Motivation A close association exists between hypertension and arterial stiffness. Whether the increased arterial stiffness seen in hypertensives are due to structural or functional adaptations in the vasculature is uncertain. Hypertension is more common in blacks and they have an increased arterial stiffness and higer stroke prevalence than white populations. Arterial stiffening, or a loss of arterial distensibility, increases the risk for cardiovascular events, including stroke and heart failure, as it increases the afterload on the heart, as well as creating a higher pulsatile load on the microcirculation. The stiffness of the carotid artery is associated with cardiovascular events, like stroke, and all-cause mortality. Furthermore, carotid stiffness is independently associated with stroke, probably because stiffening of the carotid artery may lead to a higher pressure load on the brain. Inflammation, endothelial activation, dyslipidemia, hyperglycemia and health behaviours may also influence hypertension and arterial stiffness. Limited information is availiable on these associations in black South Africans. The high prevalence of hypertension and cardiovascular disease in blacks creates the need for effective prevention and intervention programs in South Africa. Aim We aimed to compare the characteristics of the carotid artery between 5-year sustained hypertensive and normotensive black participants. Furthermore, we aimed to determine whether blood pressure, conventional cardio-metabolic risk factors, markers of inflammation, endothelial activation and measures of health behaviours are related to these carotid characteristics. Methodology This sub-study forms part of the South African leg of the multi-national Prospective Urban and Rural Epidemiology (PURE) study. The participants of the PURE-SA study were from the North West Province of South Africa, and baseline data collection took place in 2005 (N=2010), while follow-up data was collected five years later, in 2010 (N=1288). HIV-free participants who were either hypertensive or normotensive (N=592) for the 5-year period, and who had complete datasets, were included in this sub-study. The study population thus consists of a group of 5-year sustained normotensive (n=241) and hypertensive (n=351) black participants. Anthropometric measurements included height, weight, waist circumference and the calculation of body mass index (BMI). We included several cardiovascular measurements, namely brachial systolic- and diastolic blood pressure, heart rate, central systolic blood pressure, central pulse pressure and the carotid dorsalis-pedis pulse wave velocity. Carotid characteristics included distensibility, intima media thickness, cross sectional wall area, maximum and minimum lumen diameter. Biochemical variables that were determined included HIV status, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, fasting glucose, glycated haemoglobin (HbA1c), creatinine clearance, interleukin-6, C-reactive protein, intracellular adhesion-molecule-1 and vascular adhesion molecule-1. Health behaviours were quantified by measuring γ-glutamyltransferase and by self-reported alcohol, tobacco and anti-hypertensive, anti-inflammatory and lipid-lowering medication use. We compared the normotensive and hypertensive groups by using independent t-tests and chi-square tests. The carotid characteristics were plotted according to quartiles of central systolic blood pressure by making use of standard analyses of variance (ANOVA) and the analyses of co-variance (ANCOVA). Pearson correlations done in the normotensive and hypertensive Africans helped to determine covariates for the multiple regression models. We used forward stepwise multiple regression analyses with the carotid characteristics as dependent variables to determine independent associations between variables. Results and Conclusion The cardiovascular measures, including pulse wave velocity, were significantly higher in the hypertensive group (all p≤0.024). The lipid profile, markers of inflammation, endothelial activation and glycaemia, as well as health behaviours, did not differ between the hypertensives and normotensives after adjustments for age, sex, waist circumference, γ-glutamyltransferase, tobacco use and anti-hypertensive medication use. After similar adjustments, all carotid characteristics, except IMT, were significantly different between the groups (all p≤0.008). However, upon additional adjustment for cSBP, significance was lost. The stiffness and functional adaptation seen in this study are not explained by the classic cardio-metabolic risk factors, markers of endothelial activation or health behaviours of the participants. The differences that exist in terms of arterial stiffness between the normotensive and hypertensive groups may be explained by the increased distending pressure in the hypertensive group. Despite their hypertensive status, it seems that there are no structural adaptations in these hypertensive Africans. / MSc (Physiology), North-West University, Potchefstroom Campus, 2015

Motivation A close association exists between hypertension and arterial stiffness. Whether the increased arterial stiffness seen in hypertensives are due to structural or functional adaptations in the vasculature is uncertain. Hypertension is more common in blacks and they have an increased arterial stiffness and higer stroke prevalence than white populations. Arterial stiffening, or a loss of arterial distensibility, increases the risk for cardiovascular events, including stroke and heart failure, as it increases the afterload on the heart, as well as creating a higher pulsatile load on the microcirculation. The stiffness of the carotid artery is associated with cardiovascular events, like stroke, and all-cause mortality. Furthermore, carotid stiffness is independently associated with stroke, probably because stiffening of the carotid artery may lead to a higher pressure load on the brain. Inflammation, endothelial activation, dyslipidemia, hyperglycemia and health behaviours may also influence hypertension and arterial stiffness. Limited information is availiable on these associations in black South Africans. The high prevalence of hypertension and cardiovascular disease in blacks creates the need for effective prevention and intervention programs in South Africa. Aim We aimed to compare the characteristics of the carotid artery between 5-year sustained hypertensive and normotensive black participants. Furthermore, we aimed to determine whether blood pressure, conventional cardio-metabolic risk factors, markers of inflammation, endothelial activation and measures of health behaviours are related to these carotid characteristics. Methodology This sub-study forms part of the South African leg of the multi-national Prospective Urban and Rural Epidemiology (PURE) study. The participants of the PURE-SA study were from the North West Province of South Africa, and baseline data collection took place in 2005 (N=2010), while follow-up data was collected five years later, in 2010 (N=1288). HIV-free participants who were either hypertensive or normotensive (N=592) for the 5-year period, and who had complete datasets, were included in this sub-study. The study population thus consists of a group of 5-year sustained normotensive (n=241) and hypertensive (n=351) black participants. Anthropometric measurements included height, weight, waist circumference and the calculation of body mass index (BMI). We included several cardiovascular measurements, namely brachial systolic- and diastolic blood pressure, heart rate, central systolic blood pressure, central pulse pressure and the carotid dorsalis-pedis pulse wave velocity. Carotid characteristics included distensibility, intima media thickness, cross sectional wall area, maximum and minimum lumen diameter. Biochemical variables that were determined included HIV status, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, fasting glucose, glycated haemoglobin (HbA1c), creatinine clearance, interleukin-6, C-reactive protein, intracellular adhesion-molecule-1 and vascular adhesion molecule-1. Health behaviours were quantified by measuring γ-glutamyltransferase and by self-reported alcohol, tobacco and anti-hypertensive, anti-inflammatory and lipid-lowering medication use. We compared the normotensive and hypertensive groups by using independent t-tests and chi-square tests. The carotid characteristics were plotted according to quartiles of central systolic blood pressure by making use of standard analyses of variance (ANOVA) and the analyses of co-variance (ANCOVA). Pearson correlations done in the normotensive and hypertensive Africans helped to determine covariates for the multiple regression models. We used forward stepwise multiple regression analyses with the carotid characteristics as dependent variables to determine independent associations between variables. Results and Conclusion The cardiovascular measures, including pulse wave velocity, were significantly higher in the hypertensive group (all p≤0.024). The lipid profile, markers of inflammation, endothelial activation and glycaemia, as well as health behaviours, did not differ between the hypertensives and normotensives after adjustments for age, sex, waist circumference, γ-glutamyltransferase, tobacco use and anti-hypertensive medication use. After similar adjustments, all carotid characteristics, except IMT, were significantly different between the groups (all p≤0.008). However, upon additional adjustment for cSBP, significance was lost. The stiffness and functional adaptation seen in this study are not explained by the classic cardio-metabolic risk factors, markers of endothelial activation or health behaviours of the participants. The differences that exist in terms of arterial stiffness between the normotensive and hypertensive groups may be explained by the increased distending pressure in the hypertensive group. Despite their hypertensive status, it seems that there are no structural adaptations in these hypertensive Africans. / MSc (Physiology), North-West University, Potchefstroom Campus, 2015

The resistant hypertension is a disease difficult to diagnose and is associated with higher risk of cardiovascular events such as heart attack, stroke and sudden death. A considerable number of patients do not get effective control of the disease, despite the use of multiple drugs and high doses. Hyperactivation of the sympathetic nervous system is the pathophysiological basis for the ablation of afferent fibers, by applying radiofrequency energy in the renal arteries. This procedure, known as percutaneous sympathetic denervation has been shown to be a promising therapy and in recent years the results, with limited number of patients showed significant drop in blood pressure levels and cardiovascular risk. However, much of the reduction in risk can not be explained only by lowering blood pressure, emerging questions about treatment outcomes (use of multiple drugs / high doses) and assigning any failure of medication on independent effect vascular properties pressure. Vascular changes in micro and macrocirculation can not be fully observed by the peripheral measures, which required the understanding of endothelial dysfunction. The vascular endothelium is considered an active, dynamic tissue, so this dysfunction, in cases of high blood pressure, contributes to the development of atherosclerosis by promoting thrombosis, arterial stiffness and reduce tone and in the regulation of arterial flow. The identification of endothelin as a vasoconstrictor and the discovery of his release from the vascular endothelium suggested their involvement in the pathogenesis of hypertension and vascular disease, currently the most potent vasoconstrictor agent ever identified. We evaluated the reduction of blood pressure by sympathetic denervation in resistant hypertensive and one correlated their levels of endothelin of patients with cardiovascular disease. There were no complications, and at 18 months the average drop was 18 mmHg in systolic 24-ABPM and 19mmHg in central pressure. These two methods were shown to be equal in the assessment of therapeutic success. Higher levels of endothelin were present in cardiovascular disease may be a new marker of endothelial damage in heart disease. / A hipertensão arterial resistente é uma doença de difícil diagnóstico e está relacionada ao maior risco de eventos cardiovasculares, como infarto, acidente vascular cerebral e morte súbita. Uma parcela considerável dos pacientes não obtém controle efetivo da doença, a despeito do uso de múltiplos fármacos e doses elevadas. A hiperativação do sistema nervoso simpático constitui a base fisiopatológica para a ablação das fibras aferentes, através da aplicação de energia por radiofrequência nas artérias renais. Esse procedimento, conhecido como denervação simpática percutânea, tem se mostrado uma terapia promissora e nos últimos anos os resultados, com número limitado de pacientes, mostraram queda significativa dos níveis tensionais e do risco cardiovascular. No entanto, boa parte da redução do risco não pode ser explicada apenas pela redução da pressão arterial, surgindo questionamentos sobre os resultados dos tratamentos (uso de múltiplos fármacos/doses elevadas) e atribuindo-se eventuais falhas da medicação sobre propriedades vasculares independentes do efeito pressórico. As alterações vasculares da micro e macrocirculação não podem ser totalmente observadas pelas medidas periféricas, sendo necessário o entendimento da disfunção endotelial. O endotélio vascular é considerado um tecido ativo e dinâmico portanto, a disfunção deste, em casos de hipertensão arterial, contribui para o desenvolvimento da aterosclerose, promovendo trombose, rigidez arterial e redução da regulação do tônus e fluxo arteriais. A identificação da endotelina como um vasoconstritor e a descoberta da sua liberação a partir do endotélio vascular sugeriu seu envolvimento na patogênese da hipertensão e da doença vascular, sendo atualmente o agente vasoconstritor mais potente já identificado. Avaliou-se a redução dos níveis pressóricos através da denervação simpática em um hipertenso resistente e correlacionou-se seus níveis de endotelina com pacientes portadores de doenças cardiovasculares. Não houve complicações, sendo que aos 18 meses a queda média foi de 18mmHg na PAS da MAPA 24h e 19mmHg na pressão central. Estes dois métodos mostraram-se iguais na aferição do sucesso terapêutico. Níveis maiores de endotelina estiveram presentes na doença cardiovascular, podendo ser um novo biomarcador de lesão endotelial na doença cardíaca.