[Truncated abstract] The main objective of this study was to develop and validate a demographic/epidemiologic Markov model for population modelling/forecasting of CARPs as well as CHD deaths and incidence in Western Australia using population, linked hospital morbidity and mortality data for WA over the period 1980 to 2000. A key feature of the model was the ability to count events as individuals moved from one state to another and an important aspect of model development and implementation was the method for estimation of model transition probabilities from available population data. The model was validated through comparison of model predictions with actual event numbers and through demonstration of its use in producing forecasts under standard extrapolation methods for transition probabilities as well as improving the forecasts by taking into account various possible changes to the management of CHD via surgical treatment changes. The final major objective was to demonstrate the use of model for performing sensitivity analysis of some scenarios. In particular, to explore the possible impact on future numbers of CARPs due to improvements in surgical procedures, particularly the introduction of drug eluting stents, and to explore the possible impact of change in trend of CHD incidence as might be caused by the obesity epidemic. ... When the effectiveness of PCI due to introduction of DES was increased by reducing Pr(CABG given PCI) and Pr(a repeat PCI), there was a small decline in the requirements for PCIs and the effect seemed to have a lag. Finally, in addition to these changes when other changes were incorporated which captured that a PCI was used more than a CABG due to a change in health policy after the introduction of DES, there was a small increase in the requirements for PCIs with a lag in the effect. Four incidence scenarios were developed for assessing the effect of change in secular trends of CHD incidence as might be caused by the obesity epidemic in such a way that they gradually represented an increasing effect of obesity epidemic (assuming that other risk factors changed favourably) on CHD incidence. The strategy adopted for developing the scenarios was that based on past trends the most dominant component of CHD incidence was first gradually altered and finally the remaining components were altered. iv The results showed that if the most dominant component of CHD incidence, eg, Pr(CHD - no history of CHD) levelled off and the trends in all other transition probabilities continued into future, then the projected numbers of CABGs and PCIs for 2001-2005 were insensitive to these changes. Even increasing this probability by as much as 20 percent did not alter the results much. These results implied that the short-term effect on projected numbers of CARPs caused by an increase in the most dominant component of CHD incidence, possibly due to an ?obesity epidemic, is small. In the final incidence scenario, two of the remaining CHD incidence components-Pr(CABG - no history of CHD) and Pr(CHD death - no CHD and no history of CHD) were projected to level off over 2001-2005 because these probabilities were declining over the baseline period of 1998-2000. The projected numbers of CABGs were more sensitive (compared to the previous scenarios) to these changes but PCIs were not.

Tam Wing Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 82-100). / Abstracts in English and Chinese. / English abstrac --- p.I / 中文摘要 --- p.VI / Glossary --- p.X / Chapter Chapter 1. --- Background: / Chapter 1.1. --- Coronary heart disease in Hong Kong --- p.1 / Chapter 1.2. --- Coronary heart disease and atherosclerosis --- p.2 / Chapter 1.3. --- Pathogenesis of atherosclerosis --- p.2 / Chapter 1.4. --- Risk factors for atherosclerosis --- p.5 / Chapter 1.5. --- Homocysteine --- p.6 / Chapter 1.6. --- Folate --- p.10 / Chapter 1.7. --- Vitamin B12 --- p.13 / Chapter 1.8. --- Adhesion Molecules --- p.14 / Chapter 1.9. --- Phytoestrogen --- p.17 / Chapter 1.10. --- Secondary prevention of coronary artery disease --- p.20 / Chapter Chapter 2. --- "Heart disease, Danshen and Gegen in Chinese medicine" / Chapter 2.1. --- The record of Cardiac symptoms in Chinese Medicine --- p.24 / Chapter 2.2. --- Danshen (Salvia Miltriorrhiza) --- p.25 / Chapter 2.3. --- Gegen (Radix Pueraria) --- p.28 / Chapter Chapter 3. --- Surrogate atherosclerotic markers / Chapter 3.1. --- Flow-mediated dilatation of brachial artery (FMD) --- p.31 / Chapter 3.2. --- Carotid intima media thickness (IMT) --- p.32 / Chapter Chapter 4. --- Method / Chapter 4.1. --- Rational of the study --- p.33 / Chapter 4.2. --- Clinical protocol --- p.35 / Chapter 4.3. --- Measurement of plasma homocysteine --- p.38 / Chapter 4.4. --- Measurement of folate and vitamin B12 --- p.40 / Chapter 4.5. --- Measurement of soluble cellular adhesion molecules (CAMs) --- p.41 / Chapter 4.6. --- Measurement of plasma enterolactone --- p.43 / Chapter 4.7. --- Measurement of plasma hs-C-reactive protein --- p.44 / Chapter 4.8. --- Other laboratory tests --- p.45 / Chapter 4.9. --- High resolution ultrasound imaging --- p.46 / Chapter 4.10. --- Statistical analysis --- p.49 / Chapter 4.11. --- My contribution to this joint project --- p.49 / Chapter Chapter 5. --- Results / Chapter 5.1. --- Recruitment and outcomes of subjects --- p.51 / Chapter 5.2. --- Baseline characteristics --- p.53 / Chapter 5.3. --- Medical history and treatment received in the study subjects --- p.54 / Chapter 5.4. --- Safety profiles --- p.55 / Chapter 5.5. --- Severe adverse events --- p.56 / Chapter 5.6. --- Lipid profiles --- p.57 / Chapter 5.7. --- Secondary endpoints --- p.58 / Chapter 5.8. --- Primary endopoints --- p.59 / Chapter 5.9. --- The effect of statin usage on the primary endpoints / Chapter 5.10. --- The major determinant of the change in FMD by multivariate logistic regression / Chapter 5.11. --- Progress of lipid profiles and primary endpoints in the open label phase / Chapter Chapter 6. --- Discussion / Chapter 6.1. --- Brachial FMD --- p.66 / Chapter 6.2. --- Carotid IMT --- p.69 / Chapter 6.3. --- Brachial GTN --- p.70 / Chapter 6.4. --- Lipid-lowering effect --- p.72 / Chapter 6.5. --- Phytoestrogen --- p.72 / Chapter 6.6. --- Folate --- p.73 / Chapter 6.7. --- Vitamin B12 and glucose --- p.76 / Chapter 6.8. --- Summary of possible anti-atherogenic mechanism of D&G --- p.76 / Chapter 6.9. --- Placebo effect --- p.77 / Chapter 6.10. --- Safety profile --- p.77 / Chapter 6.11. --- Limitation of the study and suggestion of solution --- p.77 / Chapter 6.12. --- Suggestions and ummary of the future work --- p.79 / Chapter Chapter 7. --- Conclusions --- p.81 / References --- p.82

Coronary heart diseases (CHD) remain the most prevalent cause of premature death. Ischemic hearts often result from coronary vasculature occlusion. Significant efforts have been made for the treatment of CHD, including medications and surgical procedures. Currently there are still no effective drugs or therapeutics available for the treatment of the disease. Growing new coronary vessels to naturally bypass narrowed/occluded arteries or forming sufficient collaterals to the ischemic region would lead to substantially improved blood perfusion and correction of ischemia. However, this aim remains a theoretical ideal due to the negligible ability to grow new coronary vessels even with current advances in therapeutic angiogenesis. In the present study, we have isolated and identified an active fraction of Geum japonicum (AFGJ) showing significant activity in induction of efficient coronary angiogenesis and heart function improvement. / In addition, proteomics methods were applied to investigate the protein alterations in CHD ischemic hearts and HUVECs. Two dimensional polyacrylamide gel electrophoresis (2-D PAGE) of the heart tissues of CHD rats showed 16 differentially expressed spots compared with sham and vehicle hearts, of which 8 were identified. Furthermore, 11 identified proteins of HUVECs treated with AFGJ or Angio-G at different time points were also observed by 2-D PAGE. The majority of identified proteins was found to be involved in the process of energy metabolisms. / In conclusion, these results have demonstrated therapeutic properties of AFGJ to induce early reconstitution of damaged coronary vasculature through both angiogensis and vasculogenesis. AFGJ treatments may provide a novel therapeutic modality for effective treatment of ischemic heart diseases. / The therapeutic effect of AFGJ on CHD through reconstitution of partially occluded coronary vessels in CHD animal models was demonstrated with underlying signaling mechanisms identified. Briefly, AFGJ could promote the proliferation of human umbilical vein endothelial cells (HUVECs) in vitro and the growth of new blood vessels or coronary collaterals in CHD models after 2-week treatment. The number of newly formed coronary vessels in treated hearts was more than that of vehicle treated hearts, as indicated by both MicroCT and histology analysis. Echocardiography studies demonstrated significant improvement of heart functions 2 weeks after treatment with AFGJ. Furthermore, ECG measurements showed that the altered ST segment in AFGJ treated CHD models almost had full recovery to a normal level while rats in the vehicle group consistently suffered from heart ischemia. Moreover, the results of MicroCT reconstruction directly demonstrated the reconstitution of the damaged coronary vessels with newly formed functional coronary collaterals, as illustrated by more blood vessels density (AFGJ vs vehicle [%]: 4.5+/-0.5 vs 2+/-0.35) and more branching points (AFGJ vs vehicle: 0.94+/-0.07 vs 0.65+/-0.10). These data suggest that AFGJ treatment significantly corrects the ischemia of the affected regions of the heart. / We also explored possible mechanisms underlying the effect of AFGJ. Firstly, AFGJ could induce mesenchymal stem cell (MSC) differentiation into vascular endothelial cells and the differentiated MSCs were involved in the tube formation. Secondly, Angio-G, the component derived from AFGJ, was able to stimulate significant proliferation of HUVECs in a dose dependent manner. Thirdly, in our tube-like capillary formation test of HUVECs in vitro, the length of formed tubes was greatly amplified with increasing concentration of Angio-G. Furthermore, the total length of Angio-G induced tubes was significantly reduced with increasing concentrations of AG490, an inhibitor of JAK/STAT pathways indicating possible involvement of the JAK/STAT signaling pathway. / Chen, Hao. / "December 2009." / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 136-145). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.