High blood pressure is a major public health issue. However, there are many physical and non-physical factors that affect the measurement of blood pressure (BP) over very short time spans. Therefore, it is very difficult to write a mathematical equation which includes all relevant factors needed to estimate accurate BP values. As a result, a possible solution to overcome these limitations is the use of an artificial neural network (ANN). The aim of this research is to design and implement a new ANN approach, which correlates the arterial pulse waveform shape to BP values, for estimation of BP in a single heartbeat. To test the feasibility of this approach, a pilot study was performed on an arterial pulse waveform dataset obtained from 11 patients with normal BP and 11 patients with hypertension. It was found that the proposed method can accurately estimate BP in single heartbeats and satisfy the requirements of the ANSI/AAMI standard for non-invasive measurement of BP.

When it comes to monitoring human health, accuracy is not a choice. Accuracy in blood pressure (BP) estimation is essential for proper diagnosis and management of hypertension. An error of 5 mmHg is so serious, it can be responsible for doubling or halving number of patients diagnosed with hypertension. Motion artifacts are external sources of inaccuracy and can be due to sudden arm motion, muscle tremor, shivering, and transport vehicle vibration. Medium term drift, due to changing environmental factors, such as ambient temperature, can also contribute to the inaccuracy. Long term drift (ageing), can reach 9 mmHg during the first three months of usage. In this thesis, a new stage is added to current cuff based BP devices. This stage is responsible for adjusting the pressure reading before displaying it to end users. The proposed stage is provided with a 3-axis accelerometer, which makes the detection of motion artifacts during measurement possible. Moreover, it monitors changes in the ambient temperature and sensor ageing, so that it will adaptively compensate for these inaccuracies. These sources of inaccuracy are suppressed using algorithms based on Empirical Mode Decomposition (EMD), which has the feature of removing unwanted noise components little effect on the phase or the frequency distribution of the measured signal. With motion artifacts, measurements show that the proposed algorithms considerably improved the accuracy of the blood pressure estimates in comparison with the commonly-used conventional oscillometric algorithm that does not include a stage for artifact suppression, and allowed the estimates to consistent with the international ANSI/AAMI/ISO standard. Moreover, simulations based on experimental results show that the system is able to compensate for drift due to temperature changes and ageing with excellent performance. Results show promise towards building a robust BP monitor, with very low errors due to motion artifacts, environmental changes, and ageing.

Increased arterial stiffness is a predictor of cardiovascular events and mortality across a diverse range of populations. Although gross-mechanical stiffness can be measured in vivo, in order to understand the pathological mechanisms it will be necessary to identify which local micro-structural remodelling events are the prime drivers of altered macro-mechanical function. However, characterisation of arterial structure by conventional histological approaches: i) commonly induces artefacts as a consequence of the sectioning process, ii) provides no insight into the three dimensional structure of the tissue and iii) is performed on unpressurised tissue. This project has set out to address these limitations by developing new micro computed x-ray tomography (micro-CT) methodologies which are capable of visualising the three dimensional structure of rat arteries. This new methodology was then been applied in combination with gross-and micro-mechanical testing and atomic force microscopy imaging to characterise the effects of both intra-luminal pressure and age on arterial structure and function. From these investigations it was clear that micro-CT could readily distinguish discrete tissue sub-structures in paraffin embedded tissues, including skin and arteries and that this imaging approach was compatible with complimentary histological and immunohistochemical analyses. Characterisation of the structure and mechanical function of carotid arteries in aged rats demonstrated localised stiffening in the adventitial layer and a change in the molecular structure of adventitial collagen. The effects of intra-luminal pressure on structure using micro-CT revealed changes in artery cross-sectional area, which suggest the artery wall may be compressible. Investigations into the effects of pressure on the molecular structure of adventitial collagen revealed an increase in periodicity at mean pressure. These findings together demonstrate that the adventitial layer has an important role in the development of arterial stiffness. Micro-CT can reveal novel information that improves our understating of artery structure and how artery structure changes during ageing.

The purpose of the study was to examine psychological and methodological factors which would predict the white coat effect (WCE). The WCE is defined as the difference (mm Hg) between ambulatory and office measured blood pressure (BP). Sixty three community volunteers participated in this study. Participants were divided into 3 Response style groups: (1) Office responders had ambulatory BP values which were lower than office BP, (2) Non responders showed a minimal difference between office and ambulatory BP, and (3) Home responders had significantly higher ambulatory BP compared to office BP. Participants were asked to have a series of BP readings taken by a physician, nurse and by themselves and participate in 24 hour ambulatory monitoring. State and trait self-report psychological measures were completed. Self measured BP was the most representative of ambulatory BP for the sample as a whole, and in particular for the Home responders. State anxiety, previously dismissed as mediating factor in the expression of the white coat effect, proved to discriminate between the groups. Office responders had significantly higher levels of state anxiety, directly related to BP measurements, compared to Home and Non responders. Habituation to the experience of having BP measured by a physician, and habituation of the anxiety prior to the BP measurement, was different among the three groups. Trait psychological variables did not distinguish group membership. Self measured systolic BP, state anxiety prior to self measured BP, habituation to physician measured BP and the anxiety preceding it, were entered as predictors variables in a discriminant function analyses. These variables were able to correctly classify group membership for 63% of the sample. / Arts, Faculty of / Psychology, Department of / Graduate

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Hypertension, a major risk factor in the cardiovascular system, is characterized by an increase in the arterial blood pressure. High dietary sodium is linked to multiple cardiovascular disorders including hypertension. Salt sensitivity, a measure of how the blood pressure responds to salt intake is observed in more than 50% of the hypertension cases. Nitric Oxide (NO), as an endogenous vasodilator serves many important biological roles in the cardiovascular physiology including blood pressure regulation. The physiological concentrations for NO bioactivity are reported to be in 0-500 nM range. Notably, the vascular response to NO is highly regulated within a small concentration spectrum. Hence, much uncertainty surrounds how NO modulates diverse signaling mechanisms to initiate vascular relaxation and alleviate hypertension. Regulating the availability of NO in the vasculature has demonstrated vasoprotective effects. In addition, modulating the NO release by different means has proved to restore endothelial function. In this study we addressed parameters that regulated NO release in the vasculature, in physiology and pathophysiology such as salt sensitive hypertension. We showed that, in the rat mesenteric arterioles, Ca2+ induced rapid relaxation (time constants 20.8 ± 2.2 sec) followed with a much slower constriction after subsequent removal of the stimulus (time constants 104.8 ± 10.0 sec). An interesting observation was that a fourfold increase in the Ca2+ frequency improved the efficacy of arteriolar relaxation by 61.1%. Our results suggested that, Ca2+ frequency-dependent transient release of NO from the endothelium carried encoded information; which could be translated into different steady state vascular tone. Further, Agmatine, a metabolite of L-arginine, as a ligand, was observed to relax the mesenteric arterioles. These relaxations were NO-dependent and occurred via α-2 receptor activity. The observed potency of agmatine (EC50, 138.7 ± 12.1 µM; n=22), was 40 fold higher than L-arginine itself (EC50, 18.3 ± 1.3 mM; n = 5). This suggested us to propose alternative parallel mechanism for L-arginine mediated vascular relaxation via arginine decarboxylase activity. In addition, the biomechanics of rat mesentery is important in regulation of vascular tone. We developed 2D finite element models that described the vascular mechanics of rat mesentery. With an inverse estimation approach, we identified the elasticity parameters characterizing alterations in normotensive and hypertensive Dahl rats. Our efforts were towards guiding current studies that optimized cardiovascular intervention and assisted in the development of new therapeutic strategies. These observations may have significant implications towards alternatives to present methods for NO delivery as a therapeutic target. Our work shall prove to be beneficial in assisting the delivery of NO in the vasculature thus minimizing the cardiovascular risk in handling abnormalities, such as hypertension.

Trata-se de um estudo descritivo transversal de abordagem quantitativa, realizado entre 75 portadores de hipertensão arterial (HA) seguidos no ambulatório de um hospital-escola de nível terciário, no interior paulista, realizado no período de setembro de 2008 a abril de 2009, tendo por objetivo avaliar a adesão ao tratamento. Para a coleta de dados foram utilizados três instrumentos: um relativo a dados sociodemográficos, da doença e do tratamento; o Teste de Morisky e Green (TMG) para avaliar a adesão ao tratamento medicamentoso e o Instrumento de Avaliar Atitudes Frente à Tomada de Remédios (IAAFTR). Os testes estatísticos foram realizados por meio do software Statistica 8.0, e os resultados foram considerados significativos quando o nível de significância foi (p <0,05). Os sujeitos possuíam idade média de 61,5 ±10,36 anos, 52,0% eram do sexo feminino, 85,3% brancos, 70,7% casados, 48,0% aposentados e 24,0% do lar, 65,3% possuíam ensino fundamental incompleto, média de 3,08 ±1,99 filho, 94,7% residiam com outros membros da família, 81,3% informaram renda familiar entre um e três salários mínimos; 48,0% apresentaram valores de pressão arterial (PA) maiores que 140X90mmHg, 48,0% eram obesos, 80,6% dos homens e 94,9% das mulheres apresentaram circunferência da cintura com valores alterados. A média do tempo de diagnóstico da hipertensão arterial sistêmica (HAS) foi de 15,57 ±9,61 anos. As principais comorbidades identificadas foram: diabetes mellitus (54,3%) e dislipidemia (46,6%). A média dos medicamentos utilizados foi de 5,1 comprimidos/dia, sendo os mais comumente utilizados os hipoglicemiantes (58,7%) e os antiagregantes plaquetários (54,8%). A média de medicamentos usados para o tratamento da HA foi de 3 comprimidos/dia, sendo que os diuréticos foram os mais usados (84,0%). Quando avaliados pelo TMG, 21 (28,0%) apresentaram adesão ao tratamento; pela utilização do IAAFTR 37 (49,3%) mostraram atitudes positivas frente à tomada dos medicamentos. Entre aqueles que apresentaram adesão pelo TMG, 16 (76,2%) também apresentaram atitudes positivas quando avaliados pelo IAAFTR. A prevalência de controle da PA foi maior para os que tiveram adesão (66,7%) e para aqueles com atitudes positivas (64,9%). Houve significância estatística para o sexo e atitude frente à tomada dos medicamentos em relação ao controle da PA. Os valores de PA foram menores para os que tiveram adesão pelo TMG e que apresentaram atitudes positivas quanto à tomada dos medicamentos (p <0,05). Em relação aos fatores de risco para a HAS, 64,0% não praticavam exercício físico; 9,3% eram fumantes; 17,3% faziam uso de bebida alcoólica e 54,7% diziam ser estressados; 96,0% citaram antecedentes familiares para doenças cardiovasculares. Diante deste contexto permanece um desafio quanto à necessidade de revisão das medidas educativas instituídas no sentido de possibilitar alternativas que possam melhorar, na prática, a adesão dos portadores de HA ao tratamento medicamentoso, o controle da PA e a mudança nos fatores de risco para a HAS. / It is a cross-section descriptive study of quantitative approach, carried out with 75 hypertensive outpatients of tertiary level, in upstate São Paulo, carried out from September 2008 to April 2009, aiming to evaluate adherence to the treatment. Three questionnaires were used to collect the data: one about socio-demographic data regarding the disease and the treatment; the Morisky-Green Test, to assess the adherence to the drug-based treatment and the Questionnaire to Evaluate Attitudes Towards Taking Medicines. The statistical tests were applied by means of the software Statistica 8.0, and the results were considered significant whenever the significance level was (p<0.05). The subjects average age was 61.5 ±10.36 years, 52.0% were women, 85.3% Caucasians, 70.7% married, 48.0% retired and 24.0% housewives, 65.3% did not finish primary education, they had on average 3.08 ±1.99 children, 94.7% lived with other family members, 81.3% stated that their familly income was between one and three minimum wages; 48.0% had blood pressure readings above 140X90 mmHg, 48.0% were overweight, 80.6% of the men and 94.9% of the women had unhealthily large waist circumferences. Average hypertension diagnosis time (HT) was 15.57 ±9.61 years. The most important comorbities identifed were: diabetes mellitus (54.3%) e dyslipidemia (46.6%). The average of the medications used was 5.1 pills/day, and the most commonly used drugs were hypoglycemiants (58.7%) and platelet antiaggregant (54.8%). The average of the medications used for the treatment of HT was 3 pills/day, and the diuretics were the most used ones (84.0%). When evaluated with the Morisky-Green test, 21 (28.0%) showed adherence to the treatment, by means of the Questionnaire to Evaluate Attitudes Towards Taking Medicines, 37 (49.3%) showed positive attitudes towards the taking the medicines. Those that showed adherence through the Morisky-Green test also showed positive attitudes when evaluated by means of the Questionnaire to Evaluate Attitudes Towards Taking Medicines. The prevalence of control of the blood pressure was higher for those who had adherence (66.7%) and for those with positive attitudes (64.9%). Gender and attitude towards taking medicines had statistical significance to the control of blood pressure. Blood pressure readings were lower in hypertensives that had adherence according to the Morisky- Green test and that had positive attitudes toward taking the medicines (p<0.05). Regarding the risk factors for HT, 64.0% did not practice physical exercise; 9.3% were smokers; 17.3% drank alcoholic drinks and 54.7% reported being stressed; 96% cited family antecedents of cardiovascular disease. In face of this context, there remains the challenge of reviewing the current educative measures to enable alternatives that may improve, in practice, the adherence of hypertensives to the drug-based treatment, the control of blood pressure and the change in the risk factors for HT.

High blood pressure or hypertension is a major public health issue that affects more than 50% of adults in the United States. Hypertension is the leading risk factor for multiple cardiovascular events including stroke and myocardial infarction. In general, hypertension is considered a disease of the aged population as 2/3rds of adults over 65 are hypertensive. Critically, a sex dependent component exists as females under age 50 are less likely to develop hypertension than males. Dietary sodium intake significantly influences blood pressure regulation and its importance is underscored by the salt-sensitivity of blood pressure, which is characterized by acute increases in blood pressure in response to dietary salt intake. The salt-sensitivity of blood pressure is prevalent in 25% of normotensive individuals and 50% of hypertensive individuals. Coupled with statistics that show Americans on average consume 2 g of sodium in excess of the recommended daily allowance, the risk for developing salt-sensitive hypertension is drastically higher in salt-sensitive individuals. Moreover with age, there is an increase in the prevalence and severity of salt-sensitivity. Taken together, these findings underscore the need for novel therapeutics to combat hypertension. The pathophysiology of the salt-sensitivity of blood pressure and age dependent hypertension has been attributed in part to excessive sympathetic outflow that can drive increases in sodium reabsorption. Excessive sympathetic outflow via the release of norepinephrine has been linked to increased activity of a key renal sodium transporter, the sodium chloride cotransporter (NCC). This thesis investigates the adrenergic signaling pathway by which excessive sympathetic outflow drives NCC activity and sodium reabsorption as well investigates the mechanisms underlying sex differences in age dependent hypertension. Our findings demonstrate that 1) norepinephrine mediates its influence on NCC activity via an α1-adrenoceptor gated pathway involving WNK/SPAK/OxSR1 kinase signaling, 2) α1-adrenoceptor antagonism can prevent and attenuate the development and maintenance of salt-sensitive hypertension, 3) β-adrencoptor antagonism has no effect on NCC activity, 4) in male rats age dependent salt-sensitivity of blood pressure and hypertension is associated with age dependent- increases in NCC activity and impairments in renal sodium handling, and 5) female rats do not develop age dependent hypertension or salt-sensitivity of blood pressure. Collectively, these results support a sympathetic model of NCC regulation that plays a key role in salt-sensitive hypertension and age dependent hypertension. / 2021-05-26T00:00:00Z

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13370号 / 論医博第2207号 / 新制||医||1047(附属図書館) / (主査)教授 大鶴 繁, 教授 中山 健夫, 教授 髙橋 良輔 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18864号 / 医博第3975号 / 新制||医||1008(附属図書館) / 31815 / 京都大学大学院医学研究科医学専攻 / (主査)教授 木村 剛, 教授 坂田 隆造, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM