Blood Pressure Variability Following Acute Stroke: The Natural History, Definition and Measurement, and Prognostic Significance

Background: The complications following acute ischaemic stroke (AIS) are major contributors to morbidity and mortality when not appropriately managed. Whilst elevated blood pressure (BP) following a stroke requires urgent attention, increasing blood pressure variability (BPV) has been associated with poor neurological, functional and cognitive outcomes. However, there are reported inconsistencies in determining the clinical significance of BPV post-stroke. Furthermore, there is information lacking in understanding BPV definitions and measurement, natural history, and prognostic significance. Objectives: This thesis sought to investigate the methodologies of studies which have previously reported on the long-term outcomes (≥ 7 days) of BPV in acute stroke. Furthermore, in using prospectively collected multi-centre observational study data, this thesis describes the natural history of BPV and explores the prognostic significance following acute stroke. This work was completed using multiple BP devices and outcome data measured at various time points. Methods: In completing this thesis, the following were conducted: (i) a systematic review of studies reporting long-term outcome (≥1 week) of BPV following AIS, including methodologies and prognosis; (ii) a prospective multi-centre observational study comparing enhanced casual, continuous beat-to-beat, 24-hour and home BP measurement to define BPV in AIS; (iii) a prospective multi-centre observational study to determine the natural history and prognostic significance of BPV following AIS Results: The systematic review highlighted important methodological heterogeneity in quantifying and characterising BPV in AIS. It was determined the lack of descriptive reporting of studies investigating BPV in AIS contributed significantly to methodological heterogeneity. Furthermore, in this thesis, based on device failure rates, and participant acceptability and tolerance, we determined the most acceptable measurement technique in quantifying BPV is the enhanced casual. Additionally, variability data were summarised according to various definitions by measurement devices to observe the natural history, and this demonstrated significant differences by measurement device and definition. Moreover, functional outcome and cognitive impairment were assessed in relation to BPV at follow-up visits (1-, 3- and 12- months post-stroke). Increasing BPV was associated with short-term (1-month) poor functional and cognitive outcomes, and long-term functional outcome. Prognostic significance was reported using the enhanced casual and ambulatory devices.