published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / abstract / Paediatrics and Adolescent Medicine / Doctoral / Doctor of Philosophy

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

Ischaemic heart disease is the most common cause of mortality in the western hemisphere and it is rapidly becoming the leading cause of death globally. Moreover, therapeutic interventions by cardiologists and cardiac surgeons frequently subject the heart to acute I/R injury, which in itself can cause mortality. Recent investigations of adult stem cells have primarily focused on their regenerative potential for chronic ischaemic heart disease. In this thesis, I have investigated the hypothesis that adult bone marrow derived stem cells are cardioprotective in acute regional myocardial I/R injury. In a rat model of left anterior descending coronary artery (LAD) reversible occlusion and reperfusion, I demonstrate that an intravenous bolus of adult bone marrow derived (1) bone marrow mononuclear (BMNNC) and (2) mesenchymal stem cells (MSC) upon reperfusion can attenuate infarct size. This effect is comparable to ischaemic preconditioning (IPC), which is the gold standard for cardioprotection. Next, I demonstrated the mechanisms for adult stem cell cardioprotection are principally anti-apoptotic and depend upon stem cell secreted factors to (1) activate phosphatidylinositide 3-kinase (PI3)/Akt cell survival kinase-signaling pathway (2) inhibit glycogen synthase kinase-3β (3) inhibit p38MAPK (4) inhibit nuclear translocation of p65NF-κB. 7 Proteomic analysis of myocardium subjected to I/R and treated with either BMMNC or BMMNC derived supernatant (BMS) upon reperfusion demonstrated higher expression of a whole host of pro-survival proteins. These were notably (1) 14-3-3-ε protein (2) anti-oxidant peroxiredoxin-6 (3) heat shock protein (HSP) αB-crystallin, HSP72, HSP tumour necrosis factor receptor-1 associated protein, and HSP ischaemia responsive protein-94 (4) glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (5) mitochondrial aconitase and mitochondrial voltage-dependent anionselective channel protein-1. Thereafter, I investigated the mobilization of endogenous bone marrow stem cells and trafficking to the ischaemic myocardium by stromal cell derived factor-1 (SDF-1) /chemokine, receptor type 4 (CXCR4) signaling. I demonstrate high up-regulated expression of CXCR4 and CD26 in BMMNC following IPC, which might have a role in IPC-mediated cardioprotection. Finally, and in concordance with this finding I demonstrate that both IPC and an exogenous MSC bolus upon reperfusion can synergize to abolish acute myocardial I/R injury.

Ingestion of vegetables rich in inorganic nitrate (NO3-) content has emerged as an effective method, via the formation of a nitrite (NO2-) intermediate, for acutely elevating vascular nitric oxide (NO) levels. As such a number of beneficial effects of NO3- ingestion have been demonstrated including the suggestion that platelet reactivity is reduced. I initially investigated whether inorganic NO3- supplementation might also reduce platelet reactivity in healthy volunteers and have determined the mechanisms involved in the effects seen. I conducted a randomised crossover study in 24 (12 of each sex) healthy subjects assessing the acute effects of potassium nitrate capsules (KNO3, 8 mmol) vs placebo (KCl) control capsule ingestion on platelet reactivity. Inorganic NO3- ingested via supplementation raised circulating NO3- and NO2- levels in both sexes and attenuated ex vivo platelet aggregation responses to adenosine diphosphate (ADP) and, albeit to a lesser extent, collagen but not epinephrine in male but not female volunteers. These inhibitory effects were associated with a reduced platelet P-selectin expression and elevated platelet cyclic guanosine monophosphate (cGMP) levels. In addition, I have shown that NO2- reduction to NO occurs at the level of the erythrocyte and not the platelet. These results demonstrate that inorganic NO3- ingestion, whether via the diet or through supplementation, results in a modest decrease in platelet reactivity in healthy males. I then sought to examine the effects of 6 weeks daily intake of NO3--rich beetroot juice versus a placebo NO3--deplete juice on endothelial and platelet function in a cohort of otherwise healthy non-diabetic untreated hypercholesterolaemics. In this randomised double blind placebo controlled parallel study 69 subjects were recruited. The primary end point was change in endothelial function determined using ultrasound flow-mediated dilatation (FMD). Secondary endpoints included change in pulse wave analysis (PWA), aortic pulse wave velocity (aPWV), platelet P-selectin and platelet monocyte aggregate (PMA) expression and plasma, urine and salivary NO3- and NO2- levels. Baseline characteristics, including lipid levels, were similar between the groups. Dietary NO3- caused an improvement in FMD of ~24% from 4.6%±2.2% to 5.7%±2.6% in the treatment group (p<0.001) not seen in the placebo group (4.5%±1.9% versus 4.3%±1.8% p=0.07). This improvement in FMD was also noted following acute administration of dietary NO3-. Small but significant improvements also occurred in aPWV and PWA augmentation index (p=0.04). The % of platelet monocyte aggregates was significantly reduced in the NO3- limb by 7.6% versus an increase of 10.1% in the placebo group (p=0.004). No adverse effects of dietary NO3- were detected. In this study population, chronic dietary NO3- ingestion improves endothelial function, vascular stiffness and platelet markers of atherogenesis in a cohort of hypercholesterolaemics who are otherwise at increased risk of cardiovascular disease (CVD). This thesis provides strong support for assessment of the potential of dietary NO3- as a primary prevention strategy to prevent atherothrombotic and atherogenic complications in larger cohorts.

The purpose of this project was to develop a practice guideline for screening patients at risk for cardiovascular disease, educate the staff at the site about the guideline, and implement the guideline at a primary care clinic. The intention was to identify and treat patients at risk for cardiovascular disease to prevent occurrence of heart disease. Cardiovascular disease includes hypertension, coronary heart disease, heart failure, and stroke. Coronary heart disease is one of the leading causes of death in the Western world. The local practice problem and focus of this project was underprescribed statin therapy for patients at risk for developing heart disease at a clinic in the southern United States. The practice-focused question that guided this project explored whether an evidence-based clinical guideline that might impact the prescription of statins for the prevention of cardiovascular disease would be approved for implementation in a primary care clinic serving adult and geriatric patients. The appraisal of guidelines for research and evaluation and the Fineout-Overholt model were used to guide this project. Sources of evidence to meet the purpose of this project were obtained from the literature and scholarly articles. The results of the presentation to the expert panel indicated that this clinical practice guideline would be implemented at the project site and would be used by nurse practitioners and physicians. The implications of this project for positive social change might include improved management of patients who are at risk for heart disease and a decrease in premature deaths related to cardiovascular disease.

Thesis (MPH) --University of Limpopo, 2007. / Aim of the study: To determine knowledge of CPR and heart attack or cardiac arrest signs and symptoms among university students. Study Design: A questionnaire based descriptive, cross – sectional study. Setting: University of Limpopo – Turfloop Campus in Limpopo Province of South Africa. Subjects: A total sample of 400 students participated in the study. The sample was selected randomly using simple random sampling techniques. Outcome measures: The faculty, age, gender and level of study were determined as well as the knowledge each student has on signs and symptoms of impending heart attack and CPR.Results: Of the 400 students only 26% (n=104) knew the signs and symptoms of an impending heart attack as well as out of hospital management of heart attack by performing CPR. There were differences between and within faculties, age groups, gender and level of study. Based on the Bonferroni test the student from faculty of Sciences, Health and Agriculture are more likely (p-value 0017) to know when to perform CPR compared to students from other faculties. Level of study is not associated (p-value 0128) with how much the students know about the timing and indications of CPR. Overall female students performed worse with 79% (n=123) responding incorrectly to the questions compared to 69% (n=169) males. Conclusion: Based on the results of this study it safely can be concluded that the students’ knowledge of signs and symptoms of an impending heart attack and CPR procedure is poor. It is therefore important for the university as a center of teaching and learning to consider including as part of university curriculum, basic life support and first aid courses which include CPR. The inclusion of basic life support and first aid in university curriculum will prepare students to be able to effectively manage out of hospital heart attack and reduce mortality resulting from the latter. The findings of this study might to a certain extent be reflecting what the public’s knowledge on the subject is, hence the need for the policy makers to take serious note of the findings when public health promotion programmes are developed.

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.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). The understanding of the genetics and inheritance of TOF is limited. Although about 15% of cases are associated with a 22q11.2 deletion, the majority have no known aetiology. Even in 22q11.2 Deletion Syndrome (22q11DS), factors that increase the likelihood of CHD expression are poorly understood. We aimed to determine the prevalence and phenotypes of CHD in relatives of adults with TOF. We also investigated the prevalence of CHD in relatives without a 22q11.2 deletion of individuals with 22q11DS. Offspring of patients with TOF had the greatest prevalence of CHD. Diverse cardiac phenotypes, including left heart obstructive lesions, were found in families. We also found that unaffected relatives of individuals with 22q11DS had a greater prevalence of complex CHD over population expectations, suggesting that modifier genetic factors may be involved in expression of CHD in 22q11DS.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). The understanding of the genetics and inheritance of TOF is limited. Although about 15% of cases are associated with a 22q11.2 deletion, the majority have no known aetiology. Even in 22q11.2 Deletion Syndrome (22q11DS), factors that increase the likelihood of CHD expression are poorly understood. We aimed to determine the prevalence and phenotypes of CHD in relatives of adults with TOF. We also investigated the prevalence of CHD in relatives without a 22q11.2 deletion of individuals with 22q11DS. Offspring of patients with TOF had the greatest prevalence of CHD. Diverse cardiac phenotypes, including left heart obstructive lesions, were found in families. We also found that unaffected relatives of individuals with 22q11DS had a greater prevalence of complex CHD over population expectations, suggesting that modifier genetic factors may be involved in expression of CHD in 22q11DS.