University of Macau / Faculty of Social Sciences. / Department of Communication

Background: Premenopausal black women have a 2-3 fold greater rate of coronary heart disease (CHD) than premenopausal white women. The purpose of this study was to provide insight into the reasons for this difference. Methods and Results: We compared CHD risk factors in 100 black and 100 white, healthy premenopausal women age 18-45 years and of relatively advantaged socioeconomic status. Black women consumed diets higher in saturated fat and cholesterol (12% of kcal as saturated fat and 360 mg of cholesterol per day) than did white women (10% of kcal and 290 mg/day) (p=0.008). Black women also had a higher body mass index (BMI) (32.0±9.2 vs. 29.0±9.4 kg/m², p=0.021), and higher systolic (124±17 vs. 115±14 mmHg, p<0.0001), and diastolic (79±14 vs. 75±11 mmHg, p=0.048) blood pressures. The mean plasma Lp(a) concentration was higher in the black women (40.2±31.3 mg/dl) than in the white women (19.2±23.7 mg/dl)(p<0.0001). The black women, however, had lower plasma triglyceride levels (0.91±0.46 vs. 1.22±0.60 mmol/L, p<0.0001), and a trend toward higher HDL cholesterol levels (1.37±0.34 vs. 1.29±0.31 mmol/L, p=0.064) than the white women. Plasma total and LDL cholesterol levels were similar. Rates of cigarette smoking and alcohol intake were low and similar between the races. Black women additionally had higher levels of plasma total homocysteine (8.80 vs. 7.81 μmol/L, p=0.013), lower plasma folates (3.52 vs. 5.23 ng/ml, p<0.0001), and higher vitamin B₁₂ levels (522 vs. 417 pg/ml, p<0.0001) than white women. More white women than black women took a multivitamin supplement (42.4% vs. 24.7%, p=0.019). When adjusted for multivitamin use, homocysteine levels did not differ, but plasma folate remained significantly lower in black women. Sixty-eight percent of black women carried the wild-type methylenetetrahydrofolate reductase genotype, 32.0% were heterozygotes, and none were homozygotes. Of the white women, 47.4% were wild-type, 40.3% heterozygotes, and 12.3% homozygotes (p=0.013). Conclusions: Premenopausal black women consumed more saturated fat and cholesterol and had a higher mean body mass index, blood pressure, Lp(a), and plasma total homocysteine levels than white women. These differences in coronary risk factors may explain the higher incidence of CHD in premenopausal black compared to white women. / Graduation date: 1998

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, 2017. / Background: In spite of the contributions of cardiovascular disease (CVD) to morbidity and mortality in chronic kidney disease (CKD) worldwide, there are no studies that have looked at cardiovascular risk factors (CVRFs) and their association with cardiovascular changes in African children with CKD. Several CVRFs have been implicated in the initiation and progression of cardiovascular changes in children with CKD, and these changes have been reported even in early CKD. This study investigated CVRFs and their association with cardiovascular changes in South African children with CKD. Method: This comparative cross sectional study recruited children (5-18 years) with CKD being followed up at the Division of Paediatric Nephrology of the Charlotte Maxeke Johannesburg Hospital and the Chris Hani Baragwanath Academic Hospital. One hundred and six children with a spectrum of CKD including those on chronic dialysis (34 CKD I, 36 CKD II-IV and 36 CKD V-dialysis) were enrolled over a 12 month study period. All patients had a short history taken along with a physical examination. Blood samples for serum creatinine, urea, albumin, calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphatase, total cholesterol, haemoglobin and C-reactive protein, Vitamin D, Fibroblast growth factor-23 (FGF-23), Fetuin-A and genomic DNA studies were taken. Where feasible, transthoracic echocardiography and high resolution ultrasonography of the common carotid artery was performed. Results: The overall median age of the patients was 11 years (8-14 years), with a male female ratio of 2.1:1. Several CVRFs detected include hypertension, proteinuria, anaemia, hypercholesterolaemia and dysregulated mineral bone metabolism. The most common CVRF detected was anaemia (39.6%) and its prevalence was highest in the dialysis group when compared with the other CKD groups. The overall median (range) cIMT was 0.505mm (0.380-0.675), and was highest in patients with dialysis dependant CKD (p=0.003). The distribution of left atrial diameter (LAD) and left ventricular mass (LVM) differed significantly (p<0.05) across the different CKD groups. Abnormal LAD was seen in 10% of patients; left ventricular hypertrophy (LVH) in 27%; left ventricular systolic dysfunction in 6% and diastolic dysfunction in one patient. Mean arterial pressure and haemoglobin levels were independently associated with cIMT; hypertension was independently associated with concentric LVH; and age and hypoalbuminaemia were independently associated with eccentric LVH. Overall, the dialysis group had the highest prevalence of vascular changes, cardiac changes and associated risk factors. A skewed pattern of Fetuin-A and FGF-23 levels with medians (range) of 57.7 (0.9-225.2) mg/dL and 28.9 (0-3893.0) pg/ml respectively, were observed. The levels of these two biomarkers varied significantly between the different CKD groups (p<0.05). Fetuin-A was independently associated with abnormal LAD but no similar relationship with other cardiovascular changes and plasma levels of Fetuin-A and FGF-23 was found. Plasma FGF-23 levels correlated better with markers of bone mineralization than Fetuin-A. Eight Fetuin-A SNPs were analysed; rs2248690, rs6787344, rs4831, rs4917, rs4918, rs2070633, rs2070634 and rs2070635. We found an association between log-transformed Fetuin-A levels and the SNP rs4918 G-allele compared to the rs4918 C-allele (p=0.046) and the rs2070633 T-allele when compared to the rs2070633 C-allele (p=0.015). Markers of MBD such as phosphate and PTH levels were associated with Fetuin-A SNPs. The rs6787344 G-allele was significantly associated with phosphate levels (0.042), and the rs4918 G-allele with PTH (p=0.044). Seven deaths were recorded in the dialysis group during the study period and severe hypertension and intracranial bleed were the most common causes of death. Modifiable risk factors such as increased total cholesterol (TC) and decreased albumin levels were more commonly seen among the deceased dialysis patients. Conclusion: A high prevalence of CVRFs and cardiovascular changes were observed in the study groups, even in those with mild to moderate disease. Information obtained from the study highlights the need to address modifiable CVRFs such as hypertension, anaemia and hypoalbuminaemia in children with CKD and also the need to determine new, population specific, paediatric reference values for cIMT in healthy African children. Finally, the study was able to demonstrate differences in the relationship between Fetuin A SNPs and Fetuin-A levels and cardiovascular changes in our study population when compared with previously published data. We postulate that these differences may be due to genetic differences between our population and other population groups previously studied. / LG2018

Prediction for future coronary artery disease (CAD) from high-density lipoprotein (HDL) and triglyceride (TG) measurements are based off of a single measurement that has been shown to be variable. To better determine risk for CAD based on blood lipids, studies in the postprandial state are warranted. To assess the reproducibility of TG clearance, 10 men underwent three trials of a 70g oral fat loading test with blood samples collected every two hours for eight hours. These trials were all scheduled at least one week apart. Men who had fasting TG concentrations > 250 mg - dL -' were excluded from the study. Each subject presented to the laboratory having abstained from exercise for 24 hours and alcohol 72 hours prior to the upcoming trial. Each subject was also provided with a standardized frozen dinner to eat the night before at a time which allowed the subject to be 12 hours fasted for the next days' trial. To specifically assess postprandial lipemia, TG concentrations were plotted against bi-hourly collection times to form a curve. The area under this curve was then calculated to determine PPL area. Itwas found that there was no significant difference in area under the TG curve (p = 0.25) for any of the three trials (1096 ± 168, 948 ± 105, and 995 ± 127 mg - dL -' - 8 • hr-' respectively for trials one, two, and three). Pearson correlations between trials were 0.79 for trials one and two, 0.82 for trials two and three, and 0.90 for trials one and three. Also, there was no significant difference in peak TG (p = 0.34) on each of the three trial days (167 ± 27, 150 ± 16, and 151 ± 19 mg • dL -1 in peak TG for trials one, two, and three respectively). Time taken to reach peak TG concentrations (p = 0.20) or time to return to baseline TG (p = 0.27) were not significantly different across three trial days. The men in this study reached peak TG concentrations in this study in 3.2 ± 0.5, 4.0 ± 0.4, 4.0 ± 0.3 hours respectively for trials one, two, and three. Time to return to baseline was 6.8 ± 0.6, 7.4 ± 0.4, 7.8 ± 0.4 hours for trials one through three respectively. Correlations between trials and the lack of a difference between trials using repeated measures ANOVA in regards to PPL area gives some preliminary evidence that some postprandial measures such as PPL area and can be reproduced across trials. However, the intra-individual variation was 19 ± 4% which provides no additional support for reproducibility of PPL. Additionally, results from this study, as well as all others pertaining to the study of reproducibility of PPL are specific to the protocol used and the method of interpretation. / School of Physical Education

Coronary heart disease (CHD) claims millions of lives every year worldwide. In the developed countries, a clear connection has been documented between a decline in CHD mortality and modifiable risk factor reductions. While raising awareness of CHD risk factors reduction is imperative, no valid instrument backed by robust psychometric data is available to measure people‘s awareness in this regard. In addition, especially among the Chinese population, despite many studies already conducted concerning awareness of CHD-related issues, inconsistency in how people define and measure this concept remains. This study aimed to develop a valid instrument that measures Hong Kong Chinese people‘s awareness of CHD risk factors reduction. The study involved two phases. Phase I involved qualitative data collection through 18 focus group interviews (n=100). Participants in this phase included members from three groups: (1) the low risk general public, (2) people having multiple CHD risk factors either with or without CHD, and (3) people who have been diagnosed of myocardial infarction. The objective of this phase was to identify key elements and to clarify the concept inherent in awareness, from which served as a basis to generate items to form the awareness instrument. Upon completion of this phase, three main categories were generated including: CHD knowledge, perceptions of CHD, and risk control efficacy. Under these main categories, twelve subcategories emerged. Under the category of CHD knowledge, the subcategories were: pathological causes of CHD, external forces in causing CHD, modifiable and non-modifiable risk factors, CHD trends, symptoms of CHD, and knowledge of CHD prevention. Under the category of perceptions of CHD, the subcategories were: perceived seriousness of CHD and perceived risk. Under the category of risk control efficacy, the subcategories were: planning of health actions, control over risk reducing behaviour, perceived opportunities to understand CHD, and chest pain appraisal/perceptions. A total of 70 items were generated to form the Awareness of Coronary heart disease Risk Factors Reduction (ACRFR) scale. The second phase of this study focused on the evaluation of the psychometric properties of ACRFR scale. The objective of this phase was to establish the validity and reliability of the instrument. It commenced with determining the content validity by expert review, followed by identifying the factor structure, construct validity and reliability. A good content validity index (CVI) of 0.84 was achieved. The factor structure of ACRFR was identified through exploratory factor analysis (EFA) data collected from a sample (n=232) of the three groups as described in phase one. The final results revealed a seven-factor model with 43 items accounting 49.5% of the total explained variance. The seven factors were: (1) CHD knowledge, (2) planning of health actions, (3) perceived ability to monitor health-related behaviour, (4) perception of risk, (5) perceived opportunities to understand CHD, (6) perceived seriousness of CHD, and (7) chest pain appraisal/perceptions. The factor structure of ACRFR was further cross-validated by confirmatory factor analysis (CFA) in another independent sample (n=225) of the three groups. Goodness of fit statistics fell within acceptable ranges: 2 / d = 1.6, RMSEA = 0.053, NNFI = 0.92, IFI = 0.93, CFI = 0.93. The factor model was further supported by hypothesis testing and known-groups comparisons. The results of hypothesis testing demonstrated significant correlations between ACRFR and other measures. Known-groups comparisons among subjects with MI, those with CHD and without CHD provided satisfactory evidence for construct validity. Reliability of this developed instrument, as estimated by the internal consistency Cronbach‘s alphas, ranged from 0.60 to 0.90 for each sub-scale and for the total scale was 0.82, and the test-retest reliability was 0.89, suggesting good instrument reliability. While current literature reveals no objectively devised conceptual definition of ACRFR and that no published instrument was made available for healthcare professions to enhance people‘s awareness of reducing CHD, this study fills these gaps. It is envisaged that this developed instrument could assist healthcare professional in accurately estimating people‘s awareness of risk factors reduction that could provide valid and reliable data that could inform future directions in CHD prevention and cardiac health promotion.

The global burden of heart disease increases every year. It has been estimated that by the year 2020, coronary artery disease (CAD) will be the number one cause of death worldwide. Indian populations throughout the world have the highest prevalence of CAD and early onset of the disease compared to other ethnic groups. Glutathione S-transferases (GSTs) detoxify environmental agents which influence the onset and progression of disease. Dysfunctional detoxification enzymes are responsible for prolonged exposure to reactive molecules and can contribute to endothelial damage, an underlying factor in CAD. Uncoupling proteins (UCPs) 2 and 3 play an important role in the regulation of oxidative stress which contributes to chronic inflammation. Coronary artery disease is a chronic inflammatory disorder characterized by elevated levels of C-reactive protein (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). Polymorphisms of these genes have been linked to CAD and other chronic diseases. Statins, metabolised in the liver, are the most commonly used drug to control atherosclerosis progression in CAD patients. The pleiotropic effects of statins have been attributed to both favourable and adverse outcomes in CAD patients particularly related to myopathy and hepatotoxicity. All patients (n=102) recruited into this study were South African Indian males. A corresponding age-, gender- and ethnicity-matched control group (n=100) was also recruited. The frequency of the GSTM1 +/0, GSTP1 A105/G105, IL6 -174G/C and CRP -390C/A/T genotypes was assessed by polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). For the in vitro study, the biological effect of atorvastatin on HepG2 cells was assessed. The metabolic activity, cytotoxicity, oxidative stress and nitric oxide production was assessed by the ATP, lactate dehydrogenase (LDH), thiobarbituric acid reactive substance (TBARS) and Griess assays, respectively. The profile of 84 microRNA (miRNA) species was evaluated using the miRNA Pathway Finder PCR SuperArray. The predicted targets of up-regulated miRNAs were determined using the online software, Targetscan. The mRNA levels of guanidinoacetoacetate (GAMT), arginine glycine aminotransferase (AGAT) and spermine oxidase (SMO) were determined using quantitative PCR. Western blotting was used to determine GAMT and phosphorylated p53 levels in treated cells. The GSTM1 0/0 and GSTP1 A105/A105 genotypes occurred at higher frequencies in CAD patients compared with the control group (36% vs. 18% and 65% vs. 48%, respectively). A significant association with CAD was observed in GSTM1 0/0 (odds ratio (OR)=2.593; 95% confidence interval (CI) 1.353 - 4.971; p=0.0043) and GSTP1 A105/A105 OR=0.6011; 95% CI 0.3803 - 0.9503; p=0.0377). We found a significant association between smoking and CAD; the presence of either of the respective genotypes together with smoking increased the CAD risk (GSTP1 A105 relative risk (RR)=1.382; 95% CI 0.958 - 1.994; p=0.0987 and GSTM1 null RR=1.725; 95% CI 1.044 - 2.851; p=0.0221). The UCP2 -866G/A and UCP3 -55C/C genotypes occurred at highest frequency in CAD patients (59% vs. 52% and 66% vs. controls: 63% respectively) and did not influence the risk of CAD. Homozygous UCP3 -55T/T genotype was associated with highest fasting glucose (11.87±3.7mmol/L vs. C/C:6.11±0.27mmol/L and C/T:6.48±0.57mmol/L, p=0.0025), HbA1c (10.05±2.57% vs. C/C:6.44±0.21% and C/T:6.76±0.35%, p=0.0006) and triglycerides (6.47±1.7mmol/Lvs. C/C:2.33±0.17mmol/L and C/T:2.06±0.25mmol/L, p<0.0001) in CAD patients. A significant association between the G allele of the IL6 -174 polymorphism and non-diabetic CAD patients was found (p=0.0431 odds ratio: 1.307, 95% CI: 1.047-1.632). A significant association with the C allele of the -390 CRP triallelic variants and CAD (p=0.021 odds ratio: 1.75, 95% CI: 1.109-2.778) was also found using a contingency of the C allele vs. the minor A and T allele frequencies. The strength of the association of the C allele with non- diabetic CAD subjects was much higher (p=0.0048 odds ratio: 2.634, 95% CI: 1.350-5.138). Circulating median levels of IL-6 (0.9 (0.90, 0.91) pg/ml and 0.9 (0.87, 0.92) pg/ml) and CRP (5.65 (1.9, 8.2) mg/l and 2.90 (1.93, 8.35) mg/l) were similar between CAD patients and controls, respectively. A similar finding was observed between controls and non-diabetic CAD subjects. Levels of IL-6 and CRP in CAD subjects were not significantly influenced by polymorphic variants of IL-6 and CRP. In the control group, the level of IL-6 was significantly influenced by the IL6 -174 G allele (p=0.0002) and the CRP -390 C allele (p=0.0416), where subjects with the homozygous GG (0.9 (0.9, 1,78) pg/ml) and CC (0.9 (0.9, 0.95) pg/ml) genotype had higher levels than the C allele carriers (0.9 (0.64, 0.91) pg/ml) or A and T carriers (0.9 (0.69, 0.91) pg/ml) combined. The lowest measure of proliferation/metabolism in HepG2 cells was observed at 20μM atorvastatin, with 82±9.8% viability. The level of cytotoxicity was increased in statin treated cells from 0.95±0.02 units to 1.11±0.03 units (p=0.001) and malondialdehyde levels was reduced from 0.133±0.003 units to 0.126±0.005 units (p=0.009) whilst nitrite levels were elevated (0.0312±0.003 units vs. control: 0.027±0.001 units, p=0.044). MicroRNAs most significantly upregulated by atorvastatin included miR-302a-3p (3.05-fold), miR-302c-3p (3.61-fold), miR-124-3p (3.90-fold) and miR-222-3p (4.4-fold); miR-19a-3p, miR-101-3p and let-7g were downregulated (3.63-fold, 2.92-fold, 2.81-fold, respectively). A list of miRNA targets identified included those with a role in metabolism and inflammation. The miR-124a specifically targets the mRNA of GAMT and SMO. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2012.

The emphasis of the study was to determine the degree of correlation between the Conicity Index and known risk factors for heart disease. Conicity Index was shown in one study to be a useful screening tool in assessing the relationship between body composition and risk for heart disease. This study was designed to provide nutrition education and teach lifestyle modification to fourteen Veteran's Affairs patients. Change in specific risk factors including Waist-to-Hip Ratio, Body Mass Index, serum lipid levels and dietary intakes were correlated with change in Conicity Index over the six month study. Results from the present study did not suggest that the Conicity Index would serve as an effective screening tool for the present population. Mean body weight, body mass index, hip circumference, cholesterol and triglyceride levels, total caloric and fat intake all decreased significantly as a result of the program. Through nutrition education, behavior modification and group support, the risk for heart disease was successfully modified in this population. / Department of Family and Consumer Sciences

This study examined percent fat, fat distribution, and resting cortisol concentrations between personality types for coronary artery disease (CAD) risk. Males (n= 29, 43 ± 8.8 years) selected through the Jenkins Activity Survey, scoring >_ 75th percentile (Type A=15) or S 30th percentile (Type B=14), had the following measures: percent fat, lipid profile, and waist-to-hip ratio. Each hour, heart rate, blood pressure (SBP, DBP), and cortisol were measured. A prediction model determined risk of CAD. Type A had a tendency to have higher DBP, but was only significant at one time point (F= 3.390, p= .022). Type B showed significantly higher total (t= -2.688, p= .012) and LDL cholesterol (t= -3.612, p= .001). Although we did not show many significant differences between groups, within groups, many significant correlations were detected among the variables measured. Further studies will justify the associations between percent fat, fat distribution, and cortisol across personality types. / School of Physical Education

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / School of Physical Education, Sport, and Exercise Science

Background Sedentary behaviour has incrementally increased over the past few years. The scientific community recognises this behaviour as a twenty first century disease which reflects the detrimental effects of excessive sitting on several adverse functional and clinical health outcomes, such as chronic disease, in the general adult population. Many evolving contemporary occupations require that employees sit an average of eight hours per day at work stations or office desks, especially when using communication technology. Even after accounting for the self-reported time spent in recommended physical activity, the negative dose-response relationship between time spent in sedentary behaviour and the all-cause and cardiovascular disease mortality still remain. Aim: To establish a profile of sedentary behaviour as well as levels of physical activity and coronary artery disease risk factors in employees at a tertiary institute in the Eastern Cape Province of South Africa. Another aim is to determine whether an association exists between the aforementioned variables.