published_or_final_version / Medicine / Master / Master of Research in Medicine

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Public Health / Master / Doctor of Medicine

Ischemic heart disease (IHD) is the most common cause of death around the world. The underlying cause of IHD is myocardial ischemia as a result of progressive narrowing of coronary arteries due to atherosclerosis with potential thrombotic complications mediated by platelets. In addition to the role in hemostasis, platelets are increasingly recognized as an important mediator in this atherothrombotic disease. Basic management of IHD lies on medical therapy and coronary revascularization procedures. Percutaneous coronary intervention (PCI) is a commonly used revascularization procedure in the treatment of IHD especially for relief and reduction of symptoms. On the other hand, antiplatelet therapy is often administrated to patients undergoing PCI in an attempt to prevent major adverse cardiac events (MACE) following the procedures. However not all patients respond to the same degree of the antiplatelet therapy and some still develop MACE or stent thrombosis in the presence of the treatment with antiplatelet drugs. Recently a flow cytometric-based assay has been developed to monitor the effect of the antiplatelet drug, particularly the P2Y12 receptor antagonist, in patients treated with this kind of drug. This assay measures the activity of platelets as platelet reactivity index (PRI) based on the phosphorylation state of an intracellular platelet protein called vasodilator stimulated phosphoprotein (VASP). The measured value of PRI is inversely related to the response of patient to the antiplatelet drug. In this study, the response of patients to the P2Y12 receptor antagonist Clopidogrel was investigated following PCI. The PRI of patients was found to be significantly lower than normal subjects without taking this drug, indicating the therapeutic effect of this drug on the patients. However nearly one-third of patients (17 out of 59) studied were found to be non-responsive to clopidogrel treatment based on a cut-off established in this study for classifying patients into responders or non-responders. Furthermore, significant difference between the two types of stents used in PCI procedure, namely bare metal stent (BMS) and drug eluting stent (DES), was observed in the study. Patients receiving DES had nearly three times higher percentage of being non-responsive to clopidogrel than the BMS counterpart (45% vs. 16%, p<0.028). This study provides evidence that DES may be implicated in the non-responsiveness or drug resistance of clopidogrel in patient undergoing PCI. / published_or_final_version / Pathology / Master / Master of Medical Sciences

University of Macau / Faculty of Science and Technology / Department of Electrical and Computer Engineering

D. Tech. Nursing / Cardiovascular disease is the most common and yet one of the most preventable causes of death in the world. Risk factors for cardiovascular disease are numerous and well known. These risk factors are amongst others, hypertension, diabetes, physical inactivity, obesity, smoking and behaviour patterns. The intention of the study was to use the concept of a wellness clinic to promote cardiovascular wellness in the community. Packaging multiple interventions in a single visit would enable the research team to identify risk factors and educate the person regarding their own risk factors. The objectives of the study were to determine the prevalence of risk factors for cardiovascular disease in Soshanguve, determine personnel time and direct cost for promoting cardiovascular wellness taking into consideration screening, diagnostic testing and teaching including time, travel and personnel; and develop the optimal package of cardiovascular wellness interventions as determined by a binary Integer Programming model that maximizes cardiovascular wellness subject to constrains of shortage of funds and human resources in a resource poor setting.

No description available.

No description available.

A thesis submitted to the School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfillment of the requirements for the degree of Doctor of Philosophy June 2017 Johannesburg, South Africa / Non-communicable diseases (NCDs) pose an increasing burden on public health and economic growth worldwide. The highest increase in prevalence and death rates of NCDs has been seen in low and middle-income countries (LMICs). World Health Organization (WHO) estimates that by 2030, NCDs will account for five times as many deaths as communicable diseases in LMICs and that there will be more than 2.16 billion overweight and 1.12 billion obese individuals in the world. It is also estimated that by 2020 NCDs will contribute 80 percent of the global burden of disease and the largest increase in NCD deaths will occur in Africa. Recent reports indicate that six of the ten leading natural causes of death in South Africa are NCDs. There are few studies that have used longitudinal data to understand the effects of life-course childhood adiposity on future health risks and the early life factors responsible for variations in lifecourse childhood obesity. However, it is not known whether there is a genetic basis for the variability in BMI developmental patterns over time. Lack of comprehensive longitudinal and genetic association data for obesity have made it difficult to do such studies in an African setting. It is still not clear whether the same genetic variants associated with obesity in Europeans and other populations are also associated with these traits in African populations. Understanding the genetic contribution to obesity in the black South African population may help to come up with effective interventions to deal with this emerging epidemic in Africa. The aim of this thesis was to better understand the contribution of genetics and explain the longitudinal genetic basis of childhood and adolescence obesity in black South African children. To deal with this, I firstly studied identification of distinct trajectories of BMI and then relate the established BMI trajectories to the future health risks of elevated blood pressure. Secondly, I explored the early life factors behind BMI trajectory membership, this would help to identify factors that may accelerate an individual’s progression from a normal BMI trajectory pattern membership to the one characterized with elevated BMI. Then lastly, I looked at the additive genetic effect for BMI and determine whether genetic risk of obesity in early adulthood was mediated by early life rapid growth. Results showed variation in BMI developmental patterns between boys and girls; three and four distinct sex-specific BMI trajectories were identified in boys and girls respectively. Children belonging to early onset overweight or obese BMI trajectories, characterized by elevated BMI, had an increased risk of elevated blood pressure in late adolescence, compared to their peers in the normal trajectories. Rapid conditional relative weight gain in early life was associated with increased risk of belonging to a BMI trajectory characterized by consistent elevated BMI over time. Individuals in overweight or obese trajectories had a higher chance of being overweight or obese in early adulthood. I found that a genetic risk score, based on known adult BMI Caucasian risk variants, showed significant longitudinal effects of genetic loci with BMI in childhood and adolescent and significant age-GRS interactions were observed. A higher genetic risk score predicted membership of early onset obese or overweight BMI trajectories. The genetic risk of obesity at 18 years of age was mediated by pre-adolescence and adolescence rapid weight gain. The results from this thesis emphasize the importance of studying individual’s BMI developmental patterns when studying development and progression of obesity. These findings also show that the information obtained from GWAS done in other populations can be equally relevant to African populations and this could be used in early identification of individuals at increased risk of obesity and other NCDs risk factors. Combing genetic risk score, BMI trajectories membership and weight status can be used to help improve the screening process of individuals to be targeted in coming up with targeted educational and behavior intervention programmes for obesity. These programmes should target individuals at risk at early stage in order to reduce the adverse health risk outcomes later in life. / MT 2017

Cardiovascular diseases (CVDs) remain to be the leading causes of morbidity and mortality in Hong Kong and worldwide. Among different modifiable risk factors, dietary pattern is on the major determinant for CVD and overall mortality. Other than pharmacological therapies for cardiovascular risk factors, such as hypertension, hyperlipidemia and diabetes, maintaining a healthy diet is a more sustainable method in general population to prevent CVDs. Current lifestyle intervention in the West countries focus on high intake of fruit and vegetables with more than 400g per day and limited saturated fats with less than 10% of energy, there is very limited data on impact of dietary pattern on CVDs in Chinese. Prior studies among Chinese in Hong Kong have shown that only half of the local population fell within these recommended ranges for fat, saturated fatty acid and cholesterol intakes. Several different dietary patterns have been recommended for CVDs prevention based on: i) food groups, such as Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet; ii) macronutrients: the low-carbohydrate diet, low glycemic index diet, very-low- fat diet and iii) nutrition or vitamin supplement. However, the effect of different dietary patterns based on modulations of food group, macronutrients and particular micronutrients on vascular structure and function in Chinese subjects is unclear. In the first part of this thesis, the relationships between different dietary pattern and surrogate markers of subclinical atherosclerosis and vascular function in different high risk populations for CVDs were investigated. In Chapter 3, we compared the assessment of dietary pattern in Chinese using different tool, including Food Frequency Questionnaire (FFQ); Dietary Record; and Dietitian assessment. In this study, we demonstrated that suitable dietary assessments tools should be chosen for the assessment of different dietary pattern, according to characteristics of assessments. In Chapter 4, the relationship between the fruit intake and subclinical atherosclerosis as measured by carotid intimal thickness (IMT) was investigated in patient with type II diabetes mellitus (DM). Our results showed that high fruit intake was associated with lower burden of carotid atherosclerosis, independent of level of vitamin intake in patients with type II DM. In Chapter 5, we compared the impact of high carbohydrate diet on arterial stiffness between control subjects without CVDs and patients with high risk for CVDs. Our findings showed that high carbohydrate diet mainly affected patients with established CVDs, and their increased arterial stiffness was associated with an elevation of blood pressure. In Chapter 6, we determined the effect of dietary vitamin intake on oxidative stress in patients with high risk of CVDs. In those high risk patients for CVDs, we demonstrated that increased dietary intake of vitamin A, beta-carotene and alpha tocopherol were associated with decreased oxidative stress, but these relationships were not observed in those control subjects without CVDs. It is likely attributed to the higher systemic oxidative stress levels in patients with high risk of CVDs. On the other hand, food intake may also affect the clinical efficacy of cardiovascular therapies. In particularly, it has been well established that herbal intake which is commonly used by Chinese can affect the anticoagulant effect of warfarin on patients with non-valvular atrial fibrillation (AF). Thus, in this second part of the thesis, we investigated the effect of concomitant herbal intake on anticoagulation control in patients with non-valvular AF treated with warfarin. Our results showed that patients with AF treated with warfarin had limited knowledge on potential interaction between herbal substances in foods and warfarin, in which increased herbal substances intake significantly reduced the percentage time of anticoagulant effect within the therapeutic range. Moreover, a single section of education on knowledge of herbal ingredients did not improve their percentage time of therapeutic range for these patients. In conclusion, these findings suggest that dietary pattern in Chinese might have significant impact of vascular function in patients with type II DM and high risk for CVDs. Moreover, the herbal substances in the diet among Chinese could have significant impact of the therapeutic effects in some of the cardiovascular medications, such as warfarin. Future clinical studies will be needed to confirm these potential beneficial effects of particular diet intake on vascular function in patients with high risks of CVDs as well as potential interaction between herbal substances in Chinese diet and cardiovascular medications. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy