Background: Cardiovascular disease (CVD) is becoming one of the leading causes of death in middle and low income countries, with ischaemic heart disease specifically being predicted to be the 4th and 5th causes respectively. The numerous risk factors for the development of CVD have been extensively researched; however, the same wealth of data is not available for the black South African population as there is for Caucasians. Although the same risk factors that are present in Caucasians have been seen to be present in the black South Africans, there are questions regarding the contributory roles of the individual risk factors, particularly within the context of urbanisation. The role of diet in CVD has been widely studied and it is known that with urbanisation there are dietary changes which are thought to add the development of CVD. With urbanisation, however, there are numerous other lifestyle changes taking place within a population, making it difficult to isolate and make conclusions of the individual role of diet. Added to this is the complex issue of assessing dietary intake. Assessing only nutrient or food intake does not give a holistic picture of dietary habits. The main aim of this study was to determine the association between dietary intake and CVD risk in black South Africans in the context of urbanisation. Methods: The first study that forms part of this thesis was a case-control study aimed at exploring the risk factor profile and clinical presentation of black South African patients with coronary artery disease (CAD). In this study clinical, biochemical and nutrient intakes were compared with a black South African control group that were matched for age and body composition. The second study to form part of this thesis aimed to relate the dietary intakes of the Prospective Urban and Rural Epidemiological (PURE) study population to CVD risk associated with urbanisation, by using both nutrient intake and predefined diet quality scores (DQS). The Healthy Diet Indicator (HDI) and the Deficiency and Excess Score were carefully selected from the large number of available scores and adapted as best as possible for the black South African population. The third study aimed to investigate the role of dietary intake by using nutrients as well as food group consumption patterns as a risk factor in urbanised black South African CAD patients. The dietary habits of the coronary artery disease (CAD) patients were compared to that of an apparently healthy reference group of volunteers selected from the PURE study population. This urbanised reference group was from a similar socio- demographic background and was selected according to their risk for CVD. The Reynolds Risk score which includes C-reactive protein as factor was used to stratify the PURE population into CVD risk categories, in order to select the reference group, which had a low risk (<5%) of developing CVD within the next 10 years. Dietary intake was assessed by comparing nutrient and food group intake (including the ultra-processed food group category). Results and discussion: Black South African CAD patients had increased levels of the same risk factors that are seen in Caucasians with insulin resistance and LDL size being particularly significant in their contribution. Apart from a lower vitamin C intake, no differences in dietary intake and physical activity were observed between the CAD and control group. When comparing the dietary intake of the rural and urban group, the urban group, who had an increased CVD risk, had higher intakes of macro- and micronutrients as well as higher DQS. The DQS must however be interpreted with caution, as when looking at the absolute intakes of individual components of the scores, the urban group was still deficient in a numerous vital micronutrients. A similar picture was seen in the third study, in that the CAD patients also consumed more saturated fatty acids and ultra-processed foods than the reference group, as well as more of the “protective” foods such as fruit and vegetables. However, although their dietary habits could be considered prudent, they were still inadequate in numerous important micronutrients. Conclusion and recommendation: This thesis therefore shows that there are two sides of the story regarding the role of diet in CVD in black South Africans. Although it is important to follow prudent dietary guidelines so as to control the intake of nutrients and foods known to play a role in the development of CVD, it is just as important to ensure adequate intake of the foods rich in micronutrients known to protect against CVD. Dietary advice and prevention programs should also focus on the adequacy aspect of the diet, such as increasing fruit and vegetable and low fat dairy intake, not only on the prudent diet aspect. Additionally, nutrient intake alone does not adequately explain the link between diet and CVD and additional analyses such food consumption patterns are required. / Thesis (PhD (Dietetics))--North-West University, Potchefstroom Campus, 2013

Background: Cardiovascular disease (CVD) is becoming one of the leading causes of death in middle and low income countries, with ischaemic heart disease specifically being predicted to be the 4th and 5th causes respectively. The numerous risk factors for the development of CVD have been extensively researched; however, the same wealth of data is not available for the black South African population as there is for Caucasians. Although the same risk factors that are present in Caucasians have been seen to be present in the black South Africans, there are questions regarding the contributory roles of the individual risk factors, particularly within the context of urbanisation. The role of diet in CVD has been widely studied and it is known that with urbanisation there are dietary changes which are thought to add the development of CVD. With urbanisation, however, there are numerous other lifestyle changes taking place within a population, making it difficult to isolate and make conclusions of the individual role of diet. Added to this is the complex issue of assessing dietary intake. Assessing only nutrient or food intake does not give a holistic picture of dietary habits. The main aim of this study was to determine the association between dietary intake and CVD risk in black South Africans in the context of urbanisation. Methods: The first study that forms part of this thesis was a case-control study aimed at exploring the risk factor profile and clinical presentation of black South African patients with coronary artery disease (CAD). In this study clinical, biochemical and nutrient intakes were compared with a black South African control group that were matched for age and body composition. The second study to form part of this thesis aimed to relate the dietary intakes of the Prospective Urban and Rural Epidemiological (PURE) study population to CVD risk associated with urbanisation, by using both nutrient intake and predefined diet quality scores (DQS). The Healthy Diet Indicator (HDI) and the Deficiency and Excess Score were carefully selected from the large number of available scores and adapted as best as possible for the black South African population. The third study aimed to investigate the role of dietary intake by using nutrients as well as food group consumption patterns as a risk factor in urbanised black South African CAD patients. The dietary habits of the coronary artery disease (CAD) patients were compared to that of an apparently healthy reference group of volunteers selected from the PURE study population. This urbanised reference group was from a similar socio- demographic background and was selected according to their risk for CVD. The Reynolds Risk score which includes C-reactive protein as factor was used to stratify the PURE population into CVD risk categories, in order to select the reference group, which had a low risk (<5%) of developing CVD within the next 10 years. Dietary intake was assessed by comparing nutrient and food group intake (including the ultra-processed food group category). Results and discussion: Black South African CAD patients had increased levels of the same risk factors that are seen in Caucasians with insulin resistance and LDL size being particularly significant in their contribution. Apart from a lower vitamin C intake, no differences in dietary intake and physical activity were observed between the CAD and control group. When comparing the dietary intake of the rural and urban group, the urban group, who had an increased CVD risk, had higher intakes of macro- and micronutrients as well as higher DQS. The DQS must however be interpreted with caution, as when looking at the absolute intakes of individual components of the scores, the urban group was still deficient in a numerous vital micronutrients. A similar picture was seen in the third study, in that the CAD patients also consumed more saturated fatty acids and ultra-processed foods than the reference group, as well as more of the “protective” foods such as fruit and vegetables. However, although their dietary habits could be considered prudent, they were still inadequate in numerous important micronutrients. Conclusion and recommendation: This thesis therefore shows that there are two sides of the story regarding the role of diet in CVD in black South Africans. Although it is important to follow prudent dietary guidelines so as to control the intake of nutrients and foods known to play a role in the development of CVD, it is just as important to ensure adequate intake of the foods rich in micronutrients known to protect against CVD. Dietary advice and prevention programs should also focus on the adequacy aspect of the diet, such as increasing fruit and vegetable and low fat dairy intake, not only on the prudent diet aspect. Additionally, nutrient intake alone does not adequately explain the link between diet and CVD and additional analyses such food consumption patterns are required. / Thesis (PhD (Dietetics))--North-West University, Potchefstroom Campus, 2013

Systemic Lupus Erythematosus (SLE), a prototypic multi-organ autoimmune disease, is associated with a dramatically increased risk of coronary artery disease (CAD) manifesting as angina, myocardial infarction and sudden cardiac death. Traditional cardiac risk factors such as hypertension and hypercholesterolemia, measured at baseline in accordance with the Framingham model, only partially account for the increased risk of CAD in SLE. In this thesis, I have shown that blood pressure (BP), lipids and novel risk factors such as the inflammatory marker high-sensitivity C-reactive protein (hsCRP), take a dynamic course in SLE, with more than half of the variance in serial measurements over time occurring within rather than between individuals. This variability is due to changes in disease activity, treatment, accrual of other cardiac risk factors, and complications such as infection. I have demonstrated that by capturing cumulative exposure over time, ‘summary measures’ such as arithmetic mean and time-adjusted mean (AM) are better able to quantify CAD risk in patients with SLE than single-point-in-time measurements of risk factors. By incorporating ‘summary measures’ such as mean and AM into time-dependent covariate survival analysis models, I was able to quantify the magnitude of increase in CAD risk associated with increments in systolic and diastolic BP, and to demonstrate and quantify the association between several lipids / lipoproteins and CAD risk in SLE. Using this methodology, I was also able to demonstrate that despite marked variability over time, ‘summary measures’ of hsCRP are independently predictive of CAD risk among patients with SLE, highlighting the pivotal role of inflammation in atherosclerosis. Furthermore, I was able to determine lipid and hsCRP ‘cut-points’ that will aid clinicians in identifying a subgroup of patients with SLE who are at significantly increased cardiac risk.

Systemic Lupus Erythematosus (SLE), a prototypic multi-organ autoimmune disease, is associated with a dramatically increased risk of coronary artery disease (CAD) manifesting as angina, myocardial infarction and sudden cardiac death. Traditional cardiac risk factors such as hypertension and hypercholesterolemia, measured at baseline in accordance with the Framingham model, only partially account for the increased risk of CAD in SLE. In this thesis, I have shown that blood pressure (BP), lipids and novel risk factors such as the inflammatory marker high-sensitivity C-reactive protein (hsCRP), take a dynamic course in SLE, with more than half of the variance in serial measurements over time occurring within rather than between individuals. This variability is due to changes in disease activity, treatment, accrual of other cardiac risk factors, and complications such as infection. I have demonstrated that by capturing cumulative exposure over time, ‘summary measures’ such as arithmetic mean and time-adjusted mean (AM) are better able to quantify CAD risk in patients with SLE than single-point-in-time measurements of risk factors. By incorporating ‘summary measures’ such as mean and AM into time-dependent covariate survival analysis models, I was able to quantify the magnitude of increase in CAD risk associated with increments in systolic and diastolic BP, and to demonstrate and quantify the association between several lipids / lipoproteins and CAD risk in SLE. Using this methodology, I was also able to demonstrate that despite marked variability over time, ‘summary measures’ of hsCRP are independently predictive of CAD risk among patients with SLE, highlighting the pivotal role of inflammation in atherosclerosis. Furthermore, I was able to determine lipid and hsCRP ‘cut-points’ that will aid clinicians in identifying a subgroup of patients with SLE who are at significantly increased cardiac risk.

Cardiovascular disease (CVD) causes 45% of on-duty firefighter fatalities, a high fraction even when compared to the risk of CVD found in other first-responder professions like police work and emergency medical services. Monitoring and managing firefighter cardiac health is important for both individual health and public safety. In our study, we are interested in assessing the utility of the most commonly used risk assessment scoring, known as the Framingham Risk Score, in evaluating the atherosclerotic risk in asymptomatic firefighters. To this end we determined FRS for 159 male firefighters from Gwinnett County, Georgia, and compared their risk categorization against their known atherosclerotic burden as determined by CIMT and CAC. While the 20% FRS threshold, corresponding to medium risk, had a high specificity for both CAC and CIMT, it also had a low sensitivity (17% and 40%, respectively), indicating that a large percentage of individuals with clinically significant atherosclerosis are being misclassified. By adjusting the FRS threshold downward, we were able to raise the sensitivity greatly with only a modest loss of specificity. Following percutaneous transluminal coronary angioplasty for the treatment of coronary artery disease, stents are commonly implanted at the treatment site to prevent recoil and negative remodeling. To combat in-stent restenosis, an arterial healing response that results in luminal loss in stented arteries, anti-restenotic drugs like sirolimus (SES) and zotarolimus (ZES) are commonly eluted by stents to suppress cell proliferation at the treatment site. While comparative studies have revealed significant difference between bare metal stents (BMS), SES, and ZES in both clinical and histological arterial response, the molecular basis of these differences remains poorly understood. We conducted a comparative gene expression profiling study using microarrays to examine differences in gene expression and pathway function in coronary arteries exposed to ZES, SES, and BMS in a porcine animal model. These molecular profiles suggest a model of delayed restenosis, resulting from a drug-induced suppression of inflammatory responses and proliferative processes, rather than an elimination of restenosis. microRNAs play a regulatory role in metastasis-related epithelial to mesenchymal transitions and mesenchymal to epithelial transitions in ovarian cancer cells. We previously showed that over-expression of miR-429 in ovarian cancer cells drove a transition from mesenchymal phenotypes to epithelial phenotypes both in morphology and expression of markers like ZEB1, ZEB2, and E-cadherin. Our study represents the first time course analysis of miR-429-induced MET in ovarian cancer cells. We transfected Hey cells with miR-429 and assayed gene expression over the course of 144 hours at regular intervals. The cell morphology and gene expression of our transfected cells changed to become more epithelial-like at 24 and 48 hours and then became more mesenchymal-like by 144 hours. By 144 hours the average gene expression levels for 98.6% of our genes were not significantly different from the levels they started from at 0 hours when we adjusted for baseline expression changes observed in our negative control treated cells. This suggests the use of microRNAs as cancer therapies and driving cancer cells to a more drug susceptible state.

Orientador: Haroldo Wilson Moreira / Banca: Evandro José Cesarino / Banca: Luiz Carlos de Mattos / Resumo: A haptoglobina é uma glicoproteína plasmática sintetizada principalmente pelo fígado com atividade antioxidante e imunomodulatória. Sua principal função é a formação de um complexo estável com a hemoglobina livre, prevenindo a excreção de ferro pelos rins e danos causados pelo efeito oxidativo do mesmo. O polimorfismo desta proteína é caracterizado por três genótipos principais: Hp1 / Hp1, Hp2 / Hp1 e Hp2 / Hp2, sendo que estes apresentam subtipos na dependência das recombinações entre os alelos Hp1F, Hp1S, Hp2FS, Hp2SF, Hp2FF e Hp2SS. Apesar de contraditório, vários autores tentam correlacionar esses tipos e subtipos com doenças, na tentativa de responsabilizar algum deles como facilitador ou conferir resistência quanto às mesmas. Os objetivos deste estudo foram verificar as freqüências desse polimorfismo, suas freqüências alélicas e possíveis correlações em portadores e não portadores de doença arterial coronariana, bem como em doadores de sangue, pertencentes a uma parcela da população paulista. Dessa forma foram analisados 125 pacientes com DAC, 69 com ausência de DAC e 124 doadores de sangue. O material genético foi extraído, amplificado e após restrição enzimática com Dra I permitiu identificar os tipos e subtipos da haptoglobina. Os resultados permitiram concluir que essa caracterização pela técnica aplicada mostrou ser rápida e de fácil realização. Os portadores de DAC e os doadores de sangue evidenciaram maior freqüência do Hp2 / Hp2 e aqueles com ausência de DAC do genótipo heterozigoto, não sendo observada diferenças estatísticas significativas entre eles. Essa mesma observação era verificada quando estratificávamos os grupos quanto aos sexos. A freqüência alélica do Hp2 se mostrou maior que o Hp1 para os três grupos analisados. A distribuição dos subtipos da haptoglobina revelou que o prevalente...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Haptoglobin is a glycoprotein synthesized by liver with antioxidant and immunomodulatory properties. Its main function is the formation of a stable complex with free hemoglobin, preventing iron loss and damage caused by oxidative effects. The polymorphism of this protein is characterized by three main genotypes: Hp1 / Hp1, Hp2 / Hp1 e Hp2 / Hp2, and these have subtypes in dependence of the recombination among the alleles Hp1F, Hp1S, Hp2FS, Hp2SF, Hp2FF e Hp2SS. Despite contradictory, the authors try to associated types and subtypes with diseases, attempt to hold responsible for someone or to permit resistance to them. The purposes of our study were to find the frequencies of this polymorphism, their allelic frequencies and possible associations in patients with coronary artery disease and patients without coronary artery disease, as well as in blood donors, from one fraction of Brazilian population. We have analyzed 125 patients with CAD, 69 patients without CAD and 124 blood donors. Genomic DNA was extracted, amplified and after enzyme restriction with Dra I we could identify types and subtypes of haptoglobin. With the results we conclude that this applied technique is fast and it's easy to carry out. Patients with CAD and blood donors evidenced higher frequencies for Hp2 / Hp2 and patients without CAD from heterozygous genotypes, weren't observed significant statistical differences among them. The same observation was verified when we stratified the groups regarding genders. The allelic frequency of Hp2 was shown higher than Hp1 for the three groups analyzed. The distribution of haptoglobin subtypes revealed that the prevalent for all groups were represented by Hp2FS / Hp2FS, followed by Hp2FS / Hp1F in patients with CAD and without CAD and Hp2FF / Hp2FF in blood donors. The third in expression was represented by Hp1S / Hp1S in patients with CAD, Hp2FS / Hp1S in patients without...(Complete abstract click electronic access below) / Mestre

Abstract Several studies have shown that altered cardiovascular autonomic regulation is associated with hypertension, diabetes, aging, angiographic severity of coronary artery disease (CAD), and increased mortality after acute myocardial infarction (AMI). The purpose of this study was to assess the temporal changes and prognostic significance of various measures of heart rate (HR) behaviour and their possible associations to coronary risk variables, and the progression of CAD in different populations. This study comprised five patient populations. The first consisted of 305 patients with recent coronary artery bypass graft surgery (CABG) and lipid abnormalities, the second of 109 male patients with recent CABG, the third of 53 type II diabetic patients with CAD, the fourth of 600 patients with recent AMI, and the fifth of 41 elderly subjects. HR variability and non-linear measures of HR dynamics were analysed. Among the patients with prior CABG, a significant correlation existed between the baseline HR variability (standard deviation of N-N intervals, SDNN) and the progression of CAD (r = 0.26, p &lt; 0.001)). In the longitudinal study of patients with prior CABG, only the fractal indexes of HR dynamics, such as the power law slope (β) and the short-term fractal exponent (α1), decreased significantly. In diabetic patients, SDNN decreased significantly (p &lt; 0.001) during the three-year period. The reduction of SDNN was related to cholesterol, triglyceride, and glucose levels, and also to progression of CAD (r = 0.36, p &lt; 0.01). In the longitudinal follow-up study of patients with recent AMI, reduced fractal indices (α1 and β), and reduced HR turbulence predicted cardiac death when measured at the convalescent phase after AMI. Reduced β and turbulence slope predicted cardiac death when measured at 12 months after AMI. In the elderly population, β (p &lt; 0.001) and α1 (p &lt; 0.01) reduced significantly. Low-frequency power spectra were the only traditional measure of HR variability that decreased significantly during the 16-year period. HR variability is associated with many risk factors of atherosclerosis and with progression of CAD among patients with ischemic heart disease. Fractal HR dynamics are more sensitively able to detect age-related changes in cardiovascular autonomic regulation. Altered fractal HR dynamics and HR turbulence are associated with increased mortality after AMI.

oam1998@outlook.com / Background: Obstructive sleep apnea (OSA) is associated with increased mortality, for which impaired functional capacity (IFC) has been established as a surrogate. We sought to assess whether IFC is associated with increased mortality in patients with OSA and whether IFC is predictive of increased mortality after accounting for coronary artery disease. Methods: Patients with OSA who underwent both polysomnography testing and exercise stress echocardiogram were selected. Records were reviewed retrospectively for demographics, comorbidities, stress echocardiographic parameters, and polysomnography data. Univariable and multivariable logistic regression analysis was used to evaluate the association between IFC and overall mortality. We then evaluated the variables associated with IFC in the overall population and in the subgroup with normal Duke treadmill score (DTS). Results: In our cohort, 404 (26%) patients had IFC. The best predictors of IFC were female sex, history of smoking, ejection fraction less than 55, increased body mass index, presence of comorbidities, abnormal exercise echocardiogram, abnormal heart rate recovery, and abnormal DTS. Compared with those without IFC, patients with IFC were 5.1 times more likely to die (odds ratio [OR], 5.1; 95% confidence interval [CI], 2.5–10.5; P , 0.0001) by univariate analysis and 2.7 times more likely to die (OR, 2.7; 95% CI, 1.2–6.1; P = 0.02) by multivariate analysis, when accounting for heart rate recovery, DTS, and sleep apnea severity. Among those without coronary artery disease, patients with IFC were at significantly increased risk of mortality (OR, 4.3; 95% CI, 1.35–13.79; P = 0.0088) compared with those with preserved functional capacity. Conclusions: In our OSA population, IFC was a strong predictor of increased mortality. Among those with normal DTS, IFC identified a cohort at increased risk of mortality.

Magister Artium (Sport, Recreation and Exercise Science) - MA(SRES) / Over 45% of firefighter deaths are due to a sudden cardiac event caused by underlying coronary artery disease (CAD) risk factors that can be prevented through adequate CAD risk factor screening and management. The aim of the study was to determine the prevalence of CAD risk factors in firefighters in the City of Cape Town and the relationship between the various CAD risk factors. This study used a quantitative cross-sectional, descriptive and correlational design. A total of 124 full-time firefighters of the City of Cape Town (CoCT) Fire and Rescue Service were conveniently recruited to participate in the study, including males and females of all ethnicities. Coronary artery disease risk factor information was obtained with a CAD risk factor assessment form, including, past medical history, smoking status, physical activity behaviour, ethnicity/race, age and gender.

No description available.