Motivation Hypertension is a pertinent health problem for urban black African men (hereafter referred to as African). Sympathetic hyperactivity and a dominant α-adrenergic response pattern have both been implicated as contributing factors to their poor cardiovascular health. In addition to the deleterious effect of neurogenic hypertension on target organs, sympathetic hyperactivity may promote the accelerated progression of left ventricular hypertrophy and structural vascular disease. Aim The overarching aim of this study is to scrutinize autonomic control of the cardiovascular system in a cohort of urban African and Caucasian men during a mental challenge. Associations were investigated between potential sympatho-vagal imbalance, blood pressure and target organ damage markers to determine cardiovascular risk in ethnic male groups. Methodology The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study involved the participation of 200 male teachers (99 African and 101 Caucasian) in the Kenneth Kaunda Education District of the North-West Province, South Africa. Of the participant group, HIV-infected (13 African) and clinically confirmed diabetics (1 Caucasian and 6 African men) were excluded from further analyses. Stratification was based on ethnicity and further as indicated through statistical interaction effects. Cardiovascular and autonomic responses were assessed during rest and on stressor exposure (cold pressor test and Stroop colour-word conflict test). Autonomic measures included baroreceptor sensitivity (BRS), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and nitric oxide metabolite (NOx) levels. Cardiovascular variables consisted of blood pressure, cardiac output, stroke volume, total peripheral resistance, heart rate, arterial compliance and ST-segment from the 12-lead electrocardiogram. Markers of target organ damage included the Cornell product (indication of left ventricular hypertrophy) and carotid intima-media thickness as indication of structural vascular disease. Means and proportions were compared by means of standard t-test and Chi-square test, respectively. Significant differences of mean cardiovascular and autonomic measures between ethnic male groups were also determined through analysis of covariance. Uni- and multivariate regression analyses were employed to demonstrate associations between target organ damage, cardiovascular and autonomic markers. Results and conclusion of each manuscript To assess autonomic nervous system and cardiovascular function as well as target organ damage, we clearly focussed on responses where our participants were challenged. Markers of autonomic responses assessed were baroreceptor sensitivity, 3-methoxy-4-hydroxyphenylglycol and nitric oxide metabolites.  The first manuscript (Chapter 2) focused on left ventricular hypertrophy as marker of target organ damage, blood pressure and baroreceptor sensitivity as marker of autonomic function. The objective was to determine whether BRS was significantly lower in African men than in the Caucasian men. Furthermore, the possible association between attenuation of BRS and increased levels of ambulatory blood pressure as well as left ventricular hypertrophy was investigated in these population groups. Results revealed that the African men had significantly lower BRS stress responses. This attenuated BRS profile was coupled with dominant α-adrenergic response patterns, which was associated with an elevation of ambulatory blood pressure. BRS attenuation (rest and stress response) was not associated with left ventricular hypertrophy. It was concluded that lower BRS, especially during stress, may pose a significant health threat for urban African men regarding the development or promotion of α-adrenergic-driven hypertension and higher cardiovascular disease risk.  The aim of the second sub-study (Chapter 3) was to investigate possible associations between structural vascular disease (carotid intima-media thickness as marker), autonomic function (MHPG as marker) and nocturnal blood pressure in the African and Caucasian men. Results showed a higher prevalence of nocturnal hypertension in the African men, with night-time blood pressure significantly higher compared to the Caucasian men. In the African and Caucasian men, carotid intima-media thickness was linearly predicted by nocturnal systolic and diastolic blood pressure respectively. In conclusion, no associations were demonstrated between MHPG and carotid intimamedia thickness or between MHPG and nocturnal blood pressure. Elevated nocturnal blood pressure evidently seems to promote structural vascular disease in this cohort of urban African and Caucasian men.  The aim of the third manuscript presented in Chapter 4, was to investigate bioavailability of NO during mental challenge (autonomic function marker) and the possible association with structural vascular disease (carotid intima-media thickness as marker). In the African men, an attenuated NOx response was demonstrated to the Stroop colour-word conflict test. After stratification into high and low NOx response groups, in the African men with a low NOx response enhanced α-adrenergic with significant STsegment depression responses was demonstrated indicating reduced myocardial oxygen supply during mental stressor exposure. Only in the African men, a ST-segment depression was significantly associated with structural vascular disease. It was concluded that the African men demonstrated a vulnerable cardiovascular profile. In this cohort of African men, the significant association between structural vascular disease and myocardial ischemia may particularly indicate a possible higher risk for future cardiovascular events. General conclusion Through the assessment of autonomic and cardiovascular responses a possible higher cardiovascular risk was demonstrated in the African men. In this cohort sympathetic hyperactivity was evident, coupled with dominant vascular response patterns and reduced myocardial oxygen supply during mental stress exposure. Based on these findings, this population group’s risk for accelerated target organ damage, as well as for future cardiovascular events, appear significantly higher than those of the Caucasian male cohort. / Thesis (PhD (Physiology))--North-West University, Potchefstroom Campus, 2013.

Motivation Hypertension is a pertinent health problem for urban black African men (hereafter referred to as African). Sympathetic hyperactivity and a dominant α-adrenergic response pattern have both been implicated as contributing factors to their poor cardiovascular health. In addition to the deleterious effect of neurogenic hypertension on target organs, sympathetic hyperactivity may promote the accelerated progression of left ventricular hypertrophy and structural vascular disease. Aim The overarching aim of this study is to scrutinize autonomic control of the cardiovascular system in a cohort of urban African and Caucasian men during a mental challenge. Associations were investigated between potential sympatho-vagal imbalance, blood pressure and target organ damage markers to determine cardiovascular risk in ethnic male groups. Methodology The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study involved the participation of 200 male teachers (99 African and 101 Caucasian) in the Kenneth Kaunda Education District of the North-West Province, South Africa. Of the participant group, HIV-infected (13 African) and clinically confirmed diabetics (1 Caucasian and 6 African men) were excluded from further analyses. Stratification was based on ethnicity and further as indicated through statistical interaction effects. Cardiovascular and autonomic responses were assessed during rest and on stressor exposure (cold pressor test and Stroop colour-word conflict test). Autonomic measures included baroreceptor sensitivity (BRS), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and nitric oxide metabolite (NOx) levels. Cardiovascular variables consisted of blood pressure, cardiac output, stroke volume, total peripheral resistance, heart rate, arterial compliance and ST-segment from the 12-lead electrocardiogram. Markers of target organ damage included the Cornell product (indication of left ventricular hypertrophy) and carotid intima-media thickness as indication of structural vascular disease. Means and proportions were compared by means of standard t-test and Chi-square test, respectively. Significant differences of mean cardiovascular and autonomic measures between ethnic male groups were also determined through analysis of covariance. Uni- and multivariate regression analyses were employed to demonstrate associations between target organ damage, cardiovascular and autonomic markers. Results and conclusion of each manuscript To assess autonomic nervous system and cardiovascular function as well as target organ damage, we clearly focussed on responses where our participants were challenged. Markers of autonomic responses assessed were baroreceptor sensitivity, 3-methoxy-4-hydroxyphenylglycol and nitric oxide metabolites.  The first manuscript (Chapter 2) focused on left ventricular hypertrophy as marker of target organ damage, blood pressure and baroreceptor sensitivity as marker of autonomic function. The objective was to determine whether BRS was significantly lower in African men than in the Caucasian men. Furthermore, the possible association between attenuation of BRS and increased levels of ambulatory blood pressure as well as left ventricular hypertrophy was investigated in these population groups. Results revealed that the African men had significantly lower BRS stress responses. This attenuated BRS profile was coupled with dominant α-adrenergic response patterns, which was associated with an elevation of ambulatory blood pressure. BRS attenuation (rest and stress response) was not associated with left ventricular hypertrophy. It was concluded that lower BRS, especially during stress, may pose a significant health threat for urban African men regarding the development or promotion of α-adrenergic-driven hypertension and higher cardiovascular disease risk.  The aim of the second sub-study (Chapter 3) was to investigate possible associations between structural vascular disease (carotid intima-media thickness as marker), autonomic function (MHPG as marker) and nocturnal blood pressure in the African and Caucasian men. Results showed a higher prevalence of nocturnal hypertension in the African men, with night-time blood pressure significantly higher compared to the Caucasian men. In the African and Caucasian men, carotid intima-media thickness was linearly predicted by nocturnal systolic and diastolic blood pressure respectively. In conclusion, no associations were demonstrated between MHPG and carotid intimamedia thickness or between MHPG and nocturnal blood pressure. Elevated nocturnal blood pressure evidently seems to promote structural vascular disease in this cohort of urban African and Caucasian men.  The aim of the third manuscript presented in Chapter 4, was to investigate bioavailability of NO during mental challenge (autonomic function marker) and the possible association with structural vascular disease (carotid intima-media thickness as marker). In the African men, an attenuated NOx response was demonstrated to the Stroop colour-word conflict test. After stratification into high and low NOx response groups, in the African men with a low NOx response enhanced α-adrenergic with significant STsegment depression responses was demonstrated indicating reduced myocardial oxygen supply during mental stressor exposure. Only in the African men, a ST-segment depression was significantly associated with structural vascular disease. It was concluded that the African men demonstrated a vulnerable cardiovascular profile. In this cohort of African men, the significant association between structural vascular disease and myocardial ischemia may particularly indicate a possible higher risk for future cardiovascular events. General conclusion Through the assessment of autonomic and cardiovascular responses a possible higher cardiovascular risk was demonstrated in the African men. In this cohort sympathetic hyperactivity was evident, coupled with dominant vascular response patterns and reduced myocardial oxygen supply during mental stress exposure. Based on these findings, this population group’s risk for accelerated target organ damage, as well as for future cardiovascular events, appear significantly higher than those of the Caucasian male cohort. / Thesis (PhD (Physiology))--North-West University, Potchefstroom Campus, 2013.

Motivation Soluble urokinase plasminogen activator receptor (suPAR) is a known inflammatory marker, which is found in various body fluids. SuPAR reflects the immune and pro–inflammatory status of patients caused by HIV and tuberculosis, amongst others. However, recent studies have shown that suPAR is related to cardiovascular function. The cardiovascular health of the black South African population is a major health concern as this group suffers mostly from hypertension and stroke, leading to an alarming increase in cardiovascular morbidity and mortality. SuPAR may be able to contribute to early detection and prevention of cardiovascular diseases. No studies regarding the associations of suPAR with cardiovascular function have been investigated on black South Africans. Objectives To investigate suPAR as a possible marker of cardiovascular function in African and Caucasian men and women, by determining possible gender and ethnic–specific associations of suPAR with cardiovascular function. Methodology There were 207 African and 314 Caucasian men and women (aged 20–79 yrs.) included in this study. High–sensitivity C–reactive protein, glucose, lipids and creatinine were determined in fasting serum and suPAR was analyzed in plasma samples. Blood pressure was measured using the OMRON apparatus (HEM–747), with a 5–min rest interval between measurements. The Finometer device was used to determine the Windkessel compliance and the carotid dorsalis–pedis pulse wave velocity (PWV) was measured with the Complior (SP acquisition system) on the left side of each subject in the supine position. The means, adjusted means and proportions were compared between the groups by using independent t–tests, analysis of co–variance and the chi–square test, respectively. Associations were investigated between cardiovascular variables and suPAR using single and multiple regression analyses with either pulse wave velocity, systolic blood pressure, diastolic blood pressure or Windkessel compliance as dependent variable. Covariates included were age, body mass index, smoking, alcohol use, physical activity, glucose and high–density lipoprotein cholesterol. Results and conclusion SuPAR levels were significantly higher in Africans (P<0.001) compared to Caucasians. After adjusting for body mass index, suPAR increased significantly with age in all groups, except for African women. Moreover, the suPAR levels of African men and women were significantly higher than the Caucasians within each age quartile. While adjusting for age and body mass index, the cardiovascular profiles of the African and Caucasian men were less favourable compared to women, but suPAR levels were significantly higher in Caucasian women compared to men. In single regression, various measures of cardiovascular function correlated with suPAR in African men and Caucasian men and women. After adjusting for confounders the associations disappeared in Caucasian women, and remained nonsignificant in the African women. However, the association between PWV and suPAR remained significant in African men (B=0.19; P=0.030), while the association of systolic blood pressure (B=0.20; P=0.017), diastolic blood pressure (B=0.17; P=0.020) and Windkessel compliance (B=–0.14; P=0.004) with suPAR remained significant in Caucasian men. In conclusion, Africans presented higher suPAR levels compared to Caucasians, even when stratified by age. Gender specific associations indicated that suPAR was associated with arterial stiffness in African and Caucasian men only, therefore, indicating that suPAR could be a possible biomarker for predicting cardiovascular dysfunction. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2011.

Cardiovascular disease is known as one of the leading causes of mortality worldwide, where low income countries or developing countries have the highest prevalence of cardiovascular disease. One of the main reasons for this statistics is acculturation that leads to changes in behavioral lifestyle and malnutrition within these countries. Low body mass index was found to be an independent risk factor for cardiovascular disease in several studies. From literature it is found that body mass index is lower than the ideal body mass index and is associated with cardiovascular disease. According to Higashi (2003) a body mass index of 22.2 kg/m2 is associated with the lowest morbidity. If body mass index decreases to lower values than the ideal body mass index, a J–curve will be evident suggesting higher prevalence of cardiovascular disease associated with low body mass index. These findings imply that not only high body mass index but also a low body mass index may be a risk factor for cardiovascular disease, morbidity and mortality. Whether low body mass index is associated with cardiovascular risk in an African population remains unclear. Objective: The aim of this study was to investigate the possible associations of low body mass index with variables of cardiovascular function in Africans, with a low socio–economic status. Methodology: This prospective cohort study (N= 2 010) is part of the Prospective Urban and Rural Epidemiology study (PURE) conducted in the North–West Province of South Africa in 2005, where the health transition in urban and rural subjects was investigated within an apparently low socio–economic status group. Our crosssectional PURE sub–study included 496 African people from rural and urban settings, (men, N= 252 and women, N= 244) aged between 35–65 years and body mass index lower than 25 kg/m2. Subjects were sub–divided into two groups. The first group consisted of Africans with a low body mass index smaller or equal to 20 kg/m2 (men; N= 152, women; N= 94) whilst the second group consisted of Africans with a normal body mass index larger than 20 kg/m2 and smaller or equal to 25 kg/m2 (men; N= 100, women; N= 150). Systolic blood pressure and diastolic blood pressure measurements were obtained with the validated OMRON HEM–757 device. The pulse wave velocity was measured using the Complior SP device. Blood was drawn by a registered nurse from the antebrachial vein using a sterile winged infusion set and syringes. Analyses for cholesterol, high density lipoprotein, triglycerides, gamma–glutamyl transferase and high sensitive C–reactive protein were completed utilizing the Konelab 20i. Data analyses were performed using the Statistica 10 program. Statistical analyses were executed to determine significant differences between age, body mass index and lifestyle factors as well as cardiovascular related variables in the different groups. T–tests were used to determine significant differences between independent groups. ANCOVA tests were used to determine BMI group differences independent of age, smoking and alcohol consumption. Partial correlations, which were adjusted for age, smoking and alcohol consumption, determined associations between the BMI groups and cardiovascular variables. Results: Our results indicated significantly higher mean values for the African men, with low body mass index, for cardiovascular variables (Diastolic blood pressure, 88.0 ± standard deviation (SD) 13.4 mmHg; mean arterial pressure, 103.8 ± SD 14.4 mmHg and carotid–radial pulse wave velocity, 12.6 ± SD 2.47 m/s) compared to the normal body mass index group (Diastolic blood pressure, 84.2 ± SD 12.2 mmHg; mean arterial pressure, 100.0 ± SD 13.2 mmHg and carotid–radial pulse wave velocity, 11.6 ± SD 2.00 m/s). The African women with low body mass index had a significant difference for carotid–radial pulse wave velocity (11.3 ± SD 2.43 m/s) compared to the normal body mass index group (10.6 ± SD 2.10 m/s). In African men, after the variables were adjusted for age, smoking and alcohol consumption, we revealed that diastolic blood pressure (88.0 with confidence interval (CI) [86.0– 90.0] mmHg) and carotid–radial pulse wave velocity (12.5 with CI [12.1–12.9] m/s) remained significant higher in the low body mass index group. Additionally, carotidradial pulse wave velocity was negatively associated with body mass index in African men. In the low body mass index group, Pearson and partial correlations of r= – 0.204; p= 0.012 and r= –0.200; p= 0.020 were found respectively in carotid–radial pulse wave velocity. Furthermore, in our unadjusted scatter plot with body mass index versus pulse wave velocity this negative trend of increasing carotid–radial pulse wave velocity with decreasing body mass index was noticeable in both African men and women. Even when carotid–radial pulse wave velocity was adjusted for age, smoking, alcohol consumption, mean arterial pressure and heart rate, a J–curve between carotid–radial pulse wave velocity and body mass index was still evident. Conclusion: A detrimental effect of low body mass index is evident on cardiovascular function in Africans. If body mass index decreases from the optimum value of 22.2 kg/m2 to lower values, a J–curve is evident between body mass index and cardiovascular variables suggesting higher prevalence of cardiovascular disease associated with low body mass index. In our sub–study the carotid–radial pulse wave velocity increases significantly in African men with low body mass index, thus supporting the theory that stiffening of the arteries is evident in Africans with a low body mass index. Low body mass index may contribute to the high prevalence of cardiovascular disease mortality within developing countries and therefore, increase the risk for cardiovascular disease. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

Motivation Soluble urokinase plasminogen activator receptor (suPAR) is a known inflammatory marker, which is found in various body fluids. SuPAR reflects the immune and pro–inflammatory status of patients caused by HIV and tuberculosis, amongst others. However, recent studies have shown that suPAR is related to cardiovascular function. The cardiovascular health of the black South African population is a major health concern as this group suffers mostly from hypertension and stroke, leading to an alarming increase in cardiovascular morbidity and mortality. SuPAR may be able to contribute to early detection and prevention of cardiovascular diseases. No studies regarding the associations of suPAR with cardiovascular function have been investigated on black South Africans. Objectives To investigate suPAR as a possible marker of cardiovascular function in African and Caucasian men and women, by determining possible gender and ethnic–specific associations of suPAR with cardiovascular function. Methodology There were 207 African and 314 Caucasian men and women (aged 20–79 yrs.) included in this study. High–sensitivity C–reactive protein, glucose, lipids and creatinine were determined in fasting serum and suPAR was analyzed in plasma samples. Blood pressure was measured using the OMRON apparatus (HEM–747), with a 5–min rest interval between measurements. The Finometer device was used to determine the Windkessel compliance and the carotid dorsalis–pedis pulse wave velocity (PWV) was measured with the Complior (SP acquisition system) on the left side of each subject in the supine position. The means, adjusted means and proportions were compared between the groups by using independent t–tests, analysis of co–variance and the chi–square test, respectively. Associations were investigated between cardiovascular variables and suPAR using single and multiple regression analyses with either pulse wave velocity, systolic blood pressure, diastolic blood pressure or Windkessel compliance as dependent variable. Covariates included were age, body mass index, smoking, alcohol use, physical activity, glucose and high–density lipoprotein cholesterol. Results and conclusion SuPAR levels were significantly higher in Africans (P<0.001) compared to Caucasians. After adjusting for body mass index, suPAR increased significantly with age in all groups, except for African women. Moreover, the suPAR levels of African men and women were significantly higher than the Caucasians within each age quartile. While adjusting for age and body mass index, the cardiovascular profiles of the African and Caucasian men were less favourable compared to women, but suPAR levels were significantly higher in Caucasian women compared to men. In single regression, various measures of cardiovascular function correlated with suPAR in African men and Caucasian men and women. After adjusting for confounders the associations disappeared in Caucasian women, and remained nonsignificant in the African women. However, the association between PWV and suPAR remained significant in African men (B=0.19; P=0.030), while the association of systolic blood pressure (B=0.20; P=0.017), diastolic blood pressure (B=0.17; P=0.020) and Windkessel compliance (B=–0.14; P=0.004) with suPAR remained significant in Caucasian men. In conclusion, Africans presented higher suPAR levels compared to Caucasians, even when stratified by age. Gender specific associations indicated that suPAR was associated with arterial stiffness in African and Caucasian men only, therefore, indicating that suPAR could be a possible biomarker for predicting cardiovascular dysfunction. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2011.

Cardiovascular disease is known as one of the leading causes of mortality worldwide, where low income countries or developing countries have the highest prevalence of cardiovascular disease. One of the main reasons for this statistics is acculturation that leads to changes in behavioral lifestyle and malnutrition within these countries. Low body mass index was found to be an independent risk factor for cardiovascular disease in several studies. From literature it is found that body mass index is lower than the ideal body mass index and is associated with cardiovascular disease. According to Higashi (2003) a body mass index of 22.2 kg/m2 is associated with the lowest morbidity. If body mass index decreases to lower values than the ideal body mass index, a J–curve will be evident suggesting higher prevalence of cardiovascular disease associated with low body mass index. These findings imply that not only high body mass index but also a low body mass index may be a risk factor for cardiovascular disease, morbidity and mortality. Whether low body mass index is associated with cardiovascular risk in an African population remains unclear. Objective: The aim of this study was to investigate the possible associations of low body mass index with variables of cardiovascular function in Africans, with a low socio–economic status. Methodology: This prospective cohort study (N= 2 010) is part of the Prospective Urban and Rural Epidemiology study (PURE) conducted in the North–West Province of South Africa in 2005, where the health transition in urban and rural subjects was investigated within an apparently low socio–economic status group. Our crosssectional PURE sub–study included 496 African people from rural and urban settings, (men, N= 252 and women, N= 244) aged between 35–65 years and body mass index lower than 25 kg/m2. Subjects were sub–divided into two groups. The first group consisted of Africans with a low body mass index smaller or equal to 20 kg/m2 (men; N= 152, women; N= 94) whilst the second group consisted of Africans with a normal body mass index larger than 20 kg/m2 and smaller or equal to 25 kg/m2 (men; N= 100, women; N= 150). Systolic blood pressure and diastolic blood pressure measurements were obtained with the validated OMRON HEM–757 device. The pulse wave velocity was measured using the Complior SP device. Blood was drawn by a registered nurse from the antebrachial vein using a sterile winged infusion set and syringes. Analyses for cholesterol, high density lipoprotein, triglycerides, gamma–glutamyl transferase and high sensitive C–reactive protein were completed utilizing the Konelab 20i. Data analyses were performed using the Statistica 10 program. Statistical analyses were executed to determine significant differences between age, body mass index and lifestyle factors as well as cardiovascular related variables in the different groups. T–tests were used to determine significant differences between independent groups. ANCOVA tests were used to determine BMI group differences independent of age, smoking and alcohol consumption. Partial correlations, which were adjusted for age, smoking and alcohol consumption, determined associations between the BMI groups and cardiovascular variables. Results: Our results indicated significantly higher mean values for the African men, with low body mass index, for cardiovascular variables (Diastolic blood pressure, 88.0 ± standard deviation (SD) 13.4 mmHg; mean arterial pressure, 103.8 ± SD 14.4 mmHg and carotid–radial pulse wave velocity, 12.6 ± SD 2.47 m/s) compared to the normal body mass index group (Diastolic blood pressure, 84.2 ± SD 12.2 mmHg; mean arterial pressure, 100.0 ± SD 13.2 mmHg and carotid–radial pulse wave velocity, 11.6 ± SD 2.00 m/s). The African women with low body mass index had a significant difference for carotid–radial pulse wave velocity (11.3 ± SD 2.43 m/s) compared to the normal body mass index group (10.6 ± SD 2.10 m/s). In African men, after the variables were adjusted for age, smoking and alcohol consumption, we revealed that diastolic blood pressure (88.0 with confidence interval (CI) [86.0– 90.0] mmHg) and carotid–radial pulse wave velocity (12.5 with CI [12.1–12.9] m/s) remained significant higher in the low body mass index group. Additionally, carotidradial pulse wave velocity was negatively associated with body mass index in African men. In the low body mass index group, Pearson and partial correlations of r= – 0.204; p= 0.012 and r= –0.200; p= 0.020 were found respectively in carotid–radial pulse wave velocity. Furthermore, in our unadjusted scatter plot with body mass index versus pulse wave velocity this negative trend of increasing carotid–radial pulse wave velocity with decreasing body mass index was noticeable in both African men and women. Even when carotid–radial pulse wave velocity was adjusted for age, smoking, alcohol consumption, mean arterial pressure and heart rate, a J–curve between carotid–radial pulse wave velocity and body mass index was still evident. Conclusion: A detrimental effect of low body mass index is evident on cardiovascular function in Africans. If body mass index decreases from the optimum value of 22.2 kg/m2 to lower values, a J–curve is evident between body mass index and cardiovascular variables suggesting higher prevalence of cardiovascular disease associated with low body mass index. In our sub–study the carotid–radial pulse wave velocity increases significantly in African men with low body mass index, thus supporting the theory that stiffening of the arteries is evident in Africans with a low body mass index. Low body mass index may contribute to the high prevalence of cardiovascular disease mortality within developing countries and therefore, increase the risk for cardiovascular disease. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

The female athlete triad (FAT or the TRIAD) is a complex syndrome arising from associations among the trio of energy availability (EA), menstrual function (MF) and bone mineral density (BMD) along their respective continuums from health to disease state. It has been recognized that women whose energy intake (EI) does not meet the energy requirements for physiological functions subsequent to participation in exercise and physical activity could have low EA. In the TRIAD, low EA, an initiator in menstrual dysfunction (MD) and concomitant hypoestrogenism, indirectly results in low BMD. Therefore, the purpose of this study was to: (i) establish the status of EA, MF and BMD among elite Kenyan female athletes and non-athletes, (ii) explore associations between EA and MF in elite Kenyan female athletes and non-athletes, (iii) determine the relationships of EA and MF to BMD in elite Kenyan female athletes and non-athletes, and (iv) to determine the profile of the female athlete triad in elite Kenyan distance athletes and in non-athletes. Measurements of EA, MF and BMD were undertaken in 39 female participants (Middle distance athletes =12, Long distance athletes=13, Non-athletes=14). Energy intake minus exercise energy expenditure (EEE) and the remnant normalized to fat free mass (FFM) determined EA. Energy availability was determined through weight of all food and liquid consumed over three consecutive days. Exercise energy expenditure was determined after isolating and deducting energy expended in exercise or physical activity above lifestyle level from the total energy expenditure output as measured by Actigraph GT3X+. Fat free mass and BMD were assessed using dual energy x-ray absorptiometry (DXA). A nine-month daily temperature-menstrual diary was used to evaluate menstrual status. In addition, since psychological eating behaviour practice (EBP) contributes to low EA, the Eating Disorder Examination Questionnaire (EDE-Q) was used to determine presence of such practice among the participants and their relationship to EA. Overall, EA below 45 kcal.kgFFM-1.d-1 was found in 61.53% of the participants (athletes=28.07±11.45kcal.kgFFM-1.d-1, non-athletes=56.97±21.38kcal.kgFMM-1.d-1). The ANOVA showed that there was a significant difference (p<0.001) in EA among the long and middle distance runners and non-athletes; and the Tukey‘s HSD revealed that the source of the difference were the non-athletes. Results of the EDE-Q showed almost negligible presence of psychopathological eating behaviour practice among the Kenyan participants. None of the TRIAD components showed significant relationship with EBP. Results of MF showed that whereas none of the athletes presented with amenorrhea, oligomenorrhea was present among 40% athletes and 14.3% non-athletes, and amenorrhea among 14.3% non-athletes. However, there was no significant difference between athletes and non-athletes in MF. Low BMD was seen in 76% of the athletes and among 86% of the non-athletes. The analysis did not show significant difference in BMD Z-scores between athletes and non-athletes. The analysis did not show any significant association between EA and MF among the participants. The only significant relation of EA to any BMD dimension measured was between EA and total BMD in the long distance runners (r=0.560; p=.046). Significant relationship (rho=0.497; p=.001) was found between MF and BMD Z-scores among the athletes with middle distance highlighting the relationship further (rho=0.632; p=.027). Overall, the binary logistic regression revealed that MF did not predict BMD (OR=4.07, 95% CI, 0.8-20.7, p=.091). Overall, 10% of the participants (athletes=4, long distance athletes =3, middle distance athletes=1, non-athletes=0) showed simultaneous presence of all three components of the TRIAD. The independent sample t-test showed a significant difference (t=5.860; p=<.001) in the prevalence of the TRIAD between athletes and non-athletes. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2014

The female athlete triad (FAT or the TRIAD) is a complex syndrome arising from associations among the trio of energy availability (EA), menstrual function (MF) and bone mineral density (BMD) along their respective continuums from health to disease state. It has been recognized that women whose energy intake (EI) does not meet the energy requirements for physiological functions subsequent to participation in exercise and physical activity could have low EA. In the TRIAD, low EA, an initiator in menstrual dysfunction (MD) and concomitant hypoestrogenism, indirectly results in low BMD. Therefore, the purpose of this study was to: (i) establish the status of EA, MF and BMD among elite Kenyan female athletes and non-athletes, (ii) explore associations between EA and MF in elite Kenyan female athletes and non-athletes, (iii) determine the relationships of EA and MF to BMD in elite Kenyan female athletes and non-athletes, and (iv) to determine the profile of the female athlete triad in elite Kenyan distance athletes and in non-athletes. Measurements of EA, MF and BMD were undertaken in 39 female participants (Middle distance athletes =12, Long distance athletes=13, Non-athletes=14). Energy intake minus exercise energy expenditure (EEE) and the remnant normalized to fat free mass (FFM) determined EA. Energy availability was determined through weight of all food and liquid consumed over three consecutive days. Exercise energy expenditure was determined after isolating and deducting energy expended in exercise or physical activity above lifestyle level from the total energy expenditure output as measured by Actigraph GT3X+. Fat free mass and BMD were assessed using dual energy x-ray absorptiometry (DXA). A nine-month daily temperature-menstrual diary was used to evaluate menstrual status. In addition, since psychological eating behaviour practice (EBP) contributes to low EA, the Eating Disorder Examination Questionnaire (EDE-Q) was used to determine presence of such practice among the participants and their relationship to EA. Overall, EA below 45 kcal.kgFFM-1.d-1 was found in 61.53% of the participants (athletes=28.07±11.45kcal.kgFFM-1.d-1, non-athletes=56.97±21.38kcal.kgFMM-1.d-1). The ANOVA showed that there was a significant difference (p<0.001) in EA among the long and middle distance runners and non-athletes; and the Tukey‘s HSD revealed that the source of the difference were the non-athletes. Results of the EDE-Q showed almost negligible presence of psychopathological eating behaviour practice among the Kenyan participants. None of the TRIAD components showed significant relationship with EBP. Results of MF showed that whereas none of the athletes presented with amenorrhea, oligomenorrhea was present among 40% athletes and 14.3% non-athletes, and amenorrhea among 14.3% non-athletes. However, there was no significant difference between athletes and non-athletes in MF. Low BMD was seen in 76% of the athletes and among 86% of the non-athletes. The analysis did not show significant difference in BMD Z-scores between athletes and non-athletes. The analysis did not show any significant association between EA and MF among the participants. The only significant relation of EA to any BMD dimension measured was between EA and total BMD in the long distance runners (r=0.560; p=.046). Significant relationship (rho=0.497; p=.001) was found between MF and BMD Z-scores among the athletes with middle distance highlighting the relationship further (rho=0.632; p=.027). Overall, the binary logistic regression revealed that MF did not predict BMD (OR=4.07, 95% CI, 0.8-20.7, p=.091). Overall, 10% of the participants (athletes=4, long distance athletes =3, middle distance athletes=1, non-athletes=0) showed simultaneous presence of all three components of the TRIAD. The independent sample t-test showed a significant difference (t=5.860; p=<.001) in the prevalence of the TRIAD between athletes and non-athletes. / PhD (Human Movement Science), North-West University, Potchefstroom Campus, 2014

Motivation - Depression is a mental disorder that has been associated with cardiovascular morbidity and mortality in the Western world. Cardiometablic mechanisms have been implicated as possible intermediating factors in the relationship between depressive symptoms and cardiovascular disease; however this has not yet been determined in black Africans (hereafter referred to as Africans). Aim - The overarching aim of this study was to investigate the relationship between depressive symptoms and cardiometabolic risk. We therefore aimed to assess cardiometabolic function, neuroendocrine responses, inflammatory and haemostatic markers in Africans with depressive symptoms compared to those without symptoms of depression. Methodology - Manuscripts presented in Chapter 2, 3 and 4 utilised data from the cross-sectional, target population multi-disciplinary “Sympathetic activity and Ambulatory Blood Pressure in Africans” (SABPA) study. The participants comprised of 200 African teachers from the Dr Kenneth Kaunda District in North-West province, South Africa. As cardiovascular disease is compromised by a positive HIV status, 19 participants were excluded from further statistical analysis. Stratification was based on the Patient Health Questionnaire 9-item (PHQ-9), which has been validated in a sub-Saharan African setting. PHQ-9 scores > 10 were used to classify participants as having signs of depressive symptoms. Subjects were further stratified by gender (Manuscript 1 and 3) and cortisol responses (Manuscript 2). Cardiometabolic health measures included 24-hour blood pressure, metabolic syndrome markers, neuroendocrine markers [cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG)], left ventricular hypertrophy (LVH),inflammatory and haemostatic markers (fibrinogen, C-reactive protein, plasminogen activator inhibitor-1 and D-dimer). Resting 12-lead ECG Cornell Product-Left ventricular hypertrophy (CP-LVH) was measured as a marker of target end-organ damage and cardiovascular dysfunction (Manuscript 1 and 2). Means and prevalence were computed through t-test and Chi-square analysis respectively. Significant differences of mean cardiometabolic measures between depressive symptom status groups were also determined by analysis of covariance (adjusted for traditional cardiovascular risk factors and additional factors as specific per manuscript). Multivariate analysis was used to demonstrate associations between left ventricular hypertrophy (LVH) and cardiometabolic markers in Africans with depressive symptoms (Manuscript 1 and 2) and a logistic regression analysis were performed to examine the association between depressive symptoms and inflammatory/haemostatic factors (Manuscript 3). All subjects who participated gave informed consent, the study was approved by the Ethics Committee of North-West University (NWU-0003607S6), in accordance with the principles outlined by the World Medical Association Declaration of Helsinki of 1975 (revised 2008). Results and conclusions of the individual manuscripts - The aim of the study was to investigate the associations between depressive symptoms and cardiometabolic function including cardiovascular dysfunction. Markers of cardiometabolic function assessed were 24 hour blood pressure measurements, metabolic syndrome markers, neuroendocrine markers [cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG)], inflammatory and haemostatic variables (fibrinogen, C-reactive protein, plasminogen activator inhibitor-1 and D-dimer). Manuscript 1, focused on LVH as a marker of cardiovascular dysfunction and metabolic syndrome components as markers of cardiometabolic function. The aim of the study was to assess the associations between LVH and metabolic syndrome (MetS) risk markers in participants with and without depressive symptoms. Results revealed that in African men with depressive symptoms the most significant determinants of LVH were systolic blood pressure (SBP) and the percentage glycosylated haemoglobin (HbA1c). While in African women (with depressive symptoms), this association was determined by low high-density lipoprotein (HDL-cholesterol). The study concluded that in black African men, independent of depressive symptoms, cardiometabolic factors (namely SBP and HbA1c) may be the driving significant factors in the development of cardiovascular diseases. Furthermore, the data showed that depressive symptoms in African women were associated with a measure of target end organ damage, and that this association was driven by a metabolic factor. Manuscript 2, the aim of this manuscript was to examine the relationship between depressive symptoms, neuroendocrine responses [with cortisol and 3-methoxy-phenylglycol (MHPG) as markers] and cardiovascular risk, i.e. LVH. The results revealed that Africans with depressive symptoms demonstrated blunted cortisol and MHPG levels in response to acute mental stress, in comparison to those without symptoms of depression. Additionally, these low cortisol and blunted MHPG responses were associated with LVH in this ethnic group. The conclusion for this manuscript was that, blunted neuroendocrine responses linked depressive symptoms and ECG left ventricular hypertrophy in Africans. When coupled to their hypertensive status, these vasoconstrictive responses (cortisol and MHPG) may underpin the increased long-term depression and vascular disease risk in urban Africans. Manuscript 3, the aim of this manuscript was to investigate the relationship between depressive symptoms and inflammatory/haemostatic markers in a cohort of urban-dwelling black African men and women. Our data demonstrated hypercoagulation vulnerability in African men with depressive symptoms. The African men with signs of depression displayed higher plasminogen activator inhibitor (PAI-1) levels and marginally elevated D-dimer levels. It was concluded that hypercoagulation may partially be the mediating factor between depressive symptoms and cardiovascular risk in African men; a situation that may be exacerbated by hyperkinetic blood pressure. In conclusion, through the assessement of cardiometabolic function and neuroendocrine responses, it seems that Africans withdepressive symptoms are at great risk for cardiovascular related morbidity and mortality, this was particulary evident in the African men (Manuscript 1 and 3). Additionally, it appears that blunted neuroendocrine responses and hypercoagulation could be seen as possible cardiovascular risk markers in Africans with depressive symptoms. / PhD (Physiology), North-West University, Potchefstroom Campus, 2014

Motivation - Depression is a mental disorder that has been associated with cardiovascular morbidity and mortality in the Western world. Cardiometablic mechanisms have been implicated as possible intermediating factors in the relationship between depressive symptoms and cardiovascular disease; however this has not yet been determined in black Africans (hereafter referred to as Africans). Aim - The overarching aim of this study was to investigate the relationship between depressive symptoms and cardiometabolic risk. We therefore aimed to assess cardiometabolic function, neuroendocrine responses, inflammatory and haemostatic markers in Africans with depressive symptoms compared to those without symptoms of depression. Methodology - Manuscripts presented in Chapter 2, 3 and 4 utilised data from the cross-sectional, target population multi-disciplinary “Sympathetic activity and Ambulatory Blood Pressure in Africans” (SABPA) study. The participants comprised of 200 African teachers from the Dr Kenneth Kaunda District in North-West province, South Africa. As cardiovascular disease is compromised by a positive HIV status, 19 participants were excluded from further statistical analysis. Stratification was based on the Patient Health Questionnaire 9-item (PHQ-9), which has been validated in a sub-Saharan African setting. PHQ-9 scores > 10 were used to classify participants as having signs of depressive symptoms. Subjects were further stratified by gender (Manuscript 1 and 3) and cortisol responses (Manuscript 2). Cardiometabolic health measures included 24-hour blood pressure, metabolic syndrome markers, neuroendocrine markers [cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG)], left ventricular hypertrophy (LVH),inflammatory and haemostatic markers (fibrinogen, C-reactive protein, plasminogen activator inhibitor-1 and D-dimer). Resting 12-lead ECG Cornell Product-Left ventricular hypertrophy (CP-LVH) was measured as a marker of target end-organ damage and cardiovascular dysfunction (Manuscript 1 and 2). Means and prevalence were computed through t-test and Chi-square analysis respectively. Significant differences of mean cardiometabolic measures between depressive symptom status groups were also determined by analysis of covariance (adjusted for traditional cardiovascular risk factors and additional factors as specific per manuscript). Multivariate analysis was used to demonstrate associations between left ventricular hypertrophy (LVH) and cardiometabolic markers in Africans with depressive symptoms (Manuscript 1 and 2) and a logistic regression analysis were performed to examine the association between depressive symptoms and inflammatory/haemostatic factors (Manuscript 3). All subjects who participated gave informed consent, the study was approved by the Ethics Committee of North-West University (NWU-0003607S6), in accordance with the principles outlined by the World Medical Association Declaration of Helsinki of 1975 (revised 2008). Results and conclusions of the individual manuscripts - The aim of the study was to investigate the associations between depressive symptoms and cardiometabolic function including cardiovascular dysfunction. Markers of cardiometabolic function assessed were 24 hour blood pressure measurements, metabolic syndrome markers, neuroendocrine markers [cortisol and 3-methoxy-4-hydroxy-phenylglycol (MHPG)], inflammatory and haemostatic variables (fibrinogen, C-reactive protein, plasminogen activator inhibitor-1 and D-dimer). Manuscript 1, focused on LVH as a marker of cardiovascular dysfunction and metabolic syndrome components as markers of cardiometabolic function. The aim of the study was to assess the associations between LVH and metabolic syndrome (MetS) risk markers in participants with and without depressive symptoms. Results revealed that in African men with depressive symptoms the most significant determinants of LVH were systolic blood pressure (SBP) and the percentage glycosylated haemoglobin (HbA1c). While in African women (with depressive symptoms), this association was determined by low high-density lipoprotein (HDL-cholesterol). The study concluded that in black African men, independent of depressive symptoms, cardiometabolic factors (namely SBP and HbA1c) may be the driving significant factors in the development of cardiovascular diseases. Furthermore, the data showed that depressive symptoms in African women were associated with a measure of target end organ damage, and that this association was driven by a metabolic factor. Manuscript 2, the aim of this manuscript was to examine the relationship between depressive symptoms, neuroendocrine responses [with cortisol and 3-methoxy-phenylglycol (MHPG) as markers] and cardiovascular risk, i.e. LVH. The results revealed that Africans with depressive symptoms demonstrated blunted cortisol and MHPG levels in response to acute mental stress, in comparison to those without symptoms of depression. Additionally, these low cortisol and blunted MHPG responses were associated with LVH in this ethnic group. The conclusion for this manuscript was that, blunted neuroendocrine responses linked depressive symptoms and ECG left ventricular hypertrophy in Africans. When coupled to their hypertensive status, these vasoconstrictive responses (cortisol and MHPG) may underpin the increased long-term depression and vascular disease risk in urban Africans. Manuscript 3, the aim of this manuscript was to investigate the relationship between depressive symptoms and inflammatory/haemostatic markers in a cohort of urban-dwelling black African men and women. Our data demonstrated hypercoagulation vulnerability in African men with depressive symptoms. The African men with signs of depression displayed higher plasminogen activator inhibitor (PAI-1) levels and marginally elevated D-dimer levels. It was concluded that hypercoagulation may partially be the mediating factor between depressive symptoms and cardiovascular risk in African men; a situation that may be exacerbated by hyperkinetic blood pressure. In conclusion, through the assessement of cardiometabolic function and neuroendocrine responses, it seems that Africans withdepressive symptoms are at great risk for cardiovascular related morbidity and mortality, this was particulary evident in the African men (Manuscript 1 and 3). Additionally, it appears that blunted neuroendocrine responses and hypercoagulation could be seen as possible cardiovascular risk markers in Africans with depressive symptoms. / PhD (Physiology), North-West University, Potchefstroom Campus, 2014