Au, Chun Ting. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves xxvii-lv). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT / In English --- p.ii / In Chinese --- p.v / LIST OF TABLES --- p.vii / ABBREVIATIONS / For Units --- p.ix / For Prefixes of the international system of units --- p.ix / For Terms commonly used in the report --- p.x / STATEMENT OF WORK DONE --- p.xvi / Chapter CHAPTER 1 --- Overview of Childhood Obstructive Sleep Apnea Syndrome (OSAS) / Chapter 1.1. --- Clinical Features of Childhood OSAS --- p.1 / Chapter 1.2. --- Definition of Childhood OSAS --- p.2 / Chapter 1.3. --- Prevalence of Childhood OSAS --- p.3 / Chapter 1.4. --- Pathophysiology --- p.4 / Chapter 1.5. --- Risk Factors --- p.6 / Chapter 1.6. --- Diagnosis --- p.10 / Chapter 1.7. --- Treatment / Chapter 1.7.1. --- Tonsillectomy and Adenoidectomy (T&A) --- p.12 / Chapter 1.7.2. --- Continuous Positive Airway Pressure (CPAP) --- p.14 / Chapter 1.7.3. --- Corticosteroids --- p.15 / Chapter 1.7.4. --- Leukotriene Receptor Antagonist --- p.16 / Chapter 1.8. --- Complications of Childhood OSAS / Chapter 1.8.1. --- Growth Failure --- p.17 / Chapter 1.8.2. --- Neurocognitive Abnormalities --- p.19 / Chapter 1.8.3. --- Cardiovascular Abnormalities --- p.20 / Chapter CHAPTER 2 --- Cardiovascular Complications of OSAS in Adults (Literature Review) / Chapter 2.1. --- Acute Effects of OSAS on Cardiovascular System --- p.21 / Chapter 2.2. --- Chronic Effects of OSAS on Cardiovascular System --- p.23 / Chapter 2.3. --- Hypertension --- p.24 / Chapter 2.4. --- Heart Failure --- p.28 / Chapter 2.5. --- Pulmonary Hypertension --- p.30 / Chapter 2.6. --- Arrhythmias --- p.31 / Chapter 2.7. --- Cardiac Ischemia and Vascular Disease --- p.33 / Chapter 2.8. --- Stroke --- p.34 / Chapter CHAPTER 3 --- Cardiovascular Complications of Childhood OSAS (Literature Review) / Chapter 3.1. --- Blood Pressure --- p.37 / Chapter 3.2. --- Ventricular Structure and Function --- p.40 / Chapter 3.3. --- Arterial Distensibility --- p.42 / Chapter 3.4. --- Heart Rate Variability --- p.42 / Chapter CHAPTER 4 --- Ambulatory Blood Pressure in Children with OSAS / Chapter 4.1. --- Introduction --- p.44 / Chapter 4.2. --- Methods / Chapter 4.2.1. --- Subjects and Study Design --- p.46 / Chapter 4.2.2. --- Polysomnography (PSG) --- p.47 / Chapter 4.2.3. --- Ambulatory Blood Pressure Measurement (ABPM) --- p.49 / Chapter 4.2.4. --- Statistical Analysis --- p.50 / Chapter 4.3. --- Results / Chapter 4.3.1. --- Subject Characteristics --- p.52 / Chapter 4.3.2. --- Blood Pressure during Wakefulness --- p.55 / Chapter 4.3.3. --- Blood Pressure during Sleep --- p.57 / Chapter 4.4. --- Discussion --- p.62 / Chapter 4.5. --- Conclusion --- p.70 / Chapter CHAPTER 5 --- Cardiac Remodeling and Dysfunction in Children with OSAS / Chapter 5.1. --- Introduction --- p.71 / Chapter 5.2. --- Methods / Chapter 5.2.1. --- Subjects and Study Design --- p.72 / Chapter 5.2.2. --- Polysomnography (PSG) --- p.74 / Chapter 5.2.3. --- Conventional Echocardiography --- p.75 / Chapter 5.2.4. --- Tissue Doppler Imaging --- p.76 / Chapter 5.2.5. --- Statistical Analysis --- p.77 / Chapter 5.3. --- Results / Chapter 5.3.1. --- Study Population --- p.79 / Chapter 5.3.2. --- Polysomnographic Findings --- p.79 / Chapter 5.3.3. --- Echocardiographic Findings / Chapter 5.3.3.1. --- Right Ventricle --- p.81 / Chapter 5.3.3.2. --- Left Ventricle --- p.83 / Chapter 5.3.4. --- Treatment Effect --- p.86 / Chapter 5.4. --- Discussion --- p.90 / Chapter 5.5. --- Conclusion --- p.95 / Chapter CHAPTER 6 --- Conclusion --- p.96 / APPENDIX I Hong Kong Children Sleep Questionnaire (Chinese) --- p.xvii / APPENDIX II Hong Kong Children Sleep Questionnaire (English) --- p.xxii / REFERENCES --- p.xxvii

目的：針對心血管初級預防，世界各國均推薦某一年齡段人群全部測量膽固醇以估算心血管病發病風險。此舉耗費高且非必須，本研究旨在建立並驗證一個新型的选择性膽固醇篩查模型，用以篩查需藥物治療之高危人群，并在成本效益方面與其它篩查模型相比較。 / 方法：本模型具體采用兩步法：首先利用一個足夠高的假設膽固醇值代入心血管病風險預測方程，用以系統性的高估絶大多數人的心血管病風險；其次只有假設心血管病風險高於推薦治療閾值時，該個體才需要測量膽固醇，並進行實際心血管病風險分析。 / 英国健康调查和中国营养与健康调查是本次研究的合适数据。我們首先探索最優的假設膽固醇值，尋找到最後膽固醇值之後，我們將繼續測試我們的新型膽固醇篩查模型，在不同的治療閾值下，表現是否穩定。我們以靈敏度，特異度和徐篩查人群為指標，比較我們模型與全民篩查模型和英國NICE 選擇篩查模型相比較。之後我們估算在中英人群中應用該篩查模型，所需耗費的成本和可預防心血管事件數。 / 结果：與全名篩查模型相比，我們的模型靈敏度相若但可以節省80%左右的篩查費用。模型的靈敏度主要取決於所採用的假設膽固醇值，與所用風險預測方程，治療閾值和人群心血管風險分佈無關。當以均數加2 倍標準差作為假設膽固醇值時，靈敏度可達到97.5%左右，特異度可以達到90%左右，符合預期。模型應用於中國人群得到的結果類似。值得註意的是，在中國人群中，即使不測量膽固醇，模型靈敏度亦接近95%。此外，將膽固醇篩查項目限制于男性50-84歲，女性60-84 歲年齡段可以進一步減少篩檢費用。在人群影響方面，我們模型可預防心血管事件數比全名篩查模型略少，但成本大大降低。英國NICE 模型適用於某些特定情況，但並非全部。 / 結論：我們的新型篩查模型靈敏度與全民篩查模型相若，但可以節省大量篩查費用。在资源匮乏地区，可考虑在某一特定年龄段运用我们的模型已达到进一步减少费用的效果。如果本研究结果得到进一步数据证实，對於中國人群而言，膽固醇測量可能並非心血管風險評估所必須。 / Objectives / Since the mid 1990s, most guidelines on primary prevention of cardiovascular disease (CVD) have recommended regular cholesterol measurement for all adults or those above a certain age (which is known as mass screening). Cholesterol measurement comprises a large cost of CVD prevention and is not necessarily required in those who do not need drug intervention. In order to reduce this cost, we have developed a new selective cholesterol screening model in order to determine whose cholesterol should be measured for drug prevention. The model was evaluated and compared with other widely adopted models in basic model performance as well as cost effectiveness. / Methods / The new model has two steps. In the first step, we purposely over-estimated the majority of respondents’ CVD risk by substituting a sufficiently high hypothetical cholesterol value in the risk estimation. We then recommend cholesterol measurement only to those with the estimated CVD risk above a predetermined risk threshold for drug treatment. In the second step, the CVD risk is re-estimated based on the individual’s real cholesterol consentration. Those with a risk above the treatment threshold are recommended for drug treatment. / We evaluated the performance of our two-step model with data from the Health Survey for England and re-evaluated it with data from the China Nutrition and Health Survey 2002. By varying the hypothetical cholesterol values and treatment thresholds in CVD risk, we assessed the sensitivity, specificity and proportion of the population who need to measure cholesterol and compared it with the US mass screening model and the UK NICE selective screening model. We further compared the costs and CVD events avoided in the compared screening programmes. We also examined how the age restriction should be set in cholesterol screening programmes. / Results / As compared to mass screening, our new model can achieve a high sensitivity and save some 80% the cost of cholesterol measurements. The sensitivity depends mainly on the hypothetical cholesterol level used and seems independent of population’s CVD risk, treatment cut-off values and risk prediction model. The model performed well in almost all the conditions tested. When the hypothetical cholesterol was set at MEAN+2SD, the resulting sensitivity of our selective screening model was almost always above 95% and close to the expected 97.5%. The sensitivity was only compromised slightly if cholesterol is not measured at all for the Chinese population. Furthermore, in order to save more costs, cholesterol measurement could be better restricted to men aged 50-84 and women 60-84 years regardless of the screening model used. In CVD events prevented, mass screening is always the best but our model can prevent almost as many. In costs, mass screening is always the most expensive but our model can save all or most of the cost. The NICE selective model can perform as well as our model only when it is used in an appropriate manner and in certain circumstances. / Conclusion / Our new cholesterol screening model has a high sensitivity which is comparable to that of universal screening programs but can save most of the cost on cholesterol measurements. In where resources are particular sparse, our model can also perform well by applying it only to certain age groups, which will further save cholesterol measurement costs. Cholesterol measurement could even be completely avoided for the Chinese population if our findings can be re-confirmed correct with more updated data. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Hu, Xuefeng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 114-121). / Abstract also in Chinese. / Abstract (in English) --- p.i / Abstract (in Chinese) --- p.iv / Acknowledgements --- p.vi / Abbreviations used in the thesis --- p.viii / List of Tables --- p.xvi / List of Figures --- p.xviii / List of Boxes --- p.xix / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- The burden of cardiovascular disease --- p.1 / Chapter 1.2 --- Primary prevention of CVD --- p.2 / Chapter 1.3 --- The high-risk individual strategy for CVD primary prevention --- p.3 / Chapter 1.3.1 --- The high risk individual strategy is effective --- p.4 / Chapter 1.3.2 --- The high risk individual strategy is cost-effective --- p.4 / Chapter 1.4 --- Who should be treated with drugs? --- p.5 / Chapter 1.4.1 --- The single risk factor strategy --- p.5 / Chapter 1.4.2 --- The overall CVD risk strategy --- p.7 / Chapter 1.4.3 --- Scope of CVD primary prevention --- p.8 / Chapter 1.5 --- Methods for assessing the CVD risk --- p.9 / Chapter 1.6 --- Current strategies for cholesterol measurements --- p.10 / Chapter 1.6.1 --- United States National Cholesterol Education Program --- p.13 / Chapter 1.6.2 --- American Heart Association CVD and Stroke prevention guideline --- p.14 / Chapter 1.6.3 --- The U.S. Preventive Services Task Force guideline --- p.15 / Chapter 1.6.4 --- New Zealand guideline 2003 --- p.16 / Chapter 1.6.5 --- Australian guideline 2009 --- p.17 / Chapter 1.6.6 --- The Joint British Society guideline-2 --- p.17 / Chapter 1.6.7 --- UK Department of Health guideline on vascular check --- p.18 / Chapter 1.6.8 --- China Blood Lipid Modification Guideline 2007 --- p.18 / Chapter 1.6.9 --- Summary of the reviewed guidelines --- p.19 / Chapter 1.7 --- Rationale for a selective screening model --- p.20 / Chapter 1.8 --- The UK NICE model --- p.22 / Chapter 1.9 --- Objectives of this study --- p.24 / Chapter 2 --- Methods --- p.25 / Chapter 2.1 --- The new cholesterol screening model --- p.25 / Chapter 2.2 --- Framework for evaluating the new screening model --- p.27 / Chapter 2.3 --- Indexes for evaluating the basic performance of screening models --- p.28 / Chapter 2.3.1 --- Sensitivity, specificity and % need cholesterol measurement --- p.28 / Chapter 2.3.2 --- Sensitivity analysis for model performance --- p.29 / Chapter 2.3.2.1 --- Using different hypothetical cholesterol values --- p.29 / Chapter 2.3.2.2 --- Using different treatment cut-off thresholds --- p.30 / Chapter 2.3.2.3 --- Using different populations --- p.30 / Chapter 2.3.2.4 --- Using different risk equations --- p.31 / Chapter 2.4 --- Data --- p.31 / Chapter 2.4.1 --- The Health Survey for England --- p.31 / Chapter 2.4.1.1 --- Background and aim of the survey --- p.31 / Chapter 2.4.1.2 --- Survey design --- p.32 / Chapter 2.4.1.2.1 --- Sampling Frame --- p.32 / Chapter 2.4.1.2.2 --- Weighting variables --- p.33 / Chapter 2.4.1.3 --- Data collection --- p.33 / Chapter 2.4.1.3.1 --- Blood cholesterol --- p.34 / Chapter 2.4.1.3.2 --- Blood pressure --- p.34 / Chapter 2.4.1.3.3 --- Smoking --- p.34 / Chapter 2.4.1.3.4 --- History of CVD and diabetes --- p.34 / Chapter 2.4.1.3.5 --- Treatment history --- p.35 / Chapter 2.4.2 --- The 2002 China National Nutrition and Health Survey --- p.35 / Chapter 2.4.2.1 --- Survey design --- p.36 / Chapter 2.4.2.2 --- Data collection --- p.36 / Chapter 2.4.2.2.1 --- Blood pressure --- p.36 / Chapter 2.4.2.2.2 --- Blood cholesterol --- p.38 / Chapter 2.4.2.2.3 --- Smoking --- p.38 / Chapter 2.4.2.2.4 --- History of CVD, diabetes and drug treatment --- p.38 / Chapter 2.4.3 --- Subjects eligible for analysis in this study --- p.38 / Chapter 2.5 --- CVD risk prediction --- p.43 / Chapter 2.5.1 --- The Framingham risk equation for the UK population --- p.43 / Chapter 2.5.2 --- The Asian equation for the Chinese population --- p.44 / Chapter 2.5.3 --- Adjusting for cholesterol and blood pressure --- p.45 / Chapter 2.5.4 --- Deriving the hypothetical cholesterol --- p.46 / Chapter 2.6 --- Identifying the appropriate age ranges for cholesterol measurement --- p.47 / Chapter 2.7 --- Comparing various screening models and options --- p.47 / Chapter 2.7.1 --- Compared screening models and options --- p.47 / Chapter 2.7.1 --- Indices for the performance of the screening options --- p.49 / Chapter 2.7.2 --- Costs of different screening options --- p.50 / Chapter 2.7.2.1 --- Components of screening cost from societal perspective --- p.50 / Chapter 2.7.2.1.1 --- Cost for inviting people for data collection --- p.50 / Chapter 2.7.2.1.2 --- Cost for the full risk assessment --- p.51 / Chapter 2.7.2.1.3 --- Treatment cost --- p.51 / Chapter 2.7.2.1.4 --- Cost saved for avoided CVD events --- p.52 / Chapter 2.7.2.2 --- Components of screening cost from health system’s perspective --- p.52 / Chapter 2.7.3 --- Number of CVD events avoidable --- p.53 / Chapter 2.8 --- Statistical analysis --- p.54 / Chapter 2.8.1 --- Descriptive analysis --- p.54 / Chapter 2.8.2 --- Cross-tabulation analysis --- p.54 / Chapter 2.8.3 --- Survey data analysis --- p.54 / Chapter 3 --- Results --- p.57 / Chapter 3.1 --- Description of data --- p.57 / Chapter 3.1.1 --- The UK population --- p.57 / Chapter 3.1.1.1 --- Sumamry of CVD risk and risk factors --- p.57 / Chapter 3.1.1.2 --- Distribution of age --- p.57 / Chapter 3.1.1.3 --- Distribution of blood pressure and blood cholesterol --- p.58 / Chapter 3.1.1.4 --- Distribution of the predicted 10-year CVD risk --- p.62 / Chapter 3.1.1.5 --- Relation between the risk threshold and age --- p.63 / Chapter 3.1.2 --- The Chinese population --- p.65 / Chapter 3.1.2.1 --- Summary of CVD risk and risk factors --- p.65 / Chapter 3.1.2.2 --- Distribution of age --- p.65 / Chapter 3.1.2.3 --- Distribution of blood pressure and blood cholesterol --- p.66 / Chapter 3.1.2.4 --- Distribution of the predicted 10-year CVD risk --- p.69 / Chapter 3.1.2.5 --- Relation between the risk threshold and age --- p.70 / Chapter 3.2 --- Performance of our new screening model --- p.72 / Chapter 3.2.1 --- Performance according to cholesterol values in the UK population --- p.72 / Chapter 3.2.2 --- Performance according to treatment cut-offs in the UK population --- p.73 / Chapter 3.2.3 --- Performance according to cholesterol values in the Chinese population --- p.73 / Chapter 3.2.4 --- Performance according to the risk cut-offs in the Chinese population --- p.74 / Chapter 3.2.4 --- Performance using different risk equations --- p.76 / Chapter 3.3 --- Comparison with other existing screening models --- p.77 / Chapter 3.3.1 --- Performance of the 3 models within an age-restricted UK population --- p.79 / Chapter 3.3.2 --- Performance of the 3 models within an age-restricted Chinese population --- p.81 / Chapter 3.3.3 --- Performance of the 3 models in the entire UK population --- p.83 / Chapter 3.3.4 --- Performance of the 3 models in the entire Chinese population --- p.84 / Chapter 3.3.5 --- Costs of various screening options --- p.87 / Chapter 3.3.6 --- Number of CVD events avoidable of the screening programmes --- p.92 / Chapter 4 --- Discussion --- p.96 / Chapter 4.1.1 --- Performance at different hypothetical cholesterol values --- p.96 / Chapter 4.1.2 --- Performance at various treatment cut-off thresholds --- p.97 / Chapter 4.1.3 --- Performance with different risk equations --- p.98 / Chapter 4.1.4 --- Performance in different populations --- p.99 / Chapter 4.1.5 --- Performance with different survival functions --- p.99 / Chapter 4.2 --- Further modifications of the model --- p.100 / Chapter 4.2.1 --- A model without any cholesterol measurement --- p.100 / Chapter 4.2.2 --- Age restriction for selective models --- p.102 / Chapter 4.2.3 --- Our model with potential personalized treatment cut-off --- p.103 / Chapter 4.2.4 --- Three key things to ensure model performance in other population --- p.104 / Chapter 4.3 --- CVD events preventable --- p.105 / Chapter 4.3.1 --- Importance of age restriction --- p.105 / Chapter 4.3.2 --- Limitations of the NICE model --- p.106 / Chapter 4.4 --- Costs of different screening models --- p.107 / Chapter 4.4.1 --- Cost from different perspectives --- p.107 / Chapter 4.4.2 --- Cholesterol measurement cost and routine data collection --- p.108 / Chapter 4.4.3 --- Cost components --- p.109 / Chapter 4.4.4 --- Ways to reduce cholesterol measurement costs --- p.109 / Chapter 4.4.5 --- Costs and gain of the missing 2.5% high risk individuals --- p.109 / Chapter 4.5 --- Strengths and limitations of this study --- p.110 / Chapter 4.6 --- Recommendations --- p.113 / References --- p.114

Sociopolitical and economic factors shape the lived experience of immigrants and subsequent US-born generations. Often marked by immigrant-related federal and subfederal (i.e., state, county, and city) government policies, but also inclusive of public sentiment toward immigrants, an anti-immigrant climate limits Latino immigrants’ and US-born Latinos’ access to pro-health resources and services, keeps them in a lower socioeconomic position, increases their exposure to interpersonal and structural discrimination, and directly and indirectly exposes them to acute and chronic stressors that can take a toll on their cardiovascular health. The objective of this dissertation is to examine the association between anti-immigrant climate, first defined using policies and then defined using anti-Latino immigrant sentiment, and a panel of traditional and non-traditional cardiovascular disease risk factors among immigrant and US-born Latino adults living in the United States. This dissertation is organized into five sections: 1) an introduction, 2) a systematic review and critical analysis of the literature on US federal and subfederal policies and physical and mental health outcomes among Latino adults, 3) an empirical study of subfederal immigrant-related policies enacted in 2007 and their association with a panel of cardiovascular disease risk factors among Latino adult participants in the National Health Interview Survey, 4) an empirical study of anti-Latino immigrant sentiment during the 2016 Presidential campaign and election and a panel of incident cardiovascular disease risk factors in a cohort of Latino participants of the Hispanic Community Health Survey/Study of Latinos, and 5) a discussion of findings and implications for future research. The systematic review did not identify any studies of immigrant-related policies and traditional cardiovascular disease health condition risk factors of obesity, hypertension, high cholesterol, or diabetes. Exclusionary policies were associated with poor mental health and poor self-rated health and no relationship between policies and adverse birth outcomes was observed. In the empirical study of subfederal immigrant-related policies, I did not observe a statistically significant association between exposure to exclusionary policy climates in 2007 and a greater increase in the prevalence of cardiovascular disease risk factors relative to exposure to neutral/inclusive policy climates. Although no statistically significant difference-in-differences were observed, Latinos living in exclusionary states had a statistically significant increase in the prevalence of high alcohol consumption one year after exposure, while the prevalence remained unchanged among Latinos living in neutral/inclusive states. This increase was reflective of increases among foreign-born Latinos, not US-born Latinos. In the empirical study of anti-Latino immigrant sentiment during the 2016 Presidential campaign and election, findings from models of high depressive symptoms suggested that among Latinos of Mexican and Central American background, the exposed were more likely to have incident high depressive symptoms than the unexposed. Findings also suggested an association between exposure status and incident current alcohol use, particularly among the foreign-born. An inverse association between exposure and risk of hypertension was observed, with further differences by duration of US residence. Patterns for alcohol consumption across both empirical studies suggest that future studies should continue to explore the effect of anti-immigrant climate on acute changes in alcohol consumption among Latinos in the US. Additionally, findings from the systematic review and the second empirical study also support the continued study of the relationship between anti-immigrant climate and mental health outcomes. As the sociopolitical climate of the US becomes increasingly harsh toward Latino immigrants and their families, studies should examine other health outcomes in order to understand which dimensions of health are affected by exposure to an anti-immigrant climate among one of the largest ethnic populations in the US.

[Truncated abstract] Vitamin E is comprised of a family of tocopherols (TOH) and tocotrienols. The most studied of these is [alpha]-tocopherol ([alpha]-TOH), as this form is retained within the body and any deficiency of vitamin E is corrected with this supplement. [alpha]-TOH is a lipid-soluble antioxidant required for the preservation of cell membranes and potentially acts as a defense against oxidative stress. Individuals who have a primary vitamin E deficiency such as low birth weight infants, secondary vitamin E deficiency due to fat malabsorption such as in abetalipoproteinaemia, or a genetic defect in TOH transport require supplementation. There is debate as to whether vitamin E supplementation in other patient groups is required. Vitamin E supplementation has been recommended for persons with FHBL, a rare disorder of lipoprotein metabolism that leads to low serum [alpha]-TOH and decreased LDL cholesterol and apolipoprotein B concentrations. We examined the effect of truncated apoB variants on vitamin E metabolism and oxidative stress in persons with heterozygous FHBL. We used HPLC with electrochemical detection to measure [alpha]- and [gamma]-TOH in serum, erythrocytes, and platelets, and GC-MS to measure urinary F2-isoprostanes and TOH metabolites as markers of oxidative stress and TOH intake, respectively. Erythrocyte [alpha]-TOH was decreased, but we observed no differences in lipid-adjusted serum TOHs, erythrocyte [gamma]-TOH, platelet [alpha]- or [gamma]-TOH, urinary F2-isoprostanes, or TOH metabolites. Taken together, our findings do not support the recommendation that persons with heterozygous FHBL should receive vitamin E supplementation. ... Sesame lignans are natural components of sesame seed oil and there is evidence that these lignans can inhibit CYP450 enzymes, in particular, those responsible for vitamin E metabolism. We hypothesised that sesame seed ingestion would increase serum [gamma]-TOH, lower plasma lipids and inhibit platelet function in human subjects with at least one cardiovascular risk factor. We used HPLC with electrochemical detection to measure [alpha]- and -TOH in serum and GC-MS to measure F2-isoprostanes and TOH metabolites as markers of oxidative stress and TOH intake, respectively. We used high-sensitive C-reactive protein as a measure of systemic inflammation. Platelet function was assessed using the PFA-100 platelet aggregation assay. Although serum [gamma]-TOH increased by 17%, we observed no effect on lipid metabolism, markers of inflammation, oxidative stress or platelet function following treatment with ~25 g/day sesame seeds for five weeks. Our findings challenge the hypothesis that sesame seed ingestion provides beneficial cardiovascular effects. In summary, we have studied the metabolism and transport of both [alpha]- and [gamma]-TOH in humans to evaluate the requirements for supplementation and the effects of vitamin E on platelet function and CYP3A4 activity. Specialised techniques using HPLC were developed to measure serum and cellular TOH concentrations both in supplemented and un-supplemented individuals. We also used GCMS to provide a sensitive, accurate assessment of TOH metabolites and midazolam pharmacokinetics in humans after vitamin E supplementation. We have examined the role vitamin E has on important biochemical endpoints, with emphasis on the implications for TOH supplementation in subjects at risk of CVD.

University of Macau / Institute of Chinese Medical Sciences

Atherosclerosis is a vascular degenerative disease leading to progressive thickening in the intima of large and medium sized arteries through the formation of plaque that is very rich with cholesterol. The cholesterol is carried by LDL (low density lipoprotein) particles which pass through the endothelium and accumulate in the intima. The passage of LDL is influenced by wall shear stress which activates physiological responses of the endothelium. However, the causal relationship between the physiological responses and their effect on LDL mass transport is not fully understood. To obtain blood flow patterns in human carotid arteries, a fluid structure interaction (FSI) computational approach is employed, based on the in-vivo arterial geometry constructed from black blood magnetic resonance images (BBMRI) and flow rate boundary conditions obtained from phase contrast images (PC). Wall shear stress (WSS) on the luminal surface is computed, and this variable is related to the formation of leaky junctions, which is a major transendothelial pathway for LDL. A model for the fraction of leaky junction at a surface is incorporated into the overall computational scheme for mass transport, along with pore theory. The theoretical model is applied to images from three human carotid arteries in which the degree of disease ranges from mild to moderate. Maximum mass flux is predicted to be in the downstream region of stenoses where WSS is low, and this result is consistent with the clinical observation of plaque progression downstream of the stenosis. The hypothesis that the majority of LDL enters into the intima through leaky junctions is supported by observation of similar distributions between the pattern of volume flux via leaky junctions and mass flux. These studies suggest that mass flux of LDL can be a predictor to indicate areas with potential for plaque formation and progression in human carotid artery disease.

Imaging guidance may allow minimally invasive alternatives to open surgical exposure and help reduce procedure risk and morbidity. The inherent vascular and soft-tissue contrast of MRI make it an appealing imaging modality to guide cardiovascular interventional procedures. Advances in real-time MRI have made MRI-guided procedures a realistic possibility. The MR environment, however, introduces additional challenges to the development of compatible, conspicuous and safe devices. The overall goal of this work was to enable selected MRI-guided cardiovascular interventional procedures with clearly visible MR devices. In the first part of this work, we developed actively visualized devices for three distinct MRI-guided interventional procedures and techniques to assess their signal performance. We then investigated factors influencing complex device safety in the MR environment and evaluated a technique to better determine and monitor potential device heating. This input contributed to the development of a system to further improve device safety with continual device monitoring and dynamic scanner feedback control. In the final part of this work, we demonstrated the utility of MRI guidance and actively visualized devices to enable traditional and complex cardiovascular access. Together these provide important elements to bring MRI-guided cardiovascular interventional procedures closer to clinical implementation.

University of Macau / Institute of Chinese Medical Sciences

No abstract available. / Thesis (M.D.)-University of Natal, 1973.

Understanding variability of heath status is highly likely to be an important component of personalized medicine to predict health status of individuals and to promote personal health. Evidences of Genome Wide Association Study and gene expression study indicating that genetic factors affect the risk susceptibility of individuals have suggested adding genetic factors as a component of health status measurements. In order to validate or to predict health risk status with collected personal data such as clinical measurements or genomic data, it is important to have a well-established profile of diseases. The primary effort of this work was to find genomic evidence relevant to coronary artery disease. Two major methods of genomic analysis, gene expression profiling and GWAS on gene expression, were performed to dissect transcriptional and genotypic fingerprints of coronary artery disease. Blood-informative transcriptional Axes that can be described by 10 covariating transcripts per each Axis were utilized as a crucial measure of gene expression analysis. This study of the relationship between gene expression variation and various measurements of coronary artery disease delivered compelling results showing strong association between two transcriptional Axes and incident of myocardial infarction. 244 transcripts closely correlated with death by cardiovascular disease related events were also showing clear association with those two transcriptional Axes. These results suggest potential transcripts for use in risk prediction for the advent of myocardial infarction and cardiac death.