Novel Methods for Treating and Assessing Hypertension in Obstructive Sleep Apnoea

Abstract

In this thesis, the primary motivation was to develop a strategy to help improve the treatment of hypertension in patients with obstructive sleep apnoea (OSA), and to discover new biomarkers of risk that can be used for future prognostication and for therapeutic interventions. A central theme throughout is the emphasis on analysing and targeting the 24 hour blood pressure profile of patients with OSA, given our newer understanding that nocturnal blood pressure is the strongest predictor of cardiovascular mortality. Chapter 1 is a comprehensive literature review covering blood pressure physiology, the pathophysiology of hypertension and arterial stiffness both in non-OSA and OSA populations and treatment strategies including chronotherapy. In chapter 2 we explore the use of chronotherapy, or the altered timing of once-daily medication administration, in a randomised double blinded placebo controlled trial, in an effort to improve the blood pressure control of patients with OSA. In chapter 3, we explored 24 hour arterial haemodynamics in patients with OSA as a novel biomarker for future risk stratification and therapeutic interventions with the use of state-of-the-art technology. In the final chapter we summarise the key findings of our studies and briefly discuss future directions.