Motivation: C-reactive protein (hs-CRP) and other risk factors such as cortisol and obesity in the diagnosis of cardiovascular dysfunction (CVD) in African and Caucasian women has become increasingly imperative when one considers the escalation of hypertension among these groups. Recent studies have explored some aspects of these risk factors and the roles that they play within hypertension and possible future risk for cardiovascular disease. Hs-CRP has been associated with the increased prevalence of hypertension and obesity. Cortisol per se has also been linked with the development of both hypertension and the hypothalamic-pituitary adrenal cortex (HPA) response. Nevertheless, the exact mechanism remains rather uncertain due to conflicting outcomes of research within different ethnic groups. Several recent investigations have, however, linked hypocortisolism with both urbanisation and a subsequent increased likelihood of hypertension within African women as they have presented increased vascular blood pressure responses. Conversely, Caucasian women have displayed an increased central cardiac reactivity. The lack of data regarding the relationship between the above-mentioned parameters within both African and Caucasian women serves as the motivation for conducting this study. Objective: To investigate hs-CRP, cortisol and hypertension as contributors to the increased likelihood of cardiovascular dysfunction in both African and Caucasian women within South Africa. hs-CRP use this through whole document please Methodology: The manuscript presented in Chapter 2 has been compiled using data obtained from the POWIRS (Profiles of Obese Women with Insulin Resistance Syndrome) study. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were recruited from the North-West Province of South Africa for participation within this study. Subjects were divided into normotensive (NT) and hypertensive (HT) groups according to the mean resting cardiovascular values that were taken using a Finometer device. High-sensitivity C-reactive protein (hs-CRP) and cortisol blood serum values were determined by immunochemistry and ELISA analyses. Significant differences within each ethnic group and between each of the groups (NT and HT) were determined by analysis of covariance (ANCOVA), for anthropometric, cardiovascular, hs-CRP and cortisol variables, while adjusting for cardiovascular covariates (age, smoking and alcohol consumption). Partial correlations analyses were used to examine the relationship between hs-CRP, cortisol, anthropometric and cardiovascular parameters adjusting for cardiovascular covariates. Logistic regression analyses was used within each ethnic group to determine the relationship between anthropometric, cardiovascular, hs-CRP and cortisol as independent variables and hypertension as dependent variable. This study was approved by the Ethics Committee of the North-West University and all subjects gave informed consent in writing. For a more detailed description of the subjects, study design and analytical procedures please refer to the Materials and Methods section within Chapter 2 of this dissertation. Results and Conclusion: Both ethnic groups presented higher hs-CRP and lower cortisol levels compared to normal values. Lower waist circumference (WC) and cortisol as well as higher blood pressure (BP) and vascular values were evident in Africans compared to Caucasians. Both HT ethnic groups were older and more visceral obese compared to their NT counterparts. HT Caucasians indicated higher central adrenergic responses whilst HT Africans showed vascular adrenergicresponses. Only NT Africans had lower cortisol values than NT Caucasians but the Africans (NT and HT) responded with higher diastolic blood pressure responses compared to their Caucasian counterparts. Moreover, hs-CRP within African women significantly correlated with all BP and obesity variables whilst hs-CRP only associated with stroke volume (SV) and compliance (Cw) within HT Caucasian women. Cortisol in both ethnic groups was strongly associated with vascular BP responses. Only BP contributed to the higher prevalence of HT in both ethnic groups. In conclusion, these results suggest the possible diverse roles of HPA axis dysregulation associated with higher inflammatory responses. This happens in conjunction with cardiac and vascular responses within more obese Caucasian and especially African women, respectively. / MSc (Physiology), North-West University, Potchefstroom Campus, 2009

Motivation: C-reactive protein (hs-CRP) and other risk factors such as cortisol and obesity in the diagnosis of cardiovascular dysfunction (CVD) in African and Caucasian women has become increasingly imperative when one considers the escalation of hypertension among these groups. Recent studies have explored some aspects of these risk factors and the roles that they play within hypertension and possible future risk for cardiovascular disease. Hs-CRP has been associated with the increased prevalence of hypertension and obesity. Cortisol per se has also been linked with the development of both hypertension and the hypothalamic-pituitary adrenal cortex (HPA) response. Nevertheless, the exact mechanism remains rather uncertain due to conflicting outcomes of research within different ethnic groups. Several recent investigations have, however, linked hypocortisolism with both urbanisation and a subsequent increased likelihood of hypertension within African women as they have presented increased vascular blood pressure responses. Conversely, Caucasian women have displayed an increased central cardiac reactivity. The lack of data regarding the relationship between the above-mentioned parameters within both African and Caucasian women serves as the motivation for conducting this study. Objective: To investigate hs-CRP, cortisol and hypertension as contributors to the increased likelihood of cardiovascular dysfunction in both African and Caucasian women within South Africa. hs-CRP use this through whole document please Methodology: The manuscript presented in Chapter 2 has been compiled using data obtained from the POWIRS (Profiles of Obese Women with Insulin Resistance Syndrome) study. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were recruited from the North-West Province of South Africa for participation within this study. Subjects were divided into normotensive (NT) and hypertensive (HT) groups according to the mean resting cardiovascular values that were taken using a Finometer device. High-sensitivity C-reactive protein (hs-CRP) and cortisol blood serum values were determined by immunochemistry and ELISA analyses. Significant differences within each ethnic group and between each of the groups (NT and HT) were determined by analysis of covariance (ANCOVA), for anthropometric, cardiovascular, hs-CRP and cortisol variables, while adjusting for cardiovascular covariates (age, smoking and alcohol consumption). Partial correlations analyses were used to examine the relationship between hs-CRP, cortisol, anthropometric and cardiovascular parameters adjusting for cardiovascular covariates. Logistic regression analyses was used within each ethnic group to determine the relationship between anthropometric, cardiovascular, hs-CRP and cortisol as independent variables and hypertension as dependent variable. This study was approved by the Ethics Committee of the North-West University and all subjects gave informed consent in writing. For a more detailed description of the subjects, study design and analytical procedures please refer to the Materials and Methods section within Chapter 2 of this dissertation. Results and Conclusion: Both ethnic groups presented higher hs-CRP and lower cortisol levels compared to normal values. Lower waist circumference (WC) and cortisol as well as higher blood pressure (BP) and vascular values were evident in Africans compared to Caucasians. Both HT ethnic groups were older and more visceral obese compared to their NT counterparts. HT Caucasians indicated higher central adrenergic responses whilst HT Africans showed vascular adrenergicresponses. Only NT Africans had lower cortisol values than NT Caucasians but the Africans (NT and HT) responded with higher diastolic blood pressure responses compared to their Caucasian counterparts. Moreover, hs-CRP within African women significantly correlated with all BP and obesity variables whilst hs-CRP only associated with stroke volume (SV) and compliance (Cw) within HT Caucasian women. Cortisol in both ethnic groups was strongly associated with vascular BP responses. Only BP contributed to the higher prevalence of HT in both ethnic groups. In conclusion, these results suggest the possible diverse roles of HPA axis dysregulation associated with higher inflammatory responses. This happens in conjunction with cardiac and vascular responses within more obese Caucasian and especially African women, respectively. / MSc (Physiology), North-West University, Potchefstroom Campus, 2009

Motivation: The prevalence of cardiovascular dysfunction, especially hypertension, in Africans has increased dramatically over the past few decades. Despite considerable in~ depth studies, cardiovascular diseases remain the leading cause of morbidity and mortality. Further escalations are predicted, especially in developing countries such as South Africa, if measures are not taken to combat the trend. Numerous cardiovascular risk factors have been investigated within African-Americans as well as Caucasians. However, it is not known to what extent African-Americans and Africans from South Africa are comparable. Therefore, it is essential to investigate risk factors and their possible contributory role in the high susceptibility of cardiovascular dysfunction in the black South African population. Aim: To investigale potential risk factors and their possible involvement and association with the high prevalence of cardiovascular dysfunction within the black South African population. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of the data obtained from the cross-sectional SAfrEIC (The South African study regarding the influence of Sex, age and ethnicity on insulin sensitivity and Cardiovascular function) study. The study group included 756 asymptomatic, apparently healthy African men and women as well as Caucasian men and women, recruited from the North West Province, South Africa. Anthropometric and cardiovascular measurements were taken as well as their lipid profiles, fasting insulin levels, and uric acid and adiponectin levels. Independent t-tests, analyses of variance (ANOVA) and analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences. Partial correlations coefficients were used to show association between variables while adjusting for confounders. Multiple analyses of covariance (MANCOVA) were performed to compare variables between the groups, whilst adjusting for relevant confounders. Stepwise multiple and single regression analyses were also used to determine and confirm the most significant associations between variables. All subjects gave informed consent in writing and the Ethics Committee of the NorthWest University approved the study, The reader is referred to the "Materials and Methods" section of Chapters 2, 3 and 4 for a more elaborate description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts *Results from Chapter 2 revealed significantly lower uric acid levels for African men compared to Caucasian men, Despite these lower levels. the association between uric acid and blood pressure is more pronounced within the African men. The strong positive relationship between uric acid and blood pressure might be explained by uric acid's independent relationship with vascular resistance, Uric acid also revealed a positive association with triglycerides in both the African and Caucasian men. These results suggest that uric acid per se can act as a risk factor in the development of cardiovascular dysfunction in African men, *Results from Chapter 3 showed opposing changes in insulin secretion for African men and Caucasian men with increasing age. Whereas insulin levels increased in Caucasian men with progressive age, insulin levels in African men tended to decrease with ageing. Additionally, the insulin-blood pressure relationship within African men revealed opposite results as to what was expected. While the Caucasian men revealed a more positive association between insulin and blood pressure within the younger individuals, older individuals revealed a negative association between insulin and blood pressure, This implies that the vasoconstrictory actions of insulin seem to dominate in young individuals while the vasodilatory actions of insulin take over in older individuals, The turnaround probably acts as a counter protective mechanism against age-related cardiovascular dysfunction. On the contrary, despite decreased insulin secretion in older African men, they exhibit a more positive association between insulin and blood pressure, whereas younger subjects showed a more negative association, These results might suggest dissociation between insulin and blood pressure, Insulin per se might, therefore, not act as a risk factor, but rather the lack of insulin-mediated vasodilatory effects as observed within younger Africans. *Results from Chapter 4 contradicted the notion found in the literature that age-related increase in adiponectin levels are due to impaired renal function. Although the results from this chapter confirmed a Significant association between renal function (estimated creatinine clearance) and adiponectin levels a multiple regression model revealed insulin resistance (HOMA-IR) as the major contributor to adiponectin levels. Adiponectin levels increased with progressive ageing only in the Africans. No such change was observed for the Caucasians. This might be due to development of functional adiponectin resistance or perhaps due to a decline in pancreatic cell mass with ageing. In conclusion, the cardiovascular profile of Africans seems to be more detrimentally affected compared to Caucasians. Results from this study have elucidated on the associations and potential involvement of possible risk factors including, uric acid, insulin, C-peptide, as well as adiponectin, with regards to the high prevalence of cardiovascular dysfunction within the black South African population. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2010.

Motivation: The prevalence of cardiovascular dysfunction, especially hypertension, in Africans has increased dramatically over the past few decades. Despite considerable in~ depth studies, cardiovascular diseases remain the leading cause of morbidity and mortality. Further escalations are predicted, especially in developing countries such as South Africa, if measures are not taken to combat the trend. Numerous cardiovascular risk factors have been investigated within African-Americans as well as Caucasians. However, it is not known to what extent African-Americans and Africans from South Africa are comparable. Therefore, it is essential to investigate risk factors and their possible contributory role in the high susceptibility of cardiovascular dysfunction in the black South African population. Aim: To investigale potential risk factors and their possible involvement and association with the high prevalence of cardiovascular dysfunction within the black South African population. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of the data obtained from the cross-sectional SAfrEIC (The South African study regarding the influence of Sex, age and ethnicity on insulin sensitivity and Cardiovascular function) study. The study group included 756 asymptomatic, apparently healthy African men and women as well as Caucasian men and women, recruited from the North West Province, South Africa. Anthropometric and cardiovascular measurements were taken as well as their lipid profiles, fasting insulin levels, and uric acid and adiponectin levels. Independent t-tests, analyses of variance (ANOVA) and analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences. Partial correlations coefficients were used to show association between variables while adjusting for confounders. Multiple analyses of covariance (MANCOVA) were performed to compare variables between the groups, whilst adjusting for relevant confounders. Stepwise multiple and single regression analyses were also used to determine and confirm the most significant associations between variables. All subjects gave informed consent in writing and the Ethics Committee of the NorthWest University approved the study, The reader is referred to the "Materials and Methods" section of Chapters 2, 3 and 4 for a more elaborate description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts *Results from Chapter 2 revealed significantly lower uric acid levels for African men compared to Caucasian men, Despite these lower levels. the association between uric acid and blood pressure is more pronounced within the African men. The strong positive relationship between uric acid and blood pressure might be explained by uric acid's independent relationship with vascular resistance, Uric acid also revealed a positive association with triglycerides in both the African and Caucasian men. These results suggest that uric acid per se can act as a risk factor in the development of cardiovascular dysfunction in African men, *Results from Chapter 3 showed opposing changes in insulin secretion for African men and Caucasian men with increasing age. Whereas insulin levels increased in Caucasian men with progressive age, insulin levels in African men tended to decrease with ageing. Additionally, the insulin-blood pressure relationship within African men revealed opposite results as to what was expected. While the Caucasian men revealed a more positive association between insulin and blood pressure within the younger individuals, older individuals revealed a negative association between insulin and blood pressure, This implies that the vasoconstrictory actions of insulin seem to dominate in young individuals while the vasodilatory actions of insulin take over in older individuals, The turnaround probably acts as a counter protective mechanism against age-related cardiovascular dysfunction. On the contrary, despite decreased insulin secretion in older African men, they exhibit a more positive association between insulin and blood pressure, whereas younger subjects showed a more negative association, These results might suggest dissociation between insulin and blood pressure, Insulin per se might, therefore, not act as a risk factor, but rather the lack of insulin-mediated vasodilatory effects as observed within younger Africans. *Results from Chapter 4 contradicted the notion found in the literature that age-related increase in adiponectin levels are due to impaired renal function. Although the results from this chapter confirmed a Significant association between renal function (estimated creatinine clearance) and adiponectin levels a multiple regression model revealed insulin resistance (HOMA-IR) as the major contributor to adiponectin levels. Adiponectin levels increased with progressive ageing only in the Africans. No such change was observed for the Caucasians. This might be due to development of functional adiponectin resistance or perhaps due to a decline in pancreatic cell mass with ageing. In conclusion, the cardiovascular profile of Africans seems to be more detrimentally affected compared to Caucasians. Results from this study have elucidated on the associations and potential involvement of possible risk factors including, uric acid, insulin, C-peptide, as well as adiponectin, with regards to the high prevalence of cardiovascular dysfunction within the black South African population. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2010.