arrhythmia; however its underlying mechanism is yet to be fully characterised. Emerging data have elucidated the strong correlation of the arrhythmia with uncontrolled cardiovascular (CV) risk factors. Amongst these, hypertension is the most common population attributable risk associated with AF. However, treatment goals for blood pressure in AF remains undefined. The brachial blood pressure is recognised as an important predictor of future cardiovascular events. However, as compared to brachial, central blood pressure is more strongly related to CV outcomes. Aortic stiffness as a surrogate for persistently high central blood pressure, is of independent value in predicting AF outcomes. Further, certain anti-hypertensives can have a differential impact on brachial and central blood pressure. This may have important clinical implications in ongoing management of hypertension. However, further studies are required to demonstrate independent value of targeting central blood pressure to improve CV endpoints. This thesis evaluates the association of hypertension and aortic stiffness as a surrogate for central blood pressure with AF. Chapter 1 provides a comprehensive review of the literature linking hypertension (HTN) and AF. Additionally, a clinical assessment tool is proposed to better characterise atrial remodelling and end organ injury due to HTN. Pre-HTN is not benign and associated with increased risk of developing AF. Chapter-2 summarises the association of pre- HTN and new-onset AF by presenting the systematic review and meta-analysis of current published literature. Multiple studies have also reported the independent value of aortic stiffness in predicting CV and mortality outcomes. However, its association with new-onset AF is evolving. In Chapter 3, we present the systematic review and meta-analysis of all the published prospective trials associating increased aortic stiffness with AF, CV and all-cause mortality. Despite its adjunctive value, aortic stiffness assessment is sparingly used in clinical CV risk profiling. Chapter 4 summarises and critically appraises the methodology adapted by commercially available devices to evaluate central blood pressure indices and aortic stiffness to improve clinical integration of these tools in ongoing CV risk factor management in AF. However, none of these devices has been validated to assess central BP and aortic stiffness during AF. In Chapter 5, we present our findings of IMPULSE AF validation study (Trial Id: ACTRN12616001225404). It is the first study to evaluate non-invasive central blood pressure and aortic stiffness assessment during AF. We validated non-invasive CBP indices assessment by SphygmoCor against invasive aortic root pressure and reported reliable assessment of CBP indices and aortic stiffness during rate-controlled AF. Exaggerated BP response to exercise can unmask pre- HTN and has been associated with adverse CV outcomes. Chapter 6 characterises the difference of central and peripheral blood pressure indices response to exercise in our AF cohort. As compared to controls, AF patients were reported to have normal resting central BP indices. However, during exercise impaired conduit arterial compliance was found in AF patients. This may reflect a residual aortic stiffness associating AF with persistently high central BP. This thesis recognises the additional value of non-invasive central BP indices and aortic stiffness assessment to better characterise HTN and its associated end organ injury in AF. Our studies have expanded the scope of central pressure wave and velocity assessment in AF and during exercise. However, further work is needed to establish central blood pressure and aortic stiffness as a treatment target to prevent HTN induced CV events.