Class of 2005 Abstract / Objectives: To evaluate results of a hypertension (HTN) screening provided to patients by community pharmacists at various Bashas’ United Drug Stores. Information evaluated includes risk factors for HTN and blood pressure values. Methods: This is a retrospective study analyzing results documented during clinical services provided at community pharmacies in Tucson and Phoenix, Arizona between December 2002 and January 2004. Data from 535 patients was collected. Data included risk factors (e.g. age, tobacco use, cardiovascular exercise, family history of HTN) and a blood pressure measurement by a pharmacist. For analysis, patients were separated into two groups based on HTN diagnosis status. The two groups were compared across each risk factor variable and blood pressure measurements. Results: Seven patients were excluded because they did not specify previous HTN status, leaving a total of 528 patients. Significant differences were found between the two groups regarding the following characteristics: age (p < 0.001), HTN management with drugs (p < 0.001), cardiovascular exercise (p < 0.05), family history of HTN (p < 0.001), salt intake (p < 0.001), diabetes (p < 0.001), measured systolic blood pressure (p < 0.001) and diastolic blood pressure (p < 0.05). Implications: Patients with diagnosed HTN were determined to be older, more likely to receive HTN treatment, at a greater level of cardiovascular exercise, greater family history of HTN, more likely diagnosed with diabetes and had a higher systolic and diastolic measurement taken by the pharmacist when compared to the undiagnosed group.

Objective: I sought to determine the systolic intensification threshold, time-to-intensification and time-to-follow-up associated with the lowest risk of cardiovascular events or death in primary care patients with hypertension. Methods: A retrospective cohort study of 88,756 patients was performed. Systolic intensification threshold, time-to-intensification and time-to-follow-up were analyzed with respect to risk of acute cardiovascular event or death. The Cox model was adjusted for age, sex, smoking status, socioeconomic deprivation, history of diabetes, cardiovascular disease or CKD, Charlson Comorbidity Index, BMI, medication possession ratio, and baseline blood pressure. Results: During median follow-up of 37.4 months, 9,985 participants experienced acute cardiovascular event or death (11.3%). Systolic intensification thresholds of 130-150 mmHg were associated with no difference in risk, while higher thresholds were associated with progressively greater risk. Risk increased progressively from the lowest (0-1.4 months) to the highest quintile of time to medication intensification. The highest quintile of time to-follow-up (>2.7 months) was also associated with increased risk. Conclusions: Systolic intensification threshold higher than 150 mmHg, delays of greater than 1.4 months before medication intensification following systolic blood pressure elevation, and delays of greater than 2.7 months before blood pressure follow-up following medication intensification were associated with increased risk for acute cardiovascular events or death.

L’hypertension artérielle chronique représente le premier facteur de risque de l’AVC ischémique, mais elle en est aussi le principal facteur aggravant. Les mécanismes à l’origine du risque ischémique lié à l’hypertension ne sont pas encore entièrement compris. Plusieurs études ont montré l’existence d’une forte composante inflammatoire délétère impliquée dans la physiopathologie de l’hypertension. Au niveau cérébral, la présence d’une intense réactivité microgliale hypothalamique, participant à l’aggravation de la pathologie a été observé. Dans le travail présenté ici, nous nous sommes intéressés à l’impact de l’hypertension artérielle sur l’état inflammatoire du cortex cérébral, une région particulièrement touchée lors d’un AVC ischémique chez le patient. Nous avons tiré parti de la souche transgénique de souris CX3CR1GFP/+ pour l’imagerie de la dynamique microgliale, principal acteur de l’immunité cérébrale. Par une analyse in vivo réalisée en microscopie biphotonique, nous avons montré que l’hypertension induite par infusion chronique d’angiotensine-II altère la morphologie de la microglie, mais surtout sa capacité de surveillance du parenchyme cérébral et sa capacité cicatricielle. Nous avons aussi montré que ce type d’hypertension endommage la structure et la fonctionnalité des vaisseaux corticaux. L’ensemble de ces résultats pourrait expliquer, au moins en partie, la sensibilisation du cerveau aux lésions ischémiques par l’hypertension artérielle, avant même la survenue de l’AVC. / Chronic high blood pressure is ischemic stroke’s leading risk factor, but it is also its main aggravating factor. The mechanisms underlying hypertension-induced ischemic brain lesion exacerbation are not yet fully understood. Several studies highlighted the existence of a strong inflammatory component in the pathophysiology of hypertension. In the brain, the presence of intense hypothalamic microglial reactivity, contributing to the pathology worsening has been shown. In this work, we focused on the impact of high blood pressure on the inflammatory state of the cerebral cortex, a region particularly affected by ischemic stroke in the patient. We took advantage of the CX3CR1GFP/+ mice transgenic strain for imaging microglia dynamics. By using in vivo two-photon microscopy, we have shown that hypertension induced by chronic infusion of angiotensin-II alters the microglia morphology, especially its parenchymal surveilling activity and its cicatricial capacity. We have also shown that this type of hypertension disrupts the structure and the functioning of cortical vessels. All of these results can explain, at least in part, the brain sensitization to ischemic lesions under arterial hypertension, before the onset of stroke.

This study investigated the cellular basis for the enhanced ganglionic responsiveness to NK1 agonists in the spontaneously hypertensive rat (SHR) in comparison to their normotensive counterpart, the Wistar-Kyoto (WKY) rat. Rats for in vivo studies were anesthetized with pentobarbital and treated with chlorisondamine (10.5 μmol/kg). Extracellular recordings from the external carotid nerve showed a greater responsiveness of decentralized SHR superior cervical ganglia (SCG) to intravenous injection of SP (32 nmol/kg). Blood pressure and heart rate were increased in SHRs, whereas WKY rats responded with a decrease in blood pressure and only slight tachycardia. Membrane properties of SCG neurons, as shown by intracellular microelectrode recordings, were similar between strains. Picospritzer application of the NK1 agonist GR-73632 (100 μM, 1 s) evoked slow depolarization and increased neuron excitability. Spontaneous firing was evoked only in some neurons. Depolarization amplitudes were similar between strains; however, the NK1 agonist depolarized a greater number of neurons in hypertensive rats. In conclusion, SHRs are more responsive to ganglion stimulation by NK1 agonists due to a greater number of responsive cells within the SCG rather than an enhanced responsiveness of individual neurons.

The diagnosis of primary pulmonary hypertension (PPH) and prediction of its course, whether treated or untreated, presents several problems. These are of particular relevance when selection of patients for, and timing of heart-lung transplantation is being considered. I performed a retrospective study on patients with PPH and chronic large vessel thromboembolic pulmonary hypertension (TPH) seen at Groote Schuur Hospital between 1957 and 1985 in an attempt to: 1. Establish the diagnostic and prognostic value of clinical features, lung function tests, cardiac catheterisation, isotope lung scans and, in the PPH group, response to therapy; 2. Review our experience of the effects of treatment with vasodilators and oral anticoagulants, and the results of heart and lung transplantation in the PPH group; 3. Attempt to identify features which could be used to predict prognosis in PPH; and thereby 4. Define criteria for selecting PPH patients whose prognosis could be improved by heart-lung transplantation.

Includes bibliographical references / Pulmonary hypertension (PH) is defined as a rise in the pressure in the pulmonary arteries resulting from a variety of diseases including chronic infectious diseases, lung diseases and left heart diseases (LHD). It is a global health problem and accounts for a substantial portion of cardiovascular disease. PH due to LHD (PH-LHD) is credited to be the most common form of PH worldwide and is associated with adverse outcomes. Considering the suggestions of high prevalence and potential adverse outcomes of PH in sub-Saharan Africa (SSA), the investigation of the etiologies, clinical profile, correlates, and outcomes of PH-LHD in this region is a medical priority. Methods: Through a systematic review, we assessed existing evidence on the predictors of PH-LHD outcomes. Then, through two prospective multinational cohort registries, we investigated 1) the spectrum of PH in SSA; 2) the clinical profile and 6 months outcome of PH-LHD; 3) the role of electrocardiogram for diagnosing PH and 4) its prognostic role in heart failure (HF). PH was diagnosed by echocardiography in the context of clinical suspicion. Results: In high income countries, PH-LHD is almost invariably associated with increased mortality risk, but the effects on hospitalization are yet to be fully characterized. All groups of PH are found in SSA with LHD being the major cause. PH-LHD affects young people and is predominantly due to HF and rheumatic valvular heart disease. In these patients, left atrium size and tricuspid annular plan excursion are predictors of pulmonary pressures, and PH-LHD predicts short term hospitalization but not mortality. A normal electrocardiogram is very rare in patients with PH, but electrocardiogram criteria of right ventricular strain are rather rare and non-specific. Similarly, electrocardiogram abnormalities are frequent among Africans with HF, some have prognostic value for mortality risk. Conclusion: PH-LHD is the most common form of PH in SSA, with affected patients presenting with advanced disease, and it is associated with adverse outcomes. ECG abnormalities are prevalent in both PH and HF, but few of these abnormalities have prognostic value for mortality risk. Evaluating the efficacy and safety of low-cost and available drugs in reducing HF hospitalizations in PH-LHD is a key future priority. Improving early diagnosis of PH should also be encouraged.

Blood pressure is one of the most important indicators of human health. The symptoms of many cardiovascular diseases like stroke, atrial fibrillation, and acute myocardial infarction are usually indicated by the abnormal variation of blood pressure. Severe symptoms of diseases like coronary syndrome, rheumatic heart disease, arterial aneurysm, and endocarditis also usually appear along with the variation of blood pressure. Most of the current blood pressure measurements rely on the Korotkoff sounds method that focuses on one-time blood pressure measuring but cannot supervise blood pressure continuously, which cannot effectively detect diseases or alert patients. Previous researches indicating the relationship between photoplethysmogram (PPG) signal and blood pressure brought up the new research direction of blood pressure measurement method. Ideally, with the continuous supervision of the PPG signal, the blood pressure of the subject could be measured longitudinally, which matches the current requirements of blood pressure measurement better as an indicator of human health. However, the relationship between blood pressure and PPG signal is very comprehensive that is related to personal and environmental status, which leads to the research challenge for many previous works that tried to find the mapping from PPG signal to blood pressure without considering other factors. In this thesis, we propose two statistical methods modeling the comprehensive relationships among blood pressure, PPG signals, and other factors for blood pressure prediction. We also express the modeling and predicting process for the real data set and provide accurate prediction results that achieve the international blood pressure measurement standard. In the first part, we propose the Independent Variance Components Mixed- model (IVCM) that introduces the variance components to describe the relationship among observations. The relationship indicators are collected as information to divide observations into different groups. The latent impacts from the properties of groups are estimated and used for predicting the multiple responses. The Stochastic Approximation Minorization-maximization (SAM) algorithm is used for IVCM model parameter estimation. As the expansion of Minorization-maximization (MM) algorithm, the SAM algorithm could provide comparable-level estimations as MM algorithm but with faster computing speed and less computational cost. We also provide the subsampling prediction method for IVCM model prediction that could predict multiple responses variables with the conditional expectation of the model random effects. The prediction speed of the subsampling method is as fast as the SAM algorithm for parameter estimation with very small accuracy loss. Because the SAM algorithm and subsampling prediction method requires assigning tuning parameters, a great amount of simulation results are provided for the tuning parameter selection. In the second part, we propose the Groupwise Reweighted Mixed-model (GRM) to describe the variation of random effects as well as the potential components of mixture distributions. In the model, we combine the properties of mixed-model and mixture model for modeling the comprehensive relationship among observations as well as between the predictive variables and the response variables. We bring up the Groupwise Expectation Minorization-maximization (GEM) algorithm for the model parameter estimation. Developed from MM algorithm and Expectation Maximization (EM) algorithm, the algorithm estimates parameters fast and accurate with adopting the properties of the diagonal blocked matrix. The corresponding prediction method for GRM model is provided as well as the simulations for the number of components selection. In the third part, we apply the IVCM model and the GRM model in modeling real data and predicting blood pressure. We establish the database for modeling blood pressure with PPG signals and personal characteristics, extract PPG features from PPG signal waves, and analyze the comprehensive relationship between PPG signal and blood pressure with the IVCM model and the GRM model. The blood pressure prediction results from different models are provided and compared. The best prediction results not only achieve the international blood pressure measurement standard but also show great performance in high blood pressure prediction

Blood pressure is one of the most important indicators of human health. The symptoms of many cardiovascular diseases like stroke, atrial fibrillation, and acute myocardial infarction are usually indicated by the abnormal variation of blood pressure. Severe symptoms of diseases like coronary syndrome, rheumatic heart disease, arterial aneurysm, and endocarditis also usually appear along with the variation of blood pressure. Most of the current blood pressure measurements rely on the Korotkoff sounds method that focuses on one-time blood pressure measuring but cannot supervise blood pressure continuously, which cannot effectively detect diseases or alert patients. Previous researches indicating the relationship between photoplethysmogram (PPG) signal and blood pressure brought up the new research direction of blood pressure measurement method. Ideally, with the continuous supervision of the PPG signal, the blood pressure of the subject could be measured longitudinally, which matches the current requirements of blood pressure measurement better as an indicator of human health. However, the relationship between blood pressure and PPG signal is very comprehensive that is related to personal and environmental status, which leads to the research challenge for many previous works that tried to find the mapping from PPG signal to blood pressure without considering other factors. In this thesis, we propose two statistical methods modeling the comprehensive relationships among blood pressure, PPG signals, and other factors for blood pressure prediction. We also express the modeling and predicting process for the real data set and provide accurate prediction results that achieve the international blood pressure measurement standard. In the first part, we propose the Independent Variance Components Mixed- model (IVCM) that introduces the variance components to describe the relationship among observations. The relationship indicators are collected as information to divide observations into different groups. The latent impacts from the properties of groups are estimated and used for predicting the multiple responses. The Stochastic Approximation Minorization-maximization (SAM) algorithm is used for IVCM model parameter estimation. As the expansion of Minorization-maximization (MM) algorithm, the SAM algorithm could provide comparable-level estimations as MM algorithm but with faster computing speed and less computational cost. We also provide the subsampling prediction method for IVCM model prediction that could predict multiple responses variables with the conditional expectation of the model random effects. The prediction speed of the subsampling method is as fast as the SAM algorithm for parameter estimation with very small accuracy loss. Because the SAM algorithm and subsampling prediction method requires assigning tuning parameters, a great amount of simulation results are provided for the tuning parameter selection. In the second part, we propose the Groupwise Reweighted Mixed-model (GRM) to describe the variation of random effects as well as the potential components of mixture distributions. In the model, we combine the properties of mixed-model and mixture model for modeling the comprehensive relationship among observations as well as between the predictive variables and the response variables. We bring up the Groupwise Expectation Minorization-maximization (GEM) algorithm for the model parameter estimation. Developed from MM algorithm and Expectation Maximization (EM) algorithm, the algorithm estimates parameters fast and accurate with adopting the properties of the diagonal blocked matrix. The corresponding prediction method for GRM model is provided as well as the simulations for the number of components selection. In the third part, we apply the IVCM model and the GRM model in modeling real data and predicting blood pressure. We establish the database for modeling blood pressure with PPG signals and personal characteristics, extract PPG features from PPG signal waves, and analyze the comprehensive relationship between PPG signal and blood pressure with the IVCM model and the GRM model. The blood pressure prediction results from different models are provided and compared. The best prediction results not only achieve the international blood pressure measurement standard but also show great performance in high blood pressure prediction

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BACKGROUND Worldwide, hypertension is the third leading risk factor contributing to death, surpassed only by malnutrition and smoking. 1 Hypertension is common and treatable and because uncontrolled hypertension has serious consequences, preventive measures and control of blood pressure should be a high priority. A healthy lifestyle remains the cornerstone of the management of blood pressure (BP) for all severities of hypertension. It is possible to prevent the development of hypertension and to lower blood pressure levels by simply adopting a healthy lifestyle. 2 Health care workers can assess and contribute to the management of hypertension with exercise adequately if the patient is educated and convinced that lifestyle changes are essential and indeed the most cost effective method of obviating cardiovascular disease. METHODS Patients with hypertension (N=110) were identified from a cohort of patients attending the outpatients department of Carletonville Hospital, a district hospital situated in the mining town of Carletonville, South Africa, and were then invited to participate in the study. A crosssectional descriptive study design was used to determine the knowledge and attitudes of these patients with respect to the importance of lifestyle modification in the management of hypertension. This was achieved by administering a questionnaire. Descriptive and inferential statistical methods were employed to analyze the data. RESULTS The largest number of respondents fell in the 50-59 year old age groups (28%). Females (62%) made up a significant majority of the study population. The population breakdown included the following: Black respondents were 75%, while 24 % were white and 1% coloured. Body Mass Index was more than 25 in 81% of the respondents and 84% of the population had schooling levels below high school. Fifty seven percent (57%) of the respondents ate fried foods regularly, 70 % cooked with salt, 18% add salt to their food, while 14% ate red meat regularly and 26 % consumed alcohol, with 6 % having more than 3 beers/day. The majority of participants led sedentary lifestyles according to the physical activity score, with 74% having little or no activity. At the time of the study 69% had blood pressure (BP) levels above 140/90 mmHg with only 42% knowing what their normal BP should be. Seventy seven percent (77%) believed that exercise lowers BP, and only 30% reported having received such advice from a medical professional. Ninety five percent (95%) believed that a balanced diet is important in controlling hypertension and fifty one percent (51%) reported having being advised by a medical professional about a balanced diet. Ninety four percent (94%) knew that adding salt to food affects BP and sixty nine percent (69%) reported having being told by a medical professional about the effects of excessive salt intake in their diets. Eighty percent (80%) believed that alcohol affects blood pressure and forty four percent (44%) reported having received such information from a medical professional. Seventy five percent (75%) believed that smoking affects BP and thirty six percent (36%) got this information from a medical professional. DISCUSSION The results indicate that respondents reported having received advice about lifestyle modification from medical professionals. The advice varied between areas of lifestyle change, which included education on diet, alcohol, smoking and exercise. The most frequently given advice was on diet and salt intake, with exercise being the least often information provided to the patients by medical professionals. Reduced salt intake advice was the most frequently reported (69%), followed by a balanced diet (51%), reduced alcohol intake (44%), not smoking (35%) and benefits of exercise (30%).Despite this most of the respondents were leading sedentary lifestyles, were overweight (BMI>25) and had BP`s greater than 140/90 mmHg . The reasons provided for not exercising varied from “not being used to it”, “no- time” to “body pain”. Twenty one percent (21%) were not on a proper diet due to financial reasons, 16% stated lack of information as the reason and 9% just found unhealthy food to be very tempting. CONCLUSION The results of this study suggest that although patients do receive advice on lifestyle modification, it is not effective in changing patient behavior, and may therefore be inadequate and not emphasized enough and also not all patients are advised by medical professionals about lifestyle change. The reason for this is not known. Greeff (2006) in his study emphasized that building a trusting relationship between the healthcare worker and the patient is one of the most important aspects when motivating patients. 2