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Title: Sources of variation in human blood pressure control
Author: Taylor, Chloe Eleanor
Awarding Body: Liverpool John Moores University
Current Institution: Liverpool John Moores University
Date of Award: 2011
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The control of blood pressure plays a vital part in homeostasis in humans. Poor regulation of blood pressure has been associated with an increased risk of events such as myocardial infarction, sudden cardiac death, and stroke. The studies in this thesis are designed to explore sources of variation in human BP control, and in particular to examine the interactions between BP status, activity and circadian variation. In study 1 the association between BP status and the acute exercise-mediated change in BP was investigated. A total of 32 participants, with pre-exercise MAP of 65-110mm Hg, cycled for 30 min at 70% peak oxygen uptake. Systolic and diastolic BP were measured (Portapres) before exercise and for 20 min after exercise. Changes in BP were regressed against pre-exercise values, and against the mean of pre- and post-exercise BP, an index known not to be prone to the influence of mathematical coupling and regression-to-the-mean artefacts. Correlations between pre-exercise BP and the exercise-mediated reductions were typical of those previously reported (r = 0.37-0.62, P < 0.05). Artefact-free indices of BP status (pre- and post-exercise mean) did not correlate with reductions in BP (P > 0.05), which were moderated more by maximal oxygen uptake and time of day (P < 0.05). These data indicate that, if statistical artefacts are not controlled for, the influence of BP status on the degree of PEH can be spuriously exaggerated to the extent that other more important moderators of BP change are masked. In study 2 meta-analytical methods were used to enhance the statistical power and precision with which to explore the association between BP status and exercise-mediated changes in ambulatory BP. Studies entered into the meta-analysis were required to meet inclusion criteria of ambulatory monitoring following exercise and comparisons to a control condition to minimize regression-to-the-mean artefacts. Blood pressure status was a significant moderator of PEH indicating that hypertensive patients will benefit from greater reductions in BP. Age, BMI and V02max were also identified as significant moderators PEH, indicating that older individuals with larger BMIs and lower fitness levels will benefit most from exercise. Pooled mean changes (95%CI) in daytime and nocturnal SBP were -3.8 (-5.4 to -2.3) and -3.0 (-4.7 to -1.3), respectively, and may be deemed as clinically significant reductions. Future meta-analyses should investigate the effects of chronic exercise on ambulatory BP and its cardioprotective effects. In study 3 the acute effects of PA on BP and symptoms of OSA were examined using blood pressure reactivity profiles during sleep and following waking. Ambulatory BP and actigraphy data were collected between 20:00-10:00h in 11 OSA patients and 18 healthy controls. Blood pressure reactivity indices were calculated (Jones et al., 2009) and compared between groups and over time using general linear models. The greatest mean (SD) systolic BP reactivity in the healthy controls was 15.4 (42.7) mmHg/activity count, occurring 0-2 hours after waking, whereas the peak systolic BP reactivity of 12.7(14.4) mmHg/activity count occurred during sleep in OSA patients (P < 0.05). This evidence of diminished nocturnal blood pressure control in response to activity may be associated with the peak incidence of MI in OSA, which occurs between 00:00 and 06:00 h (Kuniyoshi et al., 2008). In study 4 the focus moved from acute activity to chronic, with an investigation of leisure-time physical activity in OSA patients, in which the relationships with BP, OSA severity and daytime sleepiness were examined. Levels of leisure-time physical activity, estimated with self-reported activity questionnaires, were not significantly different between OSA patients (n=96) and a healthy control group (n=118). Compared with healthy controls, OSA patients displayed higher SBP, DBP and MAP (P < 0.05), but physical activity had no effect on BP in either group when adjusted for age and gender (P > 0.05). However, leisure-time physical activity was associated with reduced ODI and daytime sleepiness (Epworth Sleepiness Scale) in OSA patients (P < 0.05). The differences in daytime sleepiness between the lowest and highest activity groups were comparable to the reductions found with CPAP treatment. Physical activity would provide a useful treatment for OSA patients, potentially as an adjunct to traditional CPAP therapy. In study 5 the contribution of the mechanical and neural components of the cardiac baroreflex to diurnal variation in BP control were investigated. In 12 healthy participants, the modified Oxford method was used to quantify baroreflex gain for rising (Gup) and falling (Gdown) pressures in the morning (0700h) and afternoon (1600h). A novel analysis method based on linear mixed models (Atkinson et al., 2010) was employed to compare the integrated, mechanical and neural gains between the two times of day. There was significant diurnal variation in integrated gain, with an attenuated response in the morning (Gup= 13.0 ± 0.6; Gdown= 6.3 ± OA ms/mm Hg) when compared with the afternoon (Gup= 15.1 ± 0.6; Gdown= 12.6 ± OA ms/mm Hg). For rising pressures the diminished integrated gain in the morning was caused by a reduction in mechanical gain, whereas for falling pressures it was caused by a reduction in neural gain. It is proposed that the high prevalence of cardiovascular events in the morning is due to diminished mechanical transduction of pressure into arterial distension at this time. In study 6 postural influences on diurnal variation in cardiac baroreflex sensitivity were investigated, and the contribution of mechanical and neural baroreflex components were determined. Integrated baroreflex sensitivity was reduced in the morning and afternoon when an upright posture was assumed, and was primarily attributed to decreases in neural gain. Although observed at both times of day, reductions in baroreflex sensitivity due to the change in posture occurred to a greater extent in the afternoon. This caused the diurnal variation that was reported in the supine position to be attenuated for rising BP, and eliminated entirely for falling BP when participants changed to a standing position. The studies in this thesis have provided further knowledge and understanding of sources of variation in human BP control, including the effects of BP status, health status, fitness, physical activity, diurnal variation and postural changes. Methodological issues in BP research, clinical applications, and mechanisms responsible for BP regulation have also been addressed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC1200 Sports Medicine