Blood pressure variability : measurement and clinical implications

High blood pressure (BP), measured conventionally using clinic, ambulatory or home BP monitoring, is associated with target organ damage; however, the exact underlying mechanisms are not clear. A hypothesis which has gained wide acceptance during the last decade supports the notion that variability in BP (BPV) could provide important clinical information, over and above mean BP levels, and therefore could be relevant to the diagnosis and management of hypertension. Key gaps in the literature relating to BPV are that the prognostic significance of BPV as well as its impact on hypertension diagnosis and effect of treatment are unclear. The overall aims of this project were to investigate the effect of BPV on target organ damage in specific populations, to determine the impact of BPV on hypertension diagnosis, and to determine the effect of a novel intervention on BPV. Data supporting the notion that BPV may offer independent prognostic value are inconsistent, and this may be due to the wide variety of methodologies used for measuring BPV. BPV can be quantified from short-term BP monitoring (using 24-hour BP), mid-term BP (using home BP in the morning, evening or day-to-day) or long-term BP monitoring (using visit-to-visit clinic BP). Study 1 (chapter 1), aimed to examine the effect of BPV methodologies on the magnitude of BPV itself, as well as the effect of participant characteristics on BPV. Key methodological factors assessed were 1) the number of BP readings or visits used to quantify BPV and 2) the duration of BP monitoring. Following a scoping review process, data were extracted from 102 studies. The novel findings of this study were that the methodology used to quantify BPV, as well as age and mean BP level, affects the magnitude of BPV itself. This underscores the need to standardize BPV protocols, particularly regarding the number of BP readings and visits. Study 2 (chapter 2), aimed to determine the prognostic value of short-term BPV on organ damage related to retinal microvascular abnormalities in a post-hoc, hypothesis generating analysis among 35 non-diabetic and 28 patients with type II diabetes mellitus (T2DM). The novel findings of this study were that the BPV–related mechanisms underlying microvascular complications may differ between people with and without T2DM. Study 3 (chapter 3) sought to determine the prognostic value of short-term, mid-term and long-term BPV on organ damage related to heart structure and large artery stiffness in a follow-up study among 286 patients with uncomplicated hypertension and low to moderate cardiovascular risk. The important new findings were that changes in mean BP levels, but not BPV, were most relevant to changes in organ damage in patients with uncomplicated hypertension. Therefore, BPV appears to offer limited clinical utility in this patient population. Studies 4 and 5 aimed to determine the impact of within-visit BPV on hypertension diagnosis among adults (chapter 4), and children and adolescents (chapter 5), participating in the Australian Health Survey 2011-2013. Due to highly age-dependent reading-to-reading changes in BP, hypertension classification in adults varied according to the number of readings used for BP assessment (study 4). Moreover, the findings in study 5 showed that within-visit BP was highly variable in children and adolescents, with the magnitude of change being highly affected by BP level and age. The key finding from both studies was the significant impact of BPV on hypertension diagnosis, and this highlights the need for out-of-clinic BP measures to confirm diagnosis. Study 6 (chapter 6), aimed to determine the effect of vitamin D supplementation on long-term BPV, aortic stiffness, peripheral and central BP indices, among 241 individuals with vitamin D deficiency and knee osteoarthritis. The results showed that vitamin D supplementation did not improve long-term BPV, aortic stiffness or any other BP indices, in this patient population. Following on from this work we were invited to write an expanded review on the evidence from published randomised controlled trials regarding the effect of vitamin D supplementation on cardiovascular surrogate and hard clinical endpoints, including BPV (Appendix 4; study 7). This review concluded that vitamin D supplementation was ineffective for improving cardiovascular health among various patient populations, including the presence or absence of vitamin D deficiency. In summary, this PhD research program has made several novel observations. The methodology to quantify BPV can affect the magnitude of BPV itself and therefore BPV methodologies need to be standardized. Furthermore, the research has showed that short-term BPV may play a role in the pathophysiology of microvasculature in patients with T2DM; however, BPV (short-term, mid-term or long-term) did not offer additional prognostic value regarding organ damage (heart structure and large artery stiffness), over and above mean BP levels, among patients with uncomplicated hypertension and low to moderate cardiovascular risk. Additionally, within-visit BP was highly variable in adults as well as children and adolescents, implying that assessment and diagnosis of elevated BP should be confirmed using out-of-clinic BP monitoring. Finally, vitamin D was not effective in improving long-term BPV, large artery stiffness or other BP measures. Taken all together, this research provides novel data that significantly adds to the current knowledge body around BPV, by addressing key literature gaps related to the measurement and clinical implications of BPV.