Introduction There has been much discussion on personalised medicine; however use of genotype in risk prediction for coronary heart disease (CHD) has not resulted in appreciable improvements over non-genetic risk factors. The primary aim was to determine whether candidate single nucleotide polymorphisms (SNPs) identified from genome-wide association studies improved prediction of CHD over conventional risk factors (CRF). The secondary aim was to determine whether the use of apolipoproteins or lipoprotein(a) improved risk prediction of CHD. Methods Analyses used the Edinburgh Heart Disease Prevention Study (EHDPS), with 1592 men aged 30-59 and follow-up after 20 years; and the Edinburgh Artery Study (EAS), with 1592 men and women aged 54-75 and 15 years of follow-up. Candidate SNPs were identified by systematic literature reviews. CHD status was evaluated as severe (myocardial infarction or coronary revascularisation), and any (severe CHD, angina or non-specified ischaemic heart disease). Cox proportional hazards models were used to evaluate addition of candidate SNPs or lipids to models containing CRF. Results A group of genome-wide significant SNPs resulted in a non-significant improvement in C-index for severe CHD (0.038, p=0.082), and a significant improvement in C-index for any CHD (0.042, p=0.016); the associated net reclassification improvements (NRI) were 20.5% and 18.7%, respectively. Regression trees identified SNPs that were predictive of the remaining variance after adjusting for CRF; this resulted in a significant improvement in C-index for any CHD (0.031, p=0.008). The NRI were 11.0% and 9.6% for severe and any CHD, respectively. When compared with HDL cholesterol/total cholesterol, apolipoprotein AI/total cholesterol yielded a NRI of 3.3% for severe CHD. Lipoprotein(a) improved prediction of severe CHD, with a non-significant improvement in C-index (0.020, p=0.087), and NRI of 11.8%. Conclusion The results of this study indicate that a well selected group of candidate SNPs can improve risk prediction for CHD over-and-above CRF. The inclusion of lipoprotein(a), along with CRF, appeared to improve prediction of severe CHD, but not any CHD.

Giant Cell arteritis (GCA) is a systemic inflammatory disease that affects arteries of medium- and large size. Symptoms of GCA such as headache and fever usually promptly improve with treatment of glucocorticoids. Apart from advanced age, female sex and Northern-European descent, risk factors for GCA are unknown. Most studies have found that life expectancy for patients with GCA is not reduced compared with the general population and studies on cardiovascular disease in GCA have provided conflicting results. Data for the studies of this thesis are drawn from the Reykjavik Study (RS) that is a general population-based cohort study with continuous surveillance for coronary heart disease and vital status. Subjects born in 1907–1934 and living in Reykjavik, Iceland or adjacent communities in 1966 were invited for study visit from 1967-1994. Information on cardiovascular risk factors were collected at study visit. Diagnosis of GCA for this study was based on re-examination of all temporal arteries biopsies (TAB) from members of the RS cohort; however, information was also obtained from the original pathology report. Of 19,360 subjects included in the RS, 194 developed GCA during the follow-up period. Body mass index was inversely associated with the occurrence of GCA. Among men, but not women, hypertension was associated and smoking inversely associated with the occurrence of GCA. Among women, but not men, GCA was associated with coronary heart disease. Subjects with GCA had approximately 50% increase in mortality risk compared with the general population. Increase mortality was mainly observed among GCA patients based on the diagnosis of re-examination of TAB; however, no such an association was found if diagnosis of GCA was made based on the original pathology report. Those subjects were likely not clinically diagnosed with GCA, signaling that treatment for GCA might be beneficial with respect to mortality risk.

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It is consistently documented in the literature that Asian Indians are at high risk of coronary heart disease and this risk is exacerbated among migrant Asian Indians globally. Asian Indians have a premature, markedly severe and malignant course of coronary heart disease. This study was built on the premise that in order to provide culturally competent and sensitive care for migrant Asian Indians with coronary heart disease in a multicultural society such as Australia, it is important to explore migrant Asian Indians’ experiences, risk factor knowledge and health beliefs and behaviours in relation to coronary heart disease. Findings indicate the need for health promotion and cardiac illness prevention programs that use intervention models of health behaviour change and are sensitive to the needs of migrants from Asian Indian culture. The major limitation of the study was that the data obtained were from a group of tertiary-educated migrant Indians. Future studies should explore the coronary heart disease perspectives of migrant Indians with different education levels and from the perspective of second-generation Indians in Australia. / Doctor of Philosophy (PhD)

Acute coronary syndrome (ACS), the acute manifestation of coronary heart disease (CHD), is the leading cardiovascular cause of mortality and morbidity globally, and represents one of the most common causes of acute medical admissions to Australian hospitals. Following medical and/or surgical management of ACS, lifestyle modification to reduce the underlying risk factors that contribute to the progression of the disease remains vital. Cardiac rehabilitation (CR) has been widely accepted as an intervention that can reduce mortality and modify risk factors for subsequent coronary events and cardiovascular disease. While the benefits of cardiac rehabilitation programs have been demonstrated, participation and adherence to these programs remain low for various reasons, particularly among patients whose treatment includes revascularisation with percutaneous coronary intervention. This method of revascularisation has become increasingly common due its immediate success, rapid procedural technique, short hospital stay and early return to work for patients of working age. The aim of this study was to develop and test the feasibility of an evidence-based health-related lifestyle management program for risk factor modification in patients with ACS undergoing percutaneous coronary intervention. Four distinct yet interrelated studies were undertaken as part of the Development and evaluation of a Health-related Lifestyle self-Management (HeLM) intervention for patients with ACS Project. Three of these studies informed the development of the HeLM intervention, which was based on the principles of chronic disease self-management and evidence-based practice that included best evidence from the literature, clinical expertise and patient preferences. The first study was a systematic review of the literature to identify the best available evidence of the effect of brief interventions for lifestyle modification in patients with CHD. Findings from the 17 trials included in the systematic review, although inconclusive suggest that brief structured interventions can have beneficial effects on risk factor modification and consequently on progression of CHD. The second study was a qualitative interview of CR coordinators to identify from their clinical expertise the influence of the Reducing Risk in Heart Disease guidelines on practice: the Implementation of the Cardiac Evidence-Based Reducing Risk in Heart Disease Guidelines (ICEBRG) study. Findings from this study indicated limited implementation of the guidelines due to various barriers relating to health services, CR programs, professional practice and the patient and their families. Despite these barriers, it was evident that CR coordinators were striving to overcome these odds and provide evidence-based care. The third study undertaken to identify patient preferences for CR was the Follow-up After percutaneous Coronary Treatment (FACT) Study. The findings indicated that although the majority of the participants had two or more risk factors, they lacked knowledge of the link between risk factors and CHD, and less than a third had attended CR. The main reasons for nonattendance included timing, distance to travel, length of program, work commitments and lack of motivation to attend the programs. Their suggestions for improvement included telephone follow-up and flexibility of the CR programs. This study also informed the development of a tool that can be used by clinicians to flag patients who are unlikely to attend traditional CR. Identification of these people will allow alternate strategies to reduce risk factors to be tailored to their needs. The findings from these three studies were used to develop the HeLM intervention. The final study was undertaken to assess the feasibility of the HeLM intervention that was based on evidence compared to standard treatment for promoting lifestyle modification. This study was undertaken in 51 participants who were followed up two weeks following the completion of the intervention. The findings demonstrated that patients found the information beneficial and were pleased to receive it in their homes. The telephone support was also extremely well received. The study enabled the program and the process for implementation to be refined and indicated that a large multicentre trial would be feasible. The HeLM may be a strategy that could reach patients who have thus far eluded traditional CR programs and support them to make the necessary lifestyle changes. It may also be an adjunct to traditional CR and have a synergistic effect in facilitating health-promoting behaviours in CHD patients. Studies of interventions for risk factor modification in participants with CHD require longer term follow-up to assess the effect of the intervention in the sustainability of behaviour modification. Further research is necessary to evaluate the long-term effects as well as the cost effectiveness of the intervention. / Doctor of Philosophy (PhD)

Coronary Heart Disease (CHD) is a major cause of death in Western countries. Mediterranean and Asian populations have a lower risk of death from CHD compared to Westernised population, as do vegetarian versus omnivorous populations. Dietary constituents of traditional diets consumed by these populations are thought to influence both the classical risk factors for CHD, and the more recently identified risk factors, such as oxidative modification of low density lipoprotein (LDL), LDL particle size, arterial compliance and haemostatic factors. The aim of this thesis was to examine the effects of several food components, particularly soybean and monounsaturated fat (MUFA), on CHD risk factors through 3 carefully controlled dietary interventions, and a cross-sectional study. A randomised crossover dietary intervention study was conducted in 42 healthy males to investigate the effect on CHD risk factors of replacing lean meat with tofu, a soybean product regularly consumed by Asian populations, while controlling all other dietary factors. The tofu diet resulted in significantly lower total cholesterol and triacylglycerol levels compared to the lean meat diet, and LDL particles that were more resistant to in vitro oxidative modification. However, insulin, fibrinogen, factor VII, and lipoprotein (a) were not significantly different on the 2 diets. A postprandial study was subsequently conducted to investigate any acute effects of a tofu test meal on the oxidative modification of LDL in 16 male subjects. There was no significant difference between the susceptibility of LDL to oxidative modification before and after the tofu meal. Twenty eight healthy subjects completed a separate randomised crossover dietary intervention comparing a high MUFA fat diet, using an Australian high oleic sunflower oil, with a low fat, high carbohydrate diet on CHD risk factors. The high MUFA oil diet significantly increased high density lipoprotein cholesterol compared to the low fat diet as well as producing LDL that were more resistant to oxidative modification. Neither the size of the LDL particle nor arterial compliance were significantly different on the 2 diets. Twelve matched pairs of vegetations and omnivores were also studies to compare the habitual diet of a low and higher risk population group, to compare their risk factors and identify dietary constituents that may explain the differences. The vegetarians consumed less saturated fat (SFA) and dietary cholesterol while consuming more polyunsaturated fat, dietary fibre and vitamin E compared to omnivores. The vegetarians had lower total cholesterol, LDL cholesterol and triacylglycerol levels compared to the omnivores and had LDL particles that were more resistant to in vitro oxidation. These findings contribute to our knowledge about the dietary constituents that can alter some CHD risk factors in healthy subjects, and which could reduce the risk of developing CHD. Investigations in high risk groups might reveal even more benefits.

Includes bibliographical references. / 3 v. : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / A selection of research papers, reviews, books and book chapters ... considered representative of the works by the author over the years 1958-1993. / Thesis (D.Sc.)--University of Adelaide, Dept. of Pathology, 1995

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Abdominal obesity is a part of insulin resistance syndrome that is closely linked to increased risk of coronary artery disease (CAD). Because fat tissue acts as an endocrine target and source of hormone production, increased metabolism or production of chemical messengers in fat tissue may result in metabolic perturbations that contribute to occurrence and recurrence of coronary events. This dissertation research entails two separate approaches. The first study, a cross-sectional analysis, sought to determine whether serum cortisol responses to oral glucose loading are associated with abdominal obesity, non-esterified fatty acid (NEFA) suppression, and self-reported symptoms of depression in 26 non-diabetic coronary patients. We conclude that lower cortisol responses to oral glucose loading are associated with abdominal obesity, reduced NEFA suppression, and fewer symptoms of depression (P���0.028). Future prospective studies should determine whether psychosocial risk factors, such as depression and anxiety, increase cortisol production, whether increases in cortisol production act synergistically with a positive energy balance in the development of abdominal obesity, and whether increases in abdominal obesity lead to increases in cortisol metabolism and insulin resistance. C-reactive protein (CRP) is a marker of low-grade inflammation that is associated with increased risk for recurrent events in coronary patients. Fat tissue also secretes proinflammatory cytokines that stimulate hepatic production of CRP. Thus, the second study, an intervention study, sought to determine whether the first three months of cardiac rehabilitation could reduce serum concentrations of CRP and the proinflammatory cytokine, tumor necrosis factor-�� (TNF-��), in our non-diabetic coronary patients (N=26). Results from the intervention study showed significant reductions in serum CRP levels (P=0.012) that were associated with reductions in waist circumferences after cardiac rehabilitation (r=0.39, P=0.049). However, changes in serum TNF-�� levels after cardiac rehabilitation were nonsignificant (P=0.869). Thus, we conclude that cardiac rehabilitation may reduce the severity of low-grade inflammatory conditions, in part, through reductions in waist circumference in non-diabetic coronary patients. / Graduation date: 2001