Thesis (M.S.)--The University of North Carolina at Greensboro, 2009. / Directed by Margaret Savoca; submitted to the Dept. of Nutrition. Title from PDF t.p. (viewed Jun. 7, 2010). Includes bibliographical references (p. 71-79).

Management of hypertension and its complications requires health care providers to understand the reason for developing the disease. Complications of hypertension (HTN) are more prevalent when patient interventions are not consistently performed by staff. A gap in staff knowledge regarding the management of patients with HTN was noted at an outpatient clinic in the southwestern United States. A staff education project based on the Eighth Joint National Committee (JNC-8) guidelines for HTN management was developed to address the gap in knowledge. This DNP project sought to understand the impact of an evidence-based staff education program in improving the knowledge of nursing staff on HTN management. The health belief model and social cognitive theory guided the project. Three expert panelists evaluated the education program content and agreed that the content was relevant to clinical practice and would improve staff knowledge regarding management of HTN. Eight nurses participated in the education program, first completing a pretest questionnaire followed by educational program content in digital format. Participants reviewed the program for 1 week followed by a PowerPoint presentation at a staff meeting. Posttest questionnaires were completed by 7 participants using a 5-point Likert scale ranging from completely unaware to completely aware. Posttest results indicated that nursing staff knowledge increased to completely aware (100%) of the JNC-8 guidelines for HTN management compared with completely unaware before the program. The project emphasizes the potential for positive social change when translating evidence to practice through staff education to improve patient management and outcomes for the treatment of HTN.

L'hypertension artérielle constitue un facteur de risque majeur et modifiable des événements cardiovasculaires. La haute variabilité de la pression artérielle rend son évaluation par la méthode classique auscultatoire au sphygmomanomètre inexacte, particulièrement chez les personnes âgées. Ainsi, des méthodes de mesure complémentaires se sont développées, comme l'automesure de la pression artérielle à domicile. Nous nous sommes intéressés à l'apport de cette méthode, spécialement chez les personnes âgées, à partir des données transversales et longitudinales de l'étude 3C-HBPM portant sur un échantillon de 1814 sujets âgés de 73 à 97 ans. Nous avons tout d'abord montré que la faisabilité de l'automesure tensionnelle à domicile était excellente chez les personnes âgées en population générale. Nous avons également montré que le diagnostic tensionnel basé sur les valeurs mesurées au centre était erroné dans presque 30% des cas, et que l'hypertension artérielle était sous-diagnostiquée chez les personnes âgées. En outre, l'hypertension blouse blanche et masquée étaient associées à un risque accru de développer une hypertension soutenue un an plus tard. Enfin, nos résultats suggèrent que la variabilité tensionnelle pourrait être impliquée dans le sur-risque vasculaire des hypertendus masqués. Ces résultats sont en faveur de l'utilisation de l'automesure à domicile dans le cadre du suivi tensionnel des personnes âgées, et offrent de nouvelles perspectives de prévention vasculaire

Cirrhosis is characterized by the progressive development of portal hypertension. Portal hypertension, associated with sodium retention, leads to the formation of ascites. Ascites may be difficult to treat and, thereby, become "refractory". To date, the mortality of patients with refractory ascites remains high. In order to offer patients adequate treatment, it is important to identify complications that may develop and the factors of good and poor prognosis affecting their survival. One can retain five specific complications of cirrhosis with ascites: hepatorenal syndrome, spontaneous bacterial peritonitis, paracentesis induced circulatory dysfunction, hepatic hydrothorax and dilutional hyponatremia. This thesis reported an update of pathogenesis, complications and treatment of refractory ascites. Our original clinical research has, meanwhile, focused on the identification of different prognostic factors in refractory ascites in direct relation to these five complications. We have focused on the effect of the administration of beta blockers in patients with refractory ascites: this treatment is widely prescribed for prevention of gastrointestinal bleeding. It is associated in these patients with higher mortality and a high incidence of paracentesis induced circulatory dysfunction. We specified that the severe hyponatremia, leading to withhold diuretic therapy, is a more accurate prognostic factor than the MELDNa score in refractory ascites. With regard to the hepatorenal syndrome of slow onset (type 2), we emphasized the high frequency of this syndrome in refractory ascites. We showed that there was an association between the level of portal hypertension and the incidence of spontaneous bacterial peritonitis. Furthermore, we demonstrated that the presence of bacterial DNA in ascites of outpatients suffering from refractory ascites was particularly low. The detection of this DNA is not a precursor to infection of ascites. In conclusion, with a systematic analysis of various prognostic factors related to complications of ascites in cirrhotic patients, this work gives a better understanding of their chances of survival. This will allow a more adequate stratification in the decision trees for a cure of the disease such as liver transplantation. / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

An educational module, based on evidence-based practice (EBP) guidelines by the 8th Joint National Committee (JNC 8) and the American College of Cardiology (ACC), was created and implemented to determine if its implementation would impact the knowledge of clinic staff regarding current EBP guidelines about self-management of hypertension (HTN). The module has the potential to contribute to the resolution of patient noncompliance on HTN treatment and management by increasing nursing staff proficiency in knowledge transfer to patients on effective self-management of their health condition. The creation of the module was guided by the concept of need or asset assessment and the theory of planned behavior. The module was composed of 2 short lecture presentations on HTN, current EBP guidelines on lifestyle modifications, and proper blood pressure measurement. The module also included pre- and postlecture surveys to evaluate knowledge and practices of staff, and reiterated the current guidelines and approaches presented in the lectures. Survey data were analyzed using McNemar’s test for paired and binary data. Results showed the agreement of all the staff in recognizing the utility of the module in standardizing their knowledge of current EBP guidelines on lifestyle modifications and blood pressure measurement procedures. The results also showed the enhancement of staff proficiency which might lead to efficient education of patients on effective HTN treatment and management protocol. This pathway has the potential to bring about social change by decreasing the incidence of patient noncompliance and improving patient health.

MCur / Department of Advanced Nursing Science / Noncompliance with antihypertensive treatment is a challenge for uncontrolled hypertension in both high income and middle income countries. Compliance to antihypertensive treatment and lifestyle modification plays a significant role in the control of hypertension and reduces the cardiovascular morbidity and mortality rate. The purpose of this study was to explore and describe contributory factors of noncompliance to treatment among patients diagnosed with hypertension in the Vhembe District of the Limpopo Province The study was conducted at the regional Hospital and nine Primary Health Care facilities in the rural community in the Vhembe District of the Limpopo Province. The study population consisted of those patients diagnosed with hypertension receiving treatment from the ten sampled health facilities. In this study, the target population included 134 noncompliant patients diagnosed with hypertension taking treatment at the sampled health facilities. This study used simple random sampling. The instrument used for data collection was self-administered questionnaire. Data was analysed using the Statistical Package for Social Sciences. The results of this current study reveal that participants aged 40 years and above (85.1%) were noncompliant to treatment compared to those of the same or less than 40 years old (14.9%). Also, it indicated that females were more frequently noncompliant to treatment (73.1%) compared to males (26.9%), which was statistically significant. The study revealed that the unmarried participants (64.9%) were more non-compliant with treatment when compared to the married participants (35.1%). The current findings demonstrate that 40.3% of noncompliant participants mentioned the reason being that they were feeling well. Various factors related to participants’ noncompliance with their antihypertensive treatment and lifestyle modification regimen were described. Health education should cover the nature of hypertension specifically emphasising causes, severity and potential complications. / NRF

Motivation In South Africa, various transitional changes parallel detrimental modifications in lifestyle behaviour of especially the lower socio-economic communities. We are currently double-burdened by a high prevalence of communicable and noncommunicable diseases such as diabetes, chronic respiratory and cardiovascular diseases, which is accompanied by a high cardiovascular mortality rate. Healthcare and treatment resources are limited and low-cost intervention strategies to lower this burden are urgently needed. Unhealthy lifestyle behaviours, such as excessive alcohol consumption and tobacco use, are known to augment inflammation as reflected by inflammatory markers such as C-reactive protein and interleukin-6, which are well-known risk factors for cardiovascular disease and mortality. Several studies showed the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in advanced disease states and that suPAR associates with different types of cancers, infectious diseases, diabetes, coronary artery disease and all-cause mortality. Since the discovery of suPAR in 1991, the role of this less known inflammatory marker in various diseases has been under debate. It was further reported that black individuals have higher suPAR levels than whites. However, whether an unhealthy lifestyle and cardiometabolic risk factors are related to suPAR, whether suPAR plays a role in the development of cardiovascular disease such as hypertension, and whether suPAR could predict all-cause and cardiovascular mortality, especially among the understudied black South African population, remain to be established. Aim The central aim of this thesis was to determine if suPAR associates with cardiovascular disease development in a black South African population. We therefore explored whether suPAR relates to lifestyle and cardiometabolic risk factors, associates with the development of hypertension and has prognostic value for cardiovascular and all-cause mortality over five years. Methodology This five-year prospective sub-study, which is embedded in the international Prospective Urban and Rural Epidemiology study, included black South African volunteers of ages older than 35 years from the North West province, South Africa. Baseline data collection took place in 2005 during which 2 010 men and women from urban and rural areas were examined. A total of 1 292 participants returned for examination and were followed-up for the first time in 2010. Of these participants, 214 were newly identified as being infected with the human immunodeficiency virus (HIV), while 233 died during the five year period. Standardised methods were used to capture all data and included health questionnaires (lifestyle factors, medication use, disease status and history, mortality outcome), cardiovascular and anthropometric measurements, as well as biochemical analyses of inflammatory markers (suPAR, C-reactive protein, interleukin-6), HIV status and relevant metabolic markers. In preparation for statistical analyses, non-Gaussian variables were logarithmically transformed. We compared means and proportions with independent t-tests, analysis of variance, analysis of covariance (for adjustments) and Chi-square tests, while dependent t-tests and McNemar tests were used for analysis of longitudinal data within individual groups. We determined relationships between variables with Pearson’s correlation coefficients. Independent relationships were determined with logistic regression, forward stepwise multiple regression and proportional Cox-regression analyses. Mortality rates were calculated using Kaplan-Meier survival function estimates and log-rank tests. In all cases, p≤0.05 were used to indicate statistical significance. Results and conclusions of each manuscript Three manuscripts were written in order to achieve the aim of this thesis. In the first manuscript we explored the cross-sectional relationships of suPAR with lifestyle and cardiometabolic risk factors in a black South African population. We showed that suPAR was independently associated with lifestyle behaviours, including alcohol consumption, as indicated by gamma-glutamyltransferase levels (β=0.24; p<0.001), tobacco use (β=0.13; p<0.001) and unemployment (β=0.07; p=0.039), despite no direct links with cardiometabolic factors such as blood pressure, dyslipidaemia, glycaemia or adiposity. These findings emphasise the important need to address lifestyle behaviours in order to limit the detrimental effect of modifiable risk factors on the health and mortality rate of this population. Secondly, we determined whether suPAR was associated with the development of hypertension over five years. We found that suPAR was higher and increased more prominently (14.2% vs. 6.94%; p=0.007) in participants that developed hypertensio than in those that remained normotensive. Change in systolic blood pressure was independently associated with baseline suPAR (β=0.14; p=0.043), while becoming hypertensive was associated with an increase in suPAR (odds ratio=1.41; p=0.015). Whether inflammation leads to the development of hypertension or vice versa, remains unclear. Our findings emphasise the need to acknowledge the role of inflammation in hypertension and may permit further investigation of the use of suPAR as a potential marker for early risk identification and intervention. The third manuscript investigated the prognostic value of suPAR, compared to other inflammatory markers C-reactive protein and interleukin-6, in all-cause and cardiovascular mortality. We showed for the first time in a black population that suPAR predicted both all-cause (hazard ratio=1.27; p=0.003) and cardiovascular mortality (hazard ratio=1.40; p=0.026), independent of interleukin-6. Future research is needed to clarify the mechanisms behind the association of suPAR with cardiovascular mortality and to explore the possibility of a suPAR cut-off value for early identification of those with increased risk for cardiovascular morbidity and mortality in this population. General conclusion In this thesis we showed for the first time that suPAR has potential as a marker of cardiovascular disease development in black South Africans. SuPAR associated with hypertension and independently predicted all-cause and cardiovascular mortality over five years. Our findings, that suPAR is independently associated with adverse health behaviours such as alcohol and tobacco use, lend support for the use of suPAR as a novel approach for early risk identification and intervention strategies, which may be effective in combatting the high cardiovascular disease burden among the black South African community. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Motivation In South Africa, various transitional changes parallel detrimental modifications in lifestyle behaviour of especially the lower socio-economic communities. We are currently double-burdened by a high prevalence of communicable and noncommunicable diseases such as diabetes, chronic respiratory and cardiovascular diseases, which is accompanied by a high cardiovascular mortality rate. Healthcare and treatment resources are limited and low-cost intervention strategies to lower this burden are urgently needed. Unhealthy lifestyle behaviours, such as excessive alcohol consumption and tobacco use, are known to augment inflammation as reflected by inflammatory markers such as C-reactive protein and interleukin-6, which are well-known risk factors for cardiovascular disease and mortality. Several studies showed the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in advanced disease states and that suPAR associates with different types of cancers, infectious diseases, diabetes, coronary artery disease and all-cause mortality. Since the discovery of suPAR in 1991, the role of this less known inflammatory marker in various diseases has been under debate. It was further reported that black individuals have higher suPAR levels than whites. However, whether an unhealthy lifestyle and cardiometabolic risk factors are related to suPAR, whether suPAR plays a role in the development of cardiovascular disease such as hypertension, and whether suPAR could predict all-cause and cardiovascular mortality, especially among the understudied black South African population, remain to be established. Aim The central aim of this thesis was to determine if suPAR associates with cardiovascular disease development in a black South African population. We therefore explored whether suPAR relates to lifestyle and cardiometabolic risk factors, associates with the development of hypertension and has prognostic value for cardiovascular and all-cause mortality over five years. Methodology This five-year prospective sub-study, which is embedded in the international Prospective Urban and Rural Epidemiology study, included black South African volunteers of ages older than 35 years from the North West province, South Africa. Baseline data collection took place in 2005 during which 2 010 men and women from urban and rural areas were examined. A total of 1 292 participants returned for examination and were followed-up for the first time in 2010. Of these participants, 214 were newly identified as being infected with the human immunodeficiency virus (HIV), while 233 died during the five year period. Standardised methods were used to capture all data and included health questionnaires (lifestyle factors, medication use, disease status and history, mortality outcome), cardiovascular and anthropometric measurements, as well as biochemical analyses of inflammatory markers (suPAR, C-reactive protein, interleukin-6), HIV status and relevant metabolic markers. In preparation for statistical analyses, non-Gaussian variables were logarithmically transformed. We compared means and proportions with independent t-tests, analysis of variance, analysis of covariance (for adjustments) and Chi-square tests, while dependent t-tests and McNemar tests were used for analysis of longitudinal data within individual groups. We determined relationships between variables with Pearson’s correlation coefficients. Independent relationships were determined with logistic regression, forward stepwise multiple regression and proportional Cox-regression analyses. Mortality rates were calculated using Kaplan-Meier survival function estimates and log-rank tests. In all cases, p≤0.05 were used to indicate statistical significance. Results and conclusions of each manuscript Three manuscripts were written in order to achieve the aim of this thesis. In the first manuscript we explored the cross-sectional relationships of suPAR with lifestyle and cardiometabolic risk factors in a black South African population. We showed that suPAR was independently associated with lifestyle behaviours, including alcohol consumption, as indicated by gamma-glutamyltransferase levels (β=0.24; p<0.001), tobacco use (β=0.13; p<0.001) and unemployment (β=0.07; p=0.039), despite no direct links with cardiometabolic factors such as blood pressure, dyslipidaemia, glycaemia or adiposity. These findings emphasise the important need to address lifestyle behaviours in order to limit the detrimental effect of modifiable risk factors on the health and mortality rate of this population. Secondly, we determined whether suPAR was associated with the development of hypertension over five years. We found that suPAR was higher and increased more prominently (14.2% vs. 6.94%; p=0.007) in participants that developed hypertensio than in those that remained normotensive. Change in systolic blood pressure was independently associated with baseline suPAR (β=0.14; p=0.043), while becoming hypertensive was associated with an increase in suPAR (odds ratio=1.41; p=0.015). Whether inflammation leads to the development of hypertension or vice versa, remains unclear. Our findings emphasise the need to acknowledge the role of inflammation in hypertension and may permit further investigation of the use of suPAR as a potential marker for early risk identification and intervention. The third manuscript investigated the prognostic value of suPAR, compared to other inflammatory markers C-reactive protein and interleukin-6, in all-cause and cardiovascular mortality. We showed for the first time in a black population that suPAR predicted both all-cause (hazard ratio=1.27; p=0.003) and cardiovascular mortality (hazard ratio=1.40; p=0.026), independent of interleukin-6. Future research is needed to clarify the mechanisms behind the association of suPAR with cardiovascular mortality and to explore the possibility of a suPAR cut-off value for early identification of those with increased risk for cardiovascular morbidity and mortality in this population. General conclusion In this thesis we showed for the first time that suPAR has potential as a marker of cardiovascular disease development in black South Africans. SuPAR associated with hypertension and independently predicted all-cause and cardiovascular mortality over five years. Our findings, that suPAR is independently associated with adverse health behaviours such as alcohol and tobacco use, lend support for the use of suPAR as a novel approach for early risk identification and intervention strategies, which may be effective in combatting the high cardiovascular disease burden among the black South African community. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Inappropriate modulation of the renin angiotensin system (RAS) can lead to derangements of blood pressure homeostasis in humans. Cyp1a1-mRen2.F transgenic rats were used to define the renal mechanisms underlying the development of angiotensin II-dependent hypertension. These transgenic rats were previously generated by introducing the mouse Ren2 gene into the rat genome under the control of a Cyp1a1 inducible promoter. The aim of the current investigation was to establish the contribution of renal function to the development of hypertension in the Cyp1a1- mRen2.F transgenic rat. Expression of the mRen2 transgene was induced by daily gavage of indole 3 carbinol (I3C) at the dose of 100mg/kg. Blood pressure was measured in conscious rats after 1, 3 or 7 days of treatment. The control group received the vegetable oil carrier for 7 days. In addition blood pressure, renal haemodynamics and excretory function were measured under thiobutabarbital anaesthesia. Transgene induction caused a progressive increase in blood pressure in a time dependent manner. Neither glomerular filtration rate nor renal blood flow was affected. This indicates proper function of renal autoregulation during the experimental time course. Tubular sodium reabsorption was significantly increased after the first day of transgene induction and this effect was sustained for the duration of treatment. A pharmacological approach was used to localize the increased reabsorption to a specific region of the nephron and was found to reflect increased activity of the thiazide-sensitive cotransporter (NCC). Chronic administration of thiazide significantly blunted the hypertensive response to transgene induction. Similarly AT1 receptor blockade attenuated the hypertensive phenotype and prevented the transgene-induced stimulation of NCC activity. In contrast, mineralocorticoid receptor blockade did not prevent the development of either hypertension or increased NCC activity. The current study suggests that the development of angiotensin II-dependent hypertension is mediated by increased tubular sodium reabsorption. Increased activity of NCC is a key hypertensive mechanism in this model and results directly from the actions of angiotensin II at the AT1 receptor; indirect aldosterone pathways do not play a major role.

Hypertension has been associated with causing deleterious effects to the cerebrovasculature, which are thought to underlie the formation of white matter lesions (WML) and predispose individuals to age related cognitive decline. In humans hypertension frequently occurs concomitantly with other vascular risk factors making it difficult to ascertain the primary mechanisms of hypertension in isolation. Animal models of hypertension have been used in an aid to establish the mechanisms of hypertension in isolation. To date the knowledge gleaned from animal models has undoubtedly provided an insight as to the role of hypertension and cerebrovasculature remodelling but, these models have limitations such as lack of genetically matched controls and the inability to control the severity of hypertension, restricting the understanding of the underlying mechanisms. All studies within this thesis used the Cyp1a1 Ren2 inducible hypertensive rat model, induced by dietary addition of Indole-3-carbinol (I3C), allowing the severity and duration of hypertension to be tightly controlled and compared to genetically matched controls. This thesis set out to address the hypothesis that sustained hypertension will lead to alterations to the structural integrity of the cerebrovasculature and white matter, which will be exacerbated with age and that hypertension will be associated with alterations to gene expression and cognitive function. Initially this thesis sought to investigate the effect of hypertension on the structural integrity of the vasculature in the Cyp1a1 Ren2 rat model. Firstly, blood pressure in the Cyp1a1 Ren2 rat model was characterised and it was found that the dietary addition of I3C, caused a sustained level of increased blood pressure in all three cohorts. Cerebrovascular alterations were found to consist of increased eNOS expression in the young brain, which progressed with increased duration of hypertension to vascular morphological alterations of decreased vessel width and a redistribution of tight junction protein claudin-5. With age, hypertensive vascular alterations consisted of increased eNOS expression and vascular density. Additionally, there was evidence that hypertension caused a vascular inflammatory response in the young and aged brain. Secondly, this thesis investigated the effect of hypertension on gene expression. Overall it was found that hypertension altered genes related to collagen growth factors, ion channels, eNOS related Map-Kinase pathway and inflammatory genes. Thirdly, this thesis sought to investigate the impact of hypertension on the overall structural integrity of the brain and white matter examining neurons, myelin, oligodendrocytes, axons and microglia, in several regions of the young and aged brain. In general, this study found that hypertension did not cause overt structural or myelin alterations in the majority of regions analysed, with only evidence of myelin alterations occurring within the subcortex of hypertensive animals from each of the young cohorts analysed. However, an adverse subcortical inflammatory response was found in hypertensive animals of the young 6-month cohort and also in hypertensive animals from the aged 4-month cohort, where the inflammatory response was not exclusive to the subcortex of hypertensive animals but also occurred in multiple white matter tracts. Lastly this thesis chose to examine the effect of hypertension on cognitive function, specifically spatial reference and working memory using the Morris water maze and found no evidence of alterations in the cognitive functions examined. Conclusions The results presented within this thesis demonstrated that hypertension in isolation leads to modest alterations to the integrity of the cerebrovasculature and white matter, with no evidence of alterations to specific cognitive functions examined, demonstrating the importance of studying hypertension in isolation. Additionally, this study highlights the initial hypertensive induced alterations to the cerebrovasculature, such as endothelial signalling, vascular structure and inflammation, providing a window for therapeutic intervention at a time point when there are minimal alterations to the overall structural integrity of the brain. Future studies in this model should concentrate on examining different severities of hypertension and also hypertension concomitantly with other vascular risk factors to try and recapitulate pathological alterations found in humans.