<strong>Background:</strong> Stroke is a leading cause of disability and premature death in China and blood pressure is widely considered to be a major cause. Despite this, substantial uncertainty remains about the shape and strength of the association between blood pressure and stroke pathological types in China. <strong>Methods:</strong> Information from the China Kadoorie Biobank study (a prospective cohort study of 0.5 million men and women in China recruited during 2004-8) was used to relate usual blood pressure to risk of stroke, by stroke pathological type (cerebral infarction [ischaemic stroke], intracerebral haemorrhage and subarachnoid haemorrhage). Prospective analyses excluded participants with a history of vascular disease recorded at baseline; involved correction for regression dilution bias; used incident stroke events for which the diagnosis involved a head CT or MRI scan; and, assessed for confounding and effect modification by major vascular risk factors. These prospective analyses were informed by a set of prior analyses, including: a description of baseline associations between blood pressure and other vascular risk factors, to identify potential confounders; analyses of resurvey blood pressure data from ~20_000 participants, to assess regression dilution bias; and analyses of stroke follow-up data, involving an adjudication ‘sub-study’ performed specifically as part of this thesis, to evaluate the diagnostic accuracy of incident stroke events (~1000 events were adjudicated). <strong>Results:</strong> During 2.1 million person-years at risk, there were 5783 incident stroke events. At ages 40-79 years, the proportional difference in risk of both cerebral infarction and intracerebral haemorrhage associated with a given absolute difference in usual blood pressure was constant throughout the range of blood pressures examined (SBP 120-170 mm Hg, DBP 70-100 mm Hg). Overall, the strength of association was approximately 1.5-times greater for intracerebral haemorrhage than for the other stroke pathological types: 10 mm Hg higher usual SBP was associated with 82% (95% CI: 76%-89%) higher risk of intracerebral haemorrhage, 47% (44%- 50%) higher risk of cerebral infarction and 52% (35%-71%) higher risk of subarachnoid haemorrhage (the overall mean age at event for each stroke pathological type was ~60 years). For both cerebral infarction and intracerebral haemorrhage, there was strong evidence of major effect modification by age and to a lesser extent by a number of other vascular risk factors. The associations by age were around a third as extreme at age 70-79 years than at 40-49 years. The annual absolute differences in risk associated with a given absolute increase in usual blood pressure, however, were greater at older age. <strong>Conclusions:</strong> In Chinese adults, usual blood pressure was strongly and positively related to risk of all stroke pathological types. The strength of association was greater for intracerebral haemorrhage than other stroke pathological types. For both cerebral infarction and intracerebral haemorrhage, there was evidence of major effect modification by age. The overall effect of blood pressure on stroke risk was much greater than estimated by previous prospective studies in China, particularly for intracerebral haemorrhage.

Visit-to-visit variability in blood pressure (BP) increases stroke risk, independent of mean BP. However, its physiological validity, the ideal method of measurement and the mechanisms increasing cardiovascular risk are unclear. In meta-analyses of individual patient data, I pooled associations between BP variability and risk of stroke, all cardiovascular events and death. I then determined antihypertensive drug-class differences in cardiovascular risk, intra-individual (I-VR) and inter-individual BP variability (M-VR). In 500 Oxford Vascular Study (OXVASC) patients undergoing thrice-daily home (HBPM) and awake ambulatory monitoring (ABPM), associations between mean, maximum or variability in BP (CV-BP) were determined with premorbid BP, hypertensive arteriopathy (creatinine, aortic stiffness, cognitive impairment, stroke versus TIA and leukoaraiosis) and cardiovascular events. In 200 patients, I determined associations with pulsatility or stiffness (pulse wave velocity) in cerebral and aortic vessels. There was a 21% and 27% increased risk of stroke and myocardial infarction per standard deviation of CV-SBP in 318700 patients, independent of mean SBP. In 244,479 patients, SBP variability was reduced by CCBs and diuretics within (I-VR=0.89, 95% CI=0.82-0.96, p=0.0001) and between individuals (M-VR 0.83, 0.77-0.89, p<0.0001), especially in the first year of treatment, explaining drug class differences in stroke risk (OR=0.76, 0.68-0.87, p<0.0001). In OXVASC, drug class differences on day-to-day SBP variability were greatest immediately after waking. Residual hypertension after treatment on HBPM but not ABPM (BP>135/85) predicted recurrent cardiovascular events (HR 2.82, 1.44-5.51, p=0.002 vs. 1.48, 0.68-3.23, p=0.33), reflecting stronger associations with premorbid BP and hypertensive arteriopathy, due largely to inaccuracy of ABPM in patients aged >65 years. Furthermore, day-to-day maximum and CV-SBP were associated with premorbid BP, hypertensive arteriopathy and cardiovascular events, with no additional predictive value of mean SBP when analysed with maximum SBP. Maximum SBP was greater in men and CV-SBP in women, whilst age and creatinine determined both. Increased stroke risk may partly be due to the association between BP variability and cerebral pulsatility, which was correlated with leukoaraiosis (p=0.01) and determined by aortic stiffness (p=0.016) and pulsatility (p<0.001). BP variability is clinically significant and physiologically valid, and is treatable with CCBs and diuretics. After TIA or minor stroke, HBPM best identifies residual hypertension and demonstrates the predictive value of BP variability and maximum BP, but associated arterial changes might explain some of the increased stroke risk.

Intradialytic Hypotension (IDH) is the commonest complication of maintenance haemodialysis and is associated with increased morbidity and mortality. However, there is no standardised definition of IDH, making comparisons between studies difficult. This observational study with a total of 80 patients and over 600 dialysis sessions showed a poor correlation between symptoms and hypotension. Importantly, patients experienced low blood pressure without symptoms, so continuous intradialytic blood pressure monitoring is required to identify this asymptomatic group. In light of these findings, a revised definition of IDH is suggested. This study also aimed to identify predictors of IDH that could be detected in sufficient time to allow a mitigating intervention. A novel non-invasive alternative for continuous blood pressure monitoring is introduced which uses intra-fistula pressure data from the sensors sited in the extracorporeal circuit of the dialysis machine. Results show that in the majority of patients, changes in intra-fistula pressure correlate with blood pressure measurements obtained by a standard oscillometric device. To investigate whether IDH can be predicted, a photoplethysmogram (PPG) waveform was obtained from a pulse oximeter attached to the finger or ear. Continuous PPG monitoring of patients with IDH during dialysis demonstrated that some IDH episodes were predictable using the variation in the PPG baseline with respiration as a surrogate for low blood volume. Additionally, the area under the curve of the PPG waveform can be used as a surrogate for cardiac output and peripheral vascular tone, resulting in a reasonable predictor for potentially critical changes in blood pressure during dialysis. Individually, the novel metrics described here are limited in their identification of IDH in all patients affected, but in combination they may be used to develop a multi-parameter predictive model. The relative merits of personalised versus population-based models are explored and a conclusion is drawn that personalised multi-parameter data fusion modelling for haemodialysis patients would be an important area for future work.

Research suggests hypertension is associated with reduced somatosensory perception. Further, natural fluctuations in blood pressure (BP) across the cardiac cycle have been shown to modulate nociceptive responding, pain and tactile sensitivity, suggesting that arterial baroreceptors may be important moderators of somatosensation. This thesis further examined the influence of natural fluctuations in BP, and thus baroreceptor activity, across the cardiac cycle on electrocutaneous pain and tactile sensory thresholds and pain-related evoked potentials (PREPs) in normotensive individuals. Study 1 found pain thresholds were higher, i.e. pain was reduced, during systole compared to diastole. Further analysis revealed only participants with low-normal systolic BP displayed this cardiac cycle modulation, suggesting tonic BP may moderate cardiac cycle-related pain modulation. In the second study, tactile sensory thresholds did not vary across the cardiac cycle. However, when participants were split into high-normal and low-normal BP groups, interactions between BP and tactile sensory thresholds across the cardiac cycle were revealed. This finding suggests tonic BP may be an important factor determining the cardiac cycle modulation of tactile sensation. Study 3 found no variation in the N2 or P2 peak amplitudes, or N2-P2 peak-to-peak amplitudes across the cardiac cycle at scalp recording sites Cz, C3, or C4. Furthermore, BP median split analyses revealed no BP Group or interaction effect. As previous work reported a systolic dampening of PREPs, these data suggest the cardiac cycle-related modulation of PREPs may not be as robust as other measures of pain such as the nociceptive flexion reflex. Study 4 reported, in line with Study 3, no cardiac cycle related modulation of PREPs following stimulation of the right and left hands. However, a Hand x Scalp Electrode Site x Interval interaction was revealed for N2 peak amplitudes. These data suggest that the combination of side of stimulation and scalp recording site may be important in determining the patterning of PREPs across the cardiac cycle. Taken together, the findings of these studies suggest that pain perception, and to a lesser extent tactile sensation, are influenced by natural variations in BP across the cardiac cycle. However, modulation appears dependent on tonic BP. Conversely, pain-related brain activity across the cardiac cycle was not affected by tonic BP, but may be influenced by the combination of stimulation and recording sites.

Hypertension is the leading cause of cardiovascular diseases worldwide. There is evidence of the rising incidence and prevalence of chronic diseases of lifestyle in developing countries. Physical activity has been regarded as a commonly accepted modality for treating hypertension. The aim of this study was to determine if physical activity levels are associated with hypertension among employees of Kigali Institute Science and Technology in Kigali,Rwanda. A quantitative, cross- sectional design was used and all staff members (325 employees) of Kigali Institute of Science and Technology (KIST) represented the study population. Random sampling was used to determine the study sample. Data was collected by means of a self-administered questionnaire adopted from The International Physical Activity Questionnaire (IPAQ).Data analysis was done using Statistical Package for Social Sciences (SPSS) software version 15.0. Descriptive statistics using frequencies, percentages, means, and standard deviations and inferential statistics using Chi-square tests were employed. The data were presented with use tables,figures,graphs, and pie charts. Ethical issues including obtaining permission for conducting the study, informe consent,anonymity,confidentiality, voluntary participation, and the right to withdraw from the study was observed in this study. The study found a prevalence of 34% participants with hypertension. The prevalence of hypertension was associated with age, smoking, drinking alcohol, suffering for diabetes mellitus, and body mass index (BMI). Over one-fifth of the participants in the physically active group were hypertensive while 68% of the participants in the physically inactive group were hypertensive. This study shows that hypertension status is strongly associated with physical activity levels [X² = 20.381 with (P<0.001)]. The study further showed that smoking and suffering from diabetes mellitus were also associated with levels of physical activity (P = 0.003 and p = 0.004 respectively). The current study concludes that physical activity is needed for employees at Kigali Institute of Science and Technology as part of preventive measures for chronic diseases of lifestyle. Therefore, the recommendations were proposed to various categories of people and stakeholders to be actively involved in the promotion of physical activity among employees of Kigali Universities in Rwanda. / Magister Scientiae (Physiotherapy) - MSc(Physio)

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Well-established risk factors for CVD include increasing age, male sex, sedentary lifestyle, obesity, smoking, diabetes, hypertension, dyslipidaemia and low socio-economic status. Traditional risk factors do, however, not fully explain cardiovascular risk in general. In this thesis we focused on two conventional risk factors (smoking, blood pressure), and two unconventional risk markers (adiponectin, an adipocyte derived protein; and sialic acid (SA), a marker of systemic inflammation) for prediction of CVD events. Aims: In Paper I we examined to what degree smoking habits modify the risk of CVD in relation to systolic blood pressure levels in middle-aged men. In Paper II we investigated the predictive role of adiponectin for risk of CVD as well as the cross-sectional associations between adiponectin and markers of glucose metabolism, also in men. In Paper III we examined if increasing pulse pressure (PP) and increasing levels of SA both increase the risk of CVD and whether their effects act in synergism. In Paper IV the association of SA with risk of incident diabetes mellitus and related complications, resulting in hospitalization, was studied. Subjects and Methods: Two large-scale, population-based, screening studies with long follow-up periods have been used. The Malmö Preventive Project (MPP) was used with 22,444 individuals in Paper I and a sub cohort of 3,885 individuals in Paper II. The Värmland Health Survey (VHS) was used in Papers III and IV with 37,843 and 87,035 individuals, respectively. Results: CVD risk increases with increasing systolic blood pressure levels and this risk is almost doubled in smokers. Total adiponectin level is not associated with increased risk of future CVD but it is inversely associated with markers of glucose metabolism. PP and SA both contribute to risk of future CVD. Adjustment for mean arterial pressure reduces the risk induced by PP. Elevated SA contributes to increased risk of incident diabetes and related complications leading to hospitalization.

Thesis (M Sport Sc (Sport Science))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: It is well-known that acute and chronic aerobic and resistance exercise results in decreased blood pressure (BP) in hypertensive individuals. There is little evidence that water exercise has a similar effect on BP response. There is also no certainty regarding the magnitude and duration of post exercise hypotension (PEH) after either land or water-based exercise. Most studies were also performed under controlled laboratory conditions and very few characterised the PEH response under real life conditions. The current study endeavoured to examine the magnitude and duration of PEH after an acute session of water- and land-based exercise during free living conditions in persons with mild to moderate hypertension. Twenty-one men and women (aged 52 ± 10 years) volunteered for the study. All participants were pre-hypertensive or hypertensive. Participants completed a no exercise control session, a water exercise session and a combined aerobic and resistance land exercise session in random order. After all three sessions, participants underwent 24 hour monitoring using an Ergoscan ambulatory BP monitoring device. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were monitored to determine changes from resting values after each session and to compare the PEH responses between land and water exercise. Overall, the land exercise treatment caused a 3.6 mmHg lower average SBP over 24 hours than the control treatment (P = 0.04). The average difference over 24 hours between the water and control treatments was 2.2 mmHg and between land and water exercise it was 1.5 mmHg (P > 0.05). During daytime, both land and water exercise resulted in significantly lower SBP (12.7 and 11.3 mmHg) compared to the control session (2.3 mmHg). The PEH response lasted for 24 hours after land exercise and nine hours after water exercise. There was no difference in the daytime DBP for the three treatments (P > 0.05). Although all three groups showed significant reductions during night time, both exercise treatments showed greater nocturnal falls in SBP, DBP and MAP than the control treatment. / AFRIKAANSE OPSOMMING: Dit is alombekend dat akute en chroniese aërobiese- en weerstandsoefening tot ‘n afname in bloeddruk (BD) lei in persone met hipertensie. Daar is egter min getuienis dat wateroefening dieselfde effek op die bloeddruk respons het. Daar is ook nie sekerheid oor die grootte en duur van post-oefening hipotensie na water- of landoefening nie. Die meeste studies is onder gekontrolleerde laboratorium omstandighede gedoen en min resultate is beskikbaar onder alledaagse lewensomstandighede. Die huidige studie het gepoog om die grootte en duur van die post-oefening hipotensie respons in persone met ligte tot matige hipertensie onder alledaagse omstandighede na ‘n akute sessie van water- en landgebaseerde oefening te ondersoek. Een-en-twintig mans en vrouens (ouderdom 52 ± 10 jaar) het ingewillig om aan die studie deel te neem. Alle deelnemers was hipertensief of pre-hipertensief. Alle deelnemers het ‘n kontrolesessie, ‘n wateroefeningsessie en ‘n gekombineerde aërobiese en weerstands landoefensessie, in lukrake volgorde, voltooi. Na elke sessie het die deelnemers 24 uur bloeddrukmonitering met ‘n Ergoscan wandelende bloeddruk monitor ondergaan. Sistoliese bloeddruk (SBD), diastoliese bloeddruk (DBD), gemiddelde arteriële bloeddruk en harttempo (HT) is gemonitor om die veranderinge vanaf rustende waardes na elke sessie te bepaal en om die hipotensiewe respons na land- en wateroefening te vergelyk. Landoefening het ‘n 3.6 mmHg laer gemiddelde SBD oor 24 uur tot gevolg gehad in vergelyking met die kontrolesessie (P = 0.04). Die gemiddelde verskil oor 24 uur tussen die water- en kontrolesessies was 2.2 mmHg en 1.5 mmHg tussen die land en water oefensessies (P > 0.05). Gedurende die dag het beide die land- and wateroefening gelei tot beduidende laer SBD (12.7 en 11.3 mmHg) in vergelyking met die kontrolesessie (2.3 mmHg). Die post-oefening hipotensie het 24 uur geduur na die landoefening en nege uur na die wateroefening. Daar was geen verskil in DBD gedurende die dag tussen die drie groepe nie (P > 0.05).

Μια συσκευή για τη μέτρηση της πίεσης του αίματος ενός ασθενή, περιλαμβάνει έναν επεξεργαστή προσκολλημένο σε μια συσκευή εισόδου, ο οποίος δέχεται μια αρχική είσοδο, που αντιπροσωπεύει την απόλυτη πίεση του αίματος του ασθενή και ένα μη-επεμβατικό αισθητήρα, που ακουμπάει τον ασθενή για τη μέτρηση τουλάχιστον μιας ‘φυσιολογικής’ λειτουργίας. Ο επεξεργαστής εκτελεί μια διαδικασία για την εκτίμηση της αρχικής εισόδου και της ‘φυσιολογικής’ λειτουργίας, για να υπολογίσει την πίεση του αίματος του ασθενή. Μια μέθοδος για τον υπολογισμό της πίεσης του αίματος ενός ασθενή, περιλαμβάνει τα βήματα της αποθήκευσης της αρχικής εισόδου, που αντιπροσωπεύει την απόλυτη πίεση του αίματος του ασθενή, της μη-επεμβατικής ‘αίσθησης’ (μέσω αισθητήρα) τουλάχιστον μιας ‘φυσιολογικής’ λειτουργίας και της εκτίμησης των δύω τιμών για τον υπολογισμό της πίεσης του αίματος. Η παρούσα εργασία μπορεί επίσης να χρησιμοποιηθεί για την ανάλυση και τον εντοπισμό άλλων ‘φυσιολογικών’ μεταβλητών όπως της ενδοτικότητας των τοιχωμάτων των αγγείων, των αλλαγών στην ένταση των κοιλιακών συστολών, των αλλαγών στην αγγειακή αντίσταση, των αλλαγών στον όγκο των υγρών, των αλλαγών στον καρδιακό παλμό, της συσταλτικότητας του μυοκαρδίου και άλλων σχετικών παραγόντων. / This dissertation refers to a device for non-invasively measuring the blood pressure of a patient. Such a device consists of a processor attached to an input device, which receives an initial input value, representing the patient’s absolute pressure, and a non-invasive sensor attached to the patient for measuring at least one physiological function. For determining the patient’s blood pressure, the processor performs a process for evaluating the initial input and the physiological function of the sensor. A method for non-invasively measuring a patient’s blood pressure includes, firstly, storing the initial input (which represents the patient’s absolute pressure), secondly, non-invasively sensing at least one physiological function and, finally, evaluating both these inputs for measuring the patient’s blood pressure. This dissertation can also be used for the analysis of other physiological variables such as vascular wall compliance, changes in the strength of ventricular contractions, alterations in fluid volume or in cardiac output and other related factors.

Diabetes mellitus is a group of metabolic disorders caused by a relative or absolute lack of insulin. Currently, 23.6 million Americans have diabetes. Diabetes can lead to serious microvascular and macrovascular complications, such as cardiovascular disease, blindness, kidney disease, lower-limb amputations, and premature death. Due to the potential cardiovascular complications and the high prevalence of co-morbid hypertension and/or hyperlipidemia in patients with diabetes, diabetes management should include close monitoring of blood glucose, blood pressure, and cholesterol levels. Medical management of diabetic patients is costly; approximately 1 in every 10 health care dollars is currently spent treating diabetes. Studies have shown that in chronic conditions such as diabetes, increased medication use results in demonstrable improvements in health outcomes, reduced hospitalization rates, and decreased direct health care costs. To date no studies have evaluated the impact of a pharmacist-led intervention on diabetic medication adherence. The purpose of this investigation was to analyze the impact of a pharmacist-led medication management program on medication adherence and pharmacy costs and to evaluate clinical measures of diabetes, hypertension, and hyperlipidemia. This study was a quasi-experimental, longitudinal, pre-post study, with a control group. Scott & White Health Plan (SWHP) patients with diabetes (type 1 or type 2), poor glycemic control (most recent A1C >7.5%), and living within 30 miles of participating pharmacies were invited to participate in the intervention which consisted of monthly appointments with a clinical pharmacist and a co-payment waiver for all diabetes medications and testing supplies. A total of 118 patients met study inclusion criteria and were enrolled in the intervention between August 2006 and July 2008. Intervention patients were matched on sex and age to SWHP patients with poor diabetes control living more than 30 miles from a participating pharmacy. To measure the impact of the intervention, medical and pharmacy data were evaluated for one year before and after the study enrollment date. A significant difference was seen in the percentage of patients with type 1 diabetes in the intervention group (14) and the control group (3). The medication management program significantly improved A1C levels in intervention patients relative to controls (-1.1% vs. 0.6%) and was more effective in lowering A1Cs in type 2 diabetics than type 1 patients. Although the generalized linear model did not show that the intervention significantly improved the percentage of patients achieving the ADA goal A1C of <7% compared to controls, the multivariate logistic regression, which controlled for factors such as diabetes type, showed that patients participating in the intervention were 8.7 times more likely to achieve the A1C goal. Persistence with diabetic medications and the number of medications taken significantly increased in the intervention group; however, adherence rates, as measured by medication possession ratio (MPR), did not significantly improve relative to controls. The expenditure on diabetic medications and testing supplies increased substantially more in the intervention group than in the control group. The percentage of patients adherent with antihypertensive medications (MPR ≥80%) increased from 76% to 91% in the intervention group and decreased from 68% to 63% in the control group (P<0.05); no significant difference in blood pressure control was observed. For hyperlipidemia medications, adherence and persistence increased and pharmacy costs decreased in both groups, likely due to the introduction of the first generic HMG-CoA reductase inhibitor into the market during the study period. Future research is needed on the impact of the intervention on medical resource utilization and costs. / text

Leptin is an adipokine that acts centrally to regulate feeding behaviour, energy expenditure and autonomic function via activation of its receptor (ObRb) in nuclei in the central nervous system (CNS). This thesis investigates the involvement of two sensory circumventricular organs (CVOs), the subfornical organ (SFO) and area postrema (AP), in mediating the central effects of leptin using a variety of experimental approaches. We first show that acute electrical stimulation of the SFO elicits feeding in satiated rats, supporting a role for this specialized CNS structure in the control of food intake. We then demonstrate, using RT-PCR, the presence of ObRb mRNA in SFO and, using whole cell current clamp electrophysiology, reveal that leptin influences the excitability of individual SFO neurons, causing both excitatory and inhibitory responses. Furthermore, we find that leptin activates the same SFO neurons activated by amylin. Given the association between obesity and hypertension and the well-established role of the SFO in cardiovascular regulation, we show that leptin microinjection into the SFO decreases blood pressure in young rats, effects that are abolished in leptin-resistant, diet induced obese rats, suggesting that leptin-insensitivity in the SFO of obese, leptin-resistant, individuals may contribute to obesity-related hypertension. Our studies also show that the medullary AP expresses ObRb and that leptin influences the excitability of AP neurons. Furthermore, we show that leptin and amylin act on the same subpopulation of neurons in the AP. Finally, our preliminary AP/SFO lesion studies reveal that animals with these lesions exhibit a profound decrease in body weight and food intake and no longer exhibit decreases in body weight in response to peripheral leptin administration. In summary, the data presented in this thesis suggest the SFO and AP to be important in body weight homeostasis and in mediating the central effects of leptin. In addition, these areas appear to be important in the integration of multiple signals derived from peripheral sources. Furthermore, the fact that the SFO appears to be involved in leptin effects on both energy balance and cardiovascular regulation attest to the integrative nature of the SFO in the control of diverse physiological functions. / Thesis (Ph.D, Physiology) -- Queen's University, 2012-10-15 14:57:15.387