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

Perivascular adipose (PVAT) has been hypothesized to influence arterial health, where an excess can lead to pathogenesis of atherosclerosis and other arterial pathologies. A novel assessment of carotid PVAT is the use of carotid extra media thickness (EMT) ultrasonography. Currently, there is a lack of research to demonstrate the relationship between carotid EMT and existing measures of arterial health, notably, central pulse wave velocity, and carotid distensibility and intimal media thickness. In the current cross sectional study, 81 participants of younger recreationally active (ages 23.2 ± 2.5 years), younger sedentary (ages 26.4 ± 7.2 years), older healthy (ages 70.3 ± 5.4 years) and older adults with coronary artery disease (CAD) (ages 67.9 ± 8.7 years) were recruited. Resting measures of central arterial stiffness was examined through the assessment of aPWV, while measures of local carotid stiffness were examined through carotid distensibility. Aortic PWV was calculated using an accepted direct distance method (80% of carotid to femoral direct distance) and time difference between the feet of the carotid and femoral waveforms. Carotid intima-media thickness (IMT), a measure of the inner arterial walls, and carotid extra media thickness (EMT), a measure of carotid PVAT, were assessed through B-mode ultrasound images and a semi-automated edge tracking software. Carotid EMT, IMT, and aPWV were significantly greater in older adults than in younger adults (p < 0.05). No difference in carotid EMT was found between younger recreationally active (0.47 ± .08 mm) and sedentary adults (0.46 ± .06 mm). There were also no differences in carotid EMT between the older healthy (0.58 ± .06 mm) and older adults with CAD (0.54 ± 0.08 mm). Carotid EMT was also significantly correlated with age (r =0 .500), waist circumference (r = 0.521), aPWV (r =0.431), carotid distensibility (r = -0.364 and IMT (r = 0.404). Despite significant correlations, carotid EMT was not an independent predictor of aPWV, carotid distensibility and IMT. Because of the lack of predictive power in measures of arterial stiffness and carotid IMT, there is a potential that carotid EMT may be an independent vascular disease marker. Future investigations should involve carotid EMT in longitudinal studies to evaluate the potential marker for a more comprehensive cardiovascular risk assessment. / Thesis / Master of Science (MSc)

INTRODUÇÃO: A Hipersensibilidade do seio carotídeo (HSC) é a exacerbação do reflexo normal e foi definida como ocorrência de pausa ventricular 3 segundos ou redução da pressão arterial sistólica (PAS) 50 mmHg em resposta à massagem do seio carotídeo (MSC). Fenômeno relacionado à idade, raramente diagnosticado em pacientes com menos de 50 anos, tem recebido especial atenção como causa de síncope e quedas inexplicadas nos idosos, nas últimas décadas, com relatos de taxas de prevalências superiores a 45%. Entretanto, ainda não estão claras as implicações diagnósticas da HSC na síncope, com resultados controversos na literatura. OBJETIVOS: Determinar a prevalência da HSC em pacientes com sintomas de síncope e pré-síncope e comparar com indivíduos assintomáticos. Correlacionar a resposta à MSC com a rigidez aórtica e os parâmetros anatômicos e funcionais carotídeos. MÉTODOS: Foram avaliados em estudo prospectivo 99 pcts sintomáticos, com síncope ou pré-síncope a esclarecer (idade média de 69 anos, 41,4% homens), e 66 pcts assintomáticos para controle (idade média de 73 anos, 34,8% homens). Excluíram-se pacientes com cardiopatia estrutural ou com contraindicações para MSC. A MSC foi realizada no ponto com maior impulsão carotídea por 5 segundos, com o registro contínuo e não invasivo da pressão arterial (PA) e eletrocardiograma, com o paciente em postura ortostática a 70º. Foram consideradas respostas anormais: cardioinibitória (CI): assistolia 3 segundos e vasodepressora (VD): redução da PAS 50 mmHg. O índice da rigidez arterial foi obtido por meio de medida da velocidade de onda de pulso carotídeo-femoral (VOP). As características anatômicas e funcionais da carótida foram determinadas por medidas de diâmetro, espessura íntima-média carotídea (EIMC) e índice de distensibilidade. RESULTADOS: Não foram constatadas diferenças nas respostas obtidas na MSC entre os grupos, com 67,7% e 60,6% de respostas fisiológicas; 24,2% e 25,8% de respostas CI; 8,1% e 13,6% de respostas VD em grupo sintomáticos e assintomáticos, respectivamente (p=0,466). Não foram observadas correlações entre a resposta à MSC, tanto com a VOP como com a EMIC, a distensibilidade e o diâmetro carotídeo. CONCLUSÕES: 1- A prevalência de HSC e resposta hemodinâmica à MSC em pacientes com sintomas de síncope e pré-síncope foram semelhantes a pacientes assintomáticos provenientes da mesma instituição, com características clínicas semelhantes. 2- Não foi observada correlação significativa entre a rigidez arterial, medida por meio da VOP, EIMC, distensibilidade e diâmetro carotídeo e a resposta à MSC / The carotid sinus hypersensitivity (CSH) is the exaggeration of the normal reflex and was defined by occurrence of asystole 3 seconds or fall in systolic BP 50 mmHg in response to carotid sinus massage (CSM). Phenomenon related to age, rarely diagnosed in patients younger than 50 years, has gained importance as a cause of syncope and unexplained falls in the elderly in recent decades with reported prevalence rates above 45%. However, the correlation between CSH and syncope etiology is still controversial. OBJECTIVE: To determine the prevalence of CSH in patients with syncope and near syncope of unknown origin and compare with asymptomatic individuals; to evaluate the correlation between CSM responses and arterial stiffness. METHODS: We studied prospectively 99 symptomatic pts with syncope or near syncope (mean age 69 years, 41.4% men) and 66 asymptomatic controls (mean age 73 years, 34.8% men). Patients with significant structural heart disease or with contraindications to CSM were excluded. The CSM was performed at the point with maximal carotid pulsation, for 5 seconds with continuous and noninvasive blood pressure and electrocardiogram recording at 70° in upright posture. Were considered abnormal responses: cardioinhibitory (CI): asystole 3 seconds and vasodepressor (VD): decrease in systolic BP 50 mmHg. The aortic stiffness was determined by aortic pulse wave velocity (PWV). The anatomical and functional characteristics of the carotid were determined by measurements of diameter, intima-media thickness (IMT) and distensibility index. RESULTS: There were no differences in the responses obtained in the CSM between the groups, being 67.7 % and 60.6% physiological responses, 24.2% and 25.8% CI responses and 8.1% and 13.6% VD responses in symptomatic and asymptomatic groups, respectively (p=0.466). There were no correlations between response to the CSM with VOP, IMT, carotid diameter and distensibility. CONCLUSIONS: The prevalence of CSH in patients with symptoms of syncope and near syncope was similar to asymptomatic patients from the same institution with similar clinical characteristics. There was no significant correlation between arterial stiffness, measured by PWV, IMT, carotid diameter and distensibility with the response to CSM

INTRODUÇÃO: A Hipersensibilidade do seio carotídeo (HSC) é a exacerbação do reflexo normal e foi definida como ocorrência de pausa ventricular 3 segundos ou redução da pressão arterial sistólica (PAS) 50 mmHg em resposta à massagem do seio carotídeo (MSC). Fenômeno relacionado à idade, raramente diagnosticado em pacientes com menos de 50 anos, tem recebido especial atenção como causa de síncope e quedas inexplicadas nos idosos, nas últimas décadas, com relatos de taxas de prevalências superiores a 45%. Entretanto, ainda não estão claras as implicações diagnósticas da HSC na síncope, com resultados controversos na literatura. OBJETIVOS: Determinar a prevalência da HSC em pacientes com sintomas de síncope e pré-síncope e comparar com indivíduos assintomáticos. Correlacionar a resposta à MSC com a rigidez aórtica e os parâmetros anatômicos e funcionais carotídeos. MÉTODOS: Foram avaliados em estudo prospectivo 99 pcts sintomáticos, com síncope ou pré-síncope a esclarecer (idade média de 69 anos, 41,4% homens), e 66 pcts assintomáticos para controle (idade média de 73 anos, 34,8% homens). Excluíram-se pacientes com cardiopatia estrutural ou com contraindicações para MSC. A MSC foi realizada no ponto com maior impulsão carotídea por 5 segundos, com o registro contínuo e não invasivo da pressão arterial (PA) e eletrocardiograma, com o paciente em postura ortostática a 70º. Foram consideradas respostas anormais: cardioinibitória (CI): assistolia 3 segundos e vasodepressora (VD): redução da PAS 50 mmHg. O índice da rigidez arterial foi obtido por meio de medida da velocidade de onda de pulso carotídeo-femoral (VOP). As características anatômicas e funcionais da carótida foram determinadas por medidas de diâmetro, espessura íntima-média carotídea (EIMC) e índice de distensibilidade. RESULTADOS: Não foram constatadas diferenças nas respostas obtidas na MSC entre os grupos, com 67,7% e 60,6% de respostas fisiológicas; 24,2% e 25,8% de respostas CI; 8,1% e 13,6% de respostas VD em grupo sintomáticos e assintomáticos, respectivamente (p=0,466). Não foram observadas correlações entre a resposta à MSC, tanto com a VOP como com a EMIC, a distensibilidade e o diâmetro carotídeo. CONCLUSÕES: 1- A prevalência de HSC e resposta hemodinâmica à MSC em pacientes com sintomas de síncope e pré-síncope foram semelhantes a pacientes assintomáticos provenientes da mesma instituição, com características clínicas semelhantes. 2- Não foi observada correlação significativa entre a rigidez arterial, medida por meio da VOP, EIMC, distensibilidade e diâmetro carotídeo e a resposta à MSC / The carotid sinus hypersensitivity (CSH) is the exaggeration of the normal reflex and was defined by occurrence of asystole 3 seconds or fall in systolic BP 50 mmHg in response to carotid sinus massage (CSM). Phenomenon related to age, rarely diagnosed in patients younger than 50 years, has gained importance as a cause of syncope and unexplained falls in the elderly in recent decades with reported prevalence rates above 45%. However, the correlation between CSH and syncope etiology is still controversial. OBJECTIVE: To determine the prevalence of CSH in patients with syncope and near syncope of unknown origin and compare with asymptomatic individuals; to evaluate the correlation between CSM responses and arterial stiffness. METHODS: We studied prospectively 99 symptomatic pts with syncope or near syncope (mean age 69 years, 41.4% men) and 66 asymptomatic controls (mean age 73 years, 34.8% men). Patients with significant structural heart disease or with contraindications to CSM were excluded. The CSM was performed at the point with maximal carotid pulsation, for 5 seconds with continuous and noninvasive blood pressure and electrocardiogram recording at 70° in upright posture. Were considered abnormal responses: cardioinhibitory (CI): asystole 3 seconds and vasodepressor (VD): decrease in systolic BP 50 mmHg. The aortic stiffness was determined by aortic pulse wave velocity (PWV). The anatomical and functional characteristics of the carotid were determined by measurements of diameter, intima-media thickness (IMT) and distensibility index. RESULTS: There were no differences in the responses obtained in the CSM between the groups, being 67.7 % and 60.6% physiological responses, 24.2% and 25.8% CI responses and 8.1% and 13.6% VD responses in symptomatic and asymptomatic groups, respectively (p=0.466). There were no correlations between response to the CSM with VOP, IMT, carotid diameter and distensibility. CONCLUSIONS: The prevalence of CSH in patients with symptoms of syncope and near syncope was similar to asymptomatic patients from the same institution with similar clinical characteristics. There was no significant correlation between arterial stiffness, measured by PWV, IMT, carotid diameter and distensibility with the response to CSM