Dissertations / Theses on the topic 'Coronary heart disease Australia'

Objectives: Part A. To analyse existing risk-factor studies in the population of Sydney for differences in established risk factors, particularly smoking, blood pressure and blood lipids, between Southern-European-born migrants and Australian-born subjects. Part B. To examine a sample of Southern-European and Australia-born men without current CHD, of similar socio-economic background to: i. Compare factors relating to haemostasis and coagulation which have been reported as predictive of CHD risk, especially platelet aggregability, fibrinogen and Factor VIIc levels. ii. Compare other measures of haemostasis and coagulation which have been reported as varying among ethnic groups. iii. Examine the determinants of platelet aggregability, especially the nutrient content of their usual diet. iv. Examine the relations among established risk factor for CHD and measures of platelet aggregability.

As the leading cause of death and disease in Australia, Coronary Heart Disease (CHD) places a significant burden on society. There are many lifestyle factors that are known to increase the risk of CHD. This study looks at both risk factors and protective factors of CHD. Research also shows CHD prevalence to be predicted by socio-economic status (SES) variables. This study aims to identify the extent to which risk and protective factors predict CHD prevalence in an Australian National survey and whether the association between risk factors and CHD is confounded by SES variables. This study used data from the 1995 National Health Survey (NHS/1995) to evaluate known risk factors as well as the mediating effect of SES factors. Risk factors included regular cigarette smoking, physical activity and alcohol consumption. SES variables are education, income, occupation, and an index of socio-economic disadvantage based on residence. Two dependent variables for CHO used in the analysis are the first health condition reported in medical consultation and the reported use of Heart Disease I Blood Pressure (HD/BP) medications. The results indicated that ex-smokers were more likely to report CHD than those who had never smoked and those who were current smokers. Those who engaged in regular exercise were less likely to report CHD. There were no conclusive results for alcohol consumption. While income and SEIFA index, a measure of SES of residential areas, are associated with CHD prevalence, these associations are independent of the risk and protective factor associations. There is no evidence from this study that SES variables confound the effects of known risk and protective factors. The implications of these results are discussed.

[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.

Coronary heart disease (CHD) is a major health issue for immigrants in Western countries. However, little is known about cardiovascular health among Chinese immigrants, the largest non-English speaking group in Australia. This thesis aims to explore cardiovascular risk among Chinese immigrants. Firstly, the incidence of CHD and outcome after first CHD diagnosis was determined through systematic review and meta-analysis. Secondly, survey data from the 45 and Up Study examined prevalence of CHD and risk factors among Chinese immigrants compared to other Australians, and acculturation effects on their cardiovascular risk. Finally, a family-centred descriptive, qualitative study explored socio-ecological influences on Chinese immigrants’ engagement with CHD prevention. The systematic review and meta-analysis found Chinese immigrants in Western countries had lower CHD incidence compared with Whites (OR=0.29; P<0.001), yet had higher short-term mortality after CHD events compared with Whites (OR=1.34; P<0.05). The 45 and Up Study data showed higher prevalence of cardiovascular risk factors among Chinese Australians, including higher prevalence of current smoking, physical inactivity and diabetes and worse cardiovascular risk profiles. Those who migrated as either a child or adolescent were particularly at risk for diabetes and overweight/obesity. The qualitative findings identified important barriers and facilitators for effective CHD prevention and care among Chinese immigrants. Barriers included individual factors such as health knowledge deficits, widespread non-adherence to primary prevention medication and low English proficiency. The cardiovascular health of Chinese immigrants is influenced by complex individual, environmental and contextual exposure during their life course, both in their country of origin and in their new country. This thesis identifies important gaps in CHD prevention and calls for culturally-specific preventive programs.

Coronary heart disease (CHD) is the single largest cause of death in Australia. Lack of physical activity is a primary risk factor for CHD. The thesis aimed to quantify the efficacy of walking in reducing CHD risk. Meta-analyses were performed for the quantification with the application of random-effect meta-regression models. The thesis also aimed to quantify reductions in CHD-related direct healthcare costs, productivity loss and disease burden resulting from walking interventions in Australia, using the population attributable fraction model, the work and leisure models, and the consumer surplus model. Economic evaluations were also conducted to estimate CHD-related productivity loss using the human capital and the friction methods. The results indicated that 30 minutes of normal walking a day for 5-7 days a week compared to physical inactivity reduced CHD risk by 24%. There existed a dose-response relationship between walking and CHD risk reduction. An increment of approximately 30 minutes of normal walking a day for 5 days a week reduced CHD risk by 19%. The annual productivity loss resulting from CHD was estimated at AU$1.79 billion based on the human capital method and AU$25.05 million under the friction method. 30 minutes of normal walking a day for 5-7 days a week by the country???s ???sufficient??? walking population was shown to generate an estimated $126.73 million in net direct healthcare savings annually. The net economic savings could increase to AU$419.9 million if the whole inactive population engaged in ???sufficient??? walking. The study also found that 30 minutes of normal walking a day for 5-7 days a week reduced the burden of CHD by an estimated 25,065 DALYs and the productivity loss by AU$162.65 million annually under the leisure model. If the whole inactive population engaged in such walking, the total disease burden and productivity loss could be reduced by approximately one third. The findings present epidemiological and economic evidence in support of the national physical activity guidelines, which encourage the general public to engage in moderate physical activity including walking for a minimum of 30 minutes a day for 5-7 days a week.

Background: A series of population-based studies across the world over the last half century have confirmed that retinal microvascular signs can predict clinical coronary heart disease. There is also increasing recognition that coronary microvascular dysfunction may play a role in coronary heart disease. Existing studies, however, lack a substantial proportion of individuals with coronary artery disease (CAD) within their respective study samples, and rarely assess CAD using objective indices of disease extent and severity as quantified by coronary angiography. Extant literature also focuses more on the role of retinopathy and retinal vessel calibre, whereas this thesis also turns its attention to methods of quantifying the retinal vascular architecture using newer retinal vessel geometric measures like Df, curvature tortuosity, and branching angle. The rationale for the use of these retinal vessel geometric measures is that they add to the growing array of non-invasive research tools to probe the microcirculation. In this way, they serve as an excellent surrogate for the systemic microcirculation, and could even be used as a prediction tool for cardiovascular disease.1 There is growing interest in the means by which coronary microvascular dysfunction play a role in cardiovascular disease, particularly in women. People with symptoms of acute coronary syndrome who undergo coronary catheterisation and angiography but are found to have minimal quantitative evidence for CAD (cardiac syndrome X) also pose a diagnostic dilemma. This group has been assumed to have coronary microvascular dysfunction, but confirming this diagnosis has been difficult due to the lack of non-invasive modalities to image the coronary microcirculation. The retina provides exactly such a means of visualising the microcirculation, affording an in vivo window into the structure and function of the human circulation and its role in cardiovascular disease pathology. Thus, this thesis attempts to explore this unique link between retinal pathology with CAD and other cardiovascular disease, as well as to examine the association between common ocular conditions and CAD. Objectives: (i) To determine the prevalence of retinal vessel measures (retinal arteriolar narrowing and venular widening), as well as common ocular conditions, in a unique clinical sample of patients with or at high risk of CAD; (ii) to assess the associations between CAD, metabolic syndrome, and hypertension with retinal microvascular signs/ocular conditions — including retinal vessel measures, age-related macular degeneration (AMD), epiretinal membrane (ERM), and cataract. The end goal was to identify new modifiable risk factors for CAD and other systemic vascular disease, as well as retinal and other ocular pathology. Methods: The Australian Heart Eye Study (AHES) is a cross-sectional observational study that surveyed 1680 participants who presented to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. The objective of the study was to evaluate the associations of retinal microvascular signs with angiographically confirmed CAD. The candidate received training in Singapore in order to utilise a semi-automated computer-assisted program developed by the National University of Singapore and Singapore Eye Research Institute known as Singapore ‘I’ Vessel Assessment (SIVA version 1.0) to quantitatively assess a range of retinal vascular geometric measures from digital fundus photographs. With the assistance of another trained grader, the candidate graded the AHES photographs using SIVA by following a standardised protocol, masked to patient characteristics.2, 3 Fractal dimension (Df) was calculated from skeletonised line tracings using a box-counting method, which divided each photograph into a series of squares of various side lengths.4 Df was defined as the gradient of logarithms of the number of boxes and the size of those boxes.5, 6 The more complex the branching pattern, the greater the Df. Curvature tortuosity was derived from the integral of the curvature square along the path of the vessel, normalised by the total path length.7 This took into account bowing and points of inflection,8 in contrast with simple tortuosity, which fails to distinguish between increased length due to bowing and that due to multiple points of inflection.9 The straighter the vessel, the lower the tortuosity value.8 Retinal arteriolar tortuosity and retinal venular tortuosity were thus a measure of the average tortuosity of the arterioles and venules in the eye, respectively. Retinal vascular branching angle was defined as the first angle subtended between two daughter vessels at each vascular bifurcation.8, 10 Retinal arteriolar branching angle and retinal venular branching angle quantify the average branching angles of arterioles and venules of the eye, respectively.4 Retinal vessel calibre measures were also obtained using retinal grading software.11, 12 Average retinal arteriolar and venular calibres were calculated using the Knudtson-Hubbard formula and presented as central retinal arteriolar equivalent (CRAE) or central venular equivalent (CRVE), respectively.13 A combined retinal score was constructed to attempt to reflect the joint effect of multiple retinal vessel parameters on CAD using those variables that were most strongly significant in multivariate analysis — Df, arteriolar curvature tortuosity, and retinal arteriolar calibre. Each of these variables were considered in binary terms (above or below the median), giving a total of eight possible combinations of these variables. Those combinations with all three variables above their respective medians were assigned a combined retinal score of 0, while those combinations with all three variables below their respective medians were assigned a combined score of 2. All other combinations were assigned a score of 1. AMD is the leading cause of blindness and low vision in older adults.14 The presence of early and late AMD was determined using the Wisconsin AMD Grading System.15 Early AMD prevalence was defined as the absence of late AMD and presence of either (i) large (0.125 mm diameter) indistinct soft or reticular drusen, or (ii) both large distinct soft drusen and retinal pigmentary abnormalities (hyperpigmentation or hypopigmentation). Similarly, late AMD prevalence was defined as the presence of either neovascular or atrophic AMD in that eye. Neovascular AMD was defined as presence of serous or haemorrhagic detachment of the retinal pigment epithelium (RPE) or sensory retina, presence of subretinal or sub-RPE haemorrhage, or subretinal fibrosis. Atrophic AMD was defined as a discrete area, at least 175 µm in diameter, of retinal depigmentation characterised by a sharp border and presence of visible choroidal vessels.16 “Any AMD” prevalence was defined as the presence of either early or late AMD.17 The classification and grading system for ERM was the same as in the baseline Blue Mountains Eye Study (BMES-1),18 adopted from Klein et al.19 Two types of ERMs were identified: a more severe form, termed preretinal macular fibrosis (PMF), in which superficial retinal folds and traction lines were identified; and a less severe form termed cellophane macular reflex (CMR), without visible retinal folds. Eyes with both CMR and PMF present were classified as having PMF. As quantitative data on cataract was not available from the AHES, cataract surgery prevalence, as obtained from a detailed questionnaire, was used instead as a marker variable for cataract. CAD was quantified using objective scoring systems based on the severity and extent of coronary artery stenosis, as assessed from coronary angiography. The coronary artery segments were defined using the Syntax system, which divides the arterial tree into 16 segments, based on the modified American Heart Association (AHA) classification.20 For each segment, the severity of obstruction was documented using several grades: normal, 1-25%, 25-50%, 50-74%, 75-99% and 100% (occluded). Each lesion that was visually scored as greater than 50% luminal obstruction in a vessel that was ≥1.5mm diameter was further analysed using quantitative coronary analysis (QCA). The specific parameter used to quantify CAD are described in further detail in the Methodology chapter (2.1). Metabolic syndrome was defined as per the Third Report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel,26 please see Chapter 2.1 for further details. Results: Retinal vessel calibre Persons with metabolic syndrome (compared to without) had narrower retinal arteriolar calibre in multivariate analysis (mean difference 4.3 µm, p<0.0001). Similarly, those with hypertension (compared to without) had narrower retinal arteriolar calibre in multivariate analysis (mean arteriolar calibre difference 2.1 µm, p=0.02). This association was present among persons both with and without CAD (mean difference 5.0 µm, p=0.04). Stratification by sex indicated that women with hypertension had narrower retinal arterioles compared to normotensive women (multivariable-adjusted p=0.04). Retinal vascular geometric measures Retinal vascular Df and curvature tortuosity decreased with increasing age; women had significantly lower Df than men (p<0.003). Straighter retinal vessels were associated with CAD extent and Gensini scores in multivariate analysis (p<0.02). In sex-stratified multivariate analysis, straighter arterioles and narrower venular branching angles were associated with greater odds of overall CAD in men, while straighter venules were associated with CAD in women. Accounting for media opacity by sub-group analysis in pseudophakic patients, the combined retinal score was associated with stenosis greater than 50% in any coronary artery segment (vessel score) and obstructive coronary stenosis in all three main coronary arteries (segment score) (p=0.01). Lower Df and narrower arteriolar branching angle were associated with CAD vessel score (p<0.03). Other ocular conditions Prevalence of early and late AMD was 5.8% (n = 86) and 1.4% (n = 21), respectively. After multivariable adjustment, patients with obstructive coronary stenosis in all three main coronary arteries (segment score) had almost three-fold higher likelihood of early AMD, OR 2.67 (95% CI 1.24-5.78). CAD was not associated with late AMD. There were no significant associations between ERM or cataract surgery with CAD. However, prevalence of severe ERM — PMF — was significantly higher than the corresponding age-standardised prevalence in the BMES-1 (p<0.001). Overall prevalence of ERM was 7.0% (n = 115), with that of CMR and PMF each being 3.5%. Prevalence of cataract surgery was 13.1% (n = 218) in the AHES, with a mean age of 67.1 years. The prevalence of cataract surgery in this clinic-based cohort was significantly greater (p<0.0001) and the mean age was significantly lower (p≤0.0005) than that of the population-based cohort, the BMES-1. Conclusion: This thesis represents the largest clinic-based cohort that examined the associations between quantitatively-assessed CAD with and without coronary artery stenosis, and a wide spectrum of retinal microvascular signs and ocular diseases. These include retinal arteriolar narrowing, venular widening, Df, curvature tortuosity, branching angle, AMD, ERM, and cataract. No studies have as yet examined the relationship of retinal microvascular signs specifically to the presence, absence, extent, or severity of angiographically-assessed CAD. This data will assist in determining how we may infer retinal microvascular signs from differences in coronary vasculopathy. With regards to retinal vessel calibre, the candidate found that metabolic syndrome was independently associated with narrower retinal arterioles among those at high risk of CAD. As well, hypertension was independently associated with narrower retinal arterioles in those with and without CAD, both confirming and augmenting extant literature on this subject. In terms of retinal vascular geometric measures, this thesis provided some evidence to suggest that Df and curvature tortuosity are associated with CAD extent and severity, after accounting for the impact of media opacity. A sparser retinal microvascular network (smaller Df) was associated with older age and female sex. In regards to key ocular diseases in the AHES, severity of coronary stenosis and the presence of stenotic lesions were independently associated with AMD, specifically early AMD, in our cohort of patients presenting for coronary angiography to Westmead Hospital. While cardiovascular disease (specifically severity and extent of CAD) was not associated with ERM, this thesis presents evidence to suggest that there may be a greater prevalence of severe ERM (PMF) in a high cardiovascular risk cohort (specifically, the AHES), relative to population-based studies. This thesis also proposes that patients with cardiovascular risk factors have significantly younger age of onset and greater prevalence of cataract surgery than that of the general population, although severity and extent of CAD was not shown to be associated with prevalent cataract surgery. Overall, the findings of this thesis establish independent links between cardiovascular and ophthalmic pathology, that is, between macrovascular disease such as CAD, and both retinal vessel calibre and newer retinal vascular geometric microvascular signs. These findings help strengthen the ongoing hypothesis that non-invasive retinal and other ophthalmic imaging could be a useful adjunct to coronary angiography and other more conventional means of assessing cardiovascular disease.

Coronary heart disease (CHD) is the major cause of morbidity and mortality globally. While primary and secondary prevention programmes indisputably reduce the burden of CHD and increase quality of life, they are often underused, particularly by women and ethnic minorities. Lower referral rate, inaccessibility of services, being female, lack of support, insufficient income, impaired health literacy, inappropriateness of the programmes and the failure of health care organisations and programmes to provide culturally competent care to diverse racial, ethnic and cultural groups are some contributing factors. The use of health care services also appears to be influenced by perceived vulnerability to CHD. An individual’s subjective judgment about the characteristics and severity of a risk, that is the perception of risk, and causal attributions play an important role in responding to risk. Attitudes towards CHD risk and the associated risk factors such as smoking, diet, physical activity and obesity are mainly underpinned within cultural beliefs and practices. The value placed on adopting favourable health seeking behaviours, and a willingness to comply with medical advice are also often related to cultural beliefs, values and experiences. There is, therefore, a need to explore CHD risk perception in culturally diverse populations. Understanding these risks can help health practitioners tailor health messages and services more effectively to facilitate behaviour change in target groups, which is critical in the management of CHD. This thesis aimed to explore the relationship between Middle Eastern women’s perceived and estimated absolute risk of CHD to inform primary and secondary prevention programmes. This thesis comprised two discrete, yet interrelated studies and employed a mixed method to elicit the participants’ perception of general and personal CHD risk. Focus groups were used to capture the collective views of migrant Turkish, Persian and Arab Middle Eastern women about their perceptions of the risk of developing CHD, causal attributions and risk reducing behaviours. The three main themes that emerged from the focus group discussions were: (a) Middle Eastern women underestimated the risk of CHD; (b) stress is a pervasive factor in the lives of Middle Eastern women; and (c) Middle Eastern women face many barriers to reduce their risk of CHD. Participants’ biological, behavioural and socio-economical risk factors showed that the study participants were at increased CHD risk due to high prevalence of some risk factors such as high blood cholesterol level, obesity, inactivity and psychological distress. Yet, the participants underestimated their personal CHD risk and perceived themselves to be at increased risk of psychological disorders such as depression. Further, those who perceived some level of increased CHD risk attributed it more to their psychological status rather than life style factors. Underestimation of the risk, inaccurate causal attributions, low socio-economic status and low health literacy accompanied with lack of culturally and linguistically competent programmes to assist women in protecting their cardiovascular health are some identified barriers to CHD risk reducing behaviours among Middle Eastern women. Findings of this study have significant implications for cardiac rehabilitation services to develop culturally and linguistically competent programmes to communicate Middle Eastern women while taking into account cultural differences in beliefs and traditions, socioeconomic status and health literacy. These differences should be considered in CR design, implementation and evaluation.

Using mean telomere length as a marker of biological age, I show that: 1. Subjects with premature myocardial infarction (MI) have significantly shorter telomeres than age-sex matched, healthy, controls. The mean telomere length in MI subjects was similar to controls almost 11 years older. 2. Healthy young adult children of families with a strong history of premature MI have shorter telomeres than age matched children of families without such a history. 3. Shorter telomere lengths are associated with increase risk of subsequent CHD events in a prospective study. This analysis was carried out on samples collected in the West of Scotland Coronary Prevention Study (WOSCOPS). This randomised blinded trial was designated to examine the benefits of statin treatment on preventing CHD and showed a 30% reduction of events in those treated with pravastatin. Interestingly, my analysis showed that this benefit of statin is only seen in those subjects at higher risk of CHD based on their telomere length.;As the final part of the thesis I carried out a quantitative linkage trait (QTL) analysis in sib-pairs in an attempt to identify genetic loci regulating telomere length. I report the mapping of a major QTL on chromosome 12 that determines almost 50% of the inter-individual variation in mean telomere length.;These findings support a novel "telomere" hypothesis of CHD. They indicate that telomere biology is intimately linked to the genetic aetiology and pathogenesis of CHD. Specifically, the findings suggest that (i) those individuals born with shorter telomeres may be at increased risk of CHD (ii) rather than individual genes, a more global structural property of the genetic material may explain the familial basis of CHD (iii) variation in telomere length may explain, in part, the variable age of onset of CHD. The findings provide several new avenues for future research.

Fifty percent of the diagnosed cases of coronary heart disease in the United States are of unknown etiology. This study proposed that five personality traits— achievement, dominance, aggression, succorance and Critical Parent—differentiate individuals with coronary heart disease manifestations. The ultimate goal of this research was to formulate a predictive profile of at-risk individuals of developing coronary heart disease. Cardiac rehabilitation units' participants from across the United States were recruited as subjects. Randomly selected cardiac rehabilitation units were sent an initial letter inquiring whether their staff would be willing to participate in the study by administering the instruments to their participants. Eight units from each of the 50 states were contacted. A total of fourteen units agreed to participate. One hundred sixty-nine subjects completed the Demographic Data Questionnaire and the Adjective Check List. Five scale scores, representing the five personality differentials, were analyzed. Comparison of the male subject population (n=135) and the male normative population (n=198) revealed no significant differences in terms of the five traits. Comparison of diagnostic subgroups of the subject population also revealed no significant differences. It was concluded that the subject population did not differ significantly from the normative population in terms of the five traits assess by the instrument used. The goal of a predictive profile was not realized due to this lack of findings.
Master of Science
incomplete_metadata

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.
Includes bibliographical references (leaves 69-71).
Heart rate variability (HRV), the beat-to-beat fluctuation of the heart rate, is a non-invasive test that measures the autonomic regulation of the heart. Assessment of HRV has been shown to predict the risk of mortality in patients after an acute myocardial infarction. Recently, the Krieger lab at MIT developed genetically engineered double knockout (dKO) mice that develop coronary artery disease accompanied by spontaneous myocardial infarctions and die at a very young age. This thesis investigated whether HRV could function as a prognostic indicator in the dKO mouse. A novel method for estimating physiological state of the mouse from the electrocardiogram using an innovative activity index was developed in order to compare HRV variables at different times while controlling for physiologic state. Traditional time and frequency domain variables were used to assess the prognostic power of HRV. Results have shown that none of the HRV variables were helpful in predicting mortality in the dKO mice. Mean heart rate showed some prognostic power, but it was not consistent in all the dKO mice. Finally, the activity index developed in this thesis provided a reliable metric for activity in mice as validated by a camera with motion detection.
by Laurence Zapanta.
S.M.

Coronary heart disease (CHD) is the result of the accumulation of atheromatous plaques within the walls of the arteries that supply the myocardium with oxygen and nutrients. The WHO estimated that in 2002, 12.6% of deaths worldwide were from CHD. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/33551

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.

Objective: To examine the effect of exercise-based cardiac rehabilitation program for secondary prevention of coronary heart disease on cardiac-related mortality, recurrent cardiovascular event and quality of life. Methods: All studies published between 1990 and 2013 in PubMed, and from 1980 to 2013 in EMBASE, which evaluated the effectiveness of exercise-based cardiac rehabilitation program for coronary heart disease. Using the specific keywords “Cardiac rehabilitation”, “Coronary heart disease” OR “Ischemic heart disease” [MeSH], “Exercise” OR “Physical activities” AND “Quality of life” OR “Mortality” AND Cardiovascular events” were searched. A total of 7randomized controlled trials out of 5,051articles from PubMed and 117 articles from EMBASE were included in this systematic review. The primary outcome measures used in the included seven studies were HRQOL, restenosis, cardiac event, cardiac related mortality. Similar demographic and clinical characteristics of the subjects between the intervention and the control groups were recorded. The studies were from five countries. The average age of the subjects in the seven studies was 61years, the average half of them have history of myocardial infarction. Though there were discrepancies among the results generated in the included studies, the potential benefits of exercise-based cardiac rehabilitation could be seen. Results: Compared with the non-exercise-based cardiac rehabilitation, patients allocated to the exercise-based cardiac rehabilitation program had greater improvement in HRQOL and reduction of cardiac events. The result of reducing restenosis was inconsistent. The cardiac related mortality is not significant difference between exercise-based and non-exercise-based cardiac rehabilitation.
published_or_final_version
Public Health
Master
Master of Public Health

In countries where people of South Asian origin have settled, unexpectedly high coronary heart disease rates have been recorded in South Asian men and women compared with other ethnic groups. In England high CHD mortality is shared by Gujarati Hindus, Punjabi Sikhs and Muslims from Pakistan and Bangladesh. The high CHD rates in these populations are unexplained by levels of smoking, blood pressure, plasma cholesterol or dietary fat intake. To test whether disturbances of haemostatic activity, lipoprotein metabolism or carbohydrate metabolism might underlie the high CHD mortality in South Asians, a population study in east London was undertaken. The results confirmed that the high CHD rates in South Asians compared with the native British population cannot be explained by differences in the distributions of blood pressure or plasma cholesterol. The hypothesis of a disturbance of haemostatic activity was not supported. A pattern of low plasma HDL cholesterol and high triglyceride levels, high serum insulin levels after a glucose load and high prevalence of non-insulin-dependent diabetes was identified in CD Bangladeshis. On the basis of these findings and a review of other recent work it is suggested that: (i) insulin resistance underlies these disturbances of lipoprotein and carbohydrate metabolism in Bangladeshis; (ii) this tendency to insulin resistance is a general pattern in South Asian populations overseas; and (iii) it is a possible underlying mechanism for the high rates of both CHD and diabetes in these populations. The planning of a large study to test this is described. Preliminary results confirm that a syndrome of metabolic disturbances related to insulin resistance, first identified in Bangladeshis, is present also in Gujaratis and Punjabis. This is associated with a striking tendency to central obesity in South Asians. These findings point to the aetiological role of insulin resistance in CHD and suggest possible strategies for prevention in South Asian communities.

Psychosocial factors are thought to contribute to the long term development of coronary artery disease (CAD), to the triggering of cardiac events in people with advanced disease, and to adaptation following acute coronary syndromes (ACS). My thesis presents three studies addressing different aspects of the relationship between emotional factors and CAD, using different methodologies. They focus on the role of negative emotions in vulnerability to myocardial ischaemia in daily life, the influence of acute emotional triggers of ACS on long term quality of life, and the effect of depression following ACS on a particularly important aspect of adaptation, namely return to work. The first study, called the Silent Ischaemia Study (SIS) investigated 88 out-patients with suspected CAD who underwent 24 hour ambulatory electrocardiogram (ECG) monitoring, together with saliva sampling and characterisation of daily life by a new method called the Day Reconstruction Method (DRM). The results indicated that in patients with definite CAD, depressed mood was associated with reduced high frequency and increased low frequency heart rate variability (HRV), suggestive of parasympathetic withdrawal. The Cortisol slope over the day was flatter in more depressed patients with CAD. Episodes of transient ischaemia and/or arrhythmia were also associated with increased negative affect, but their incidence was low, primarily because most patients were medicated with beta blockers. The second and third studies derive from the ACCENT (Acute Coronary Syndrome, Emotion and Triggers) study, exploring long term adaptation following ACS. Analyses showed that the likelihood of returning to work was negatively associated with depression immediately following ACS, independently of clinical and demographic factors, and that emotional triggers predicted elevated anxiety and poor mental health status at 12 and 36 months independently of covariates. In combination, these studies suggest that negative emotional status contribute both to the onset of acute cardiac events, and to adaptation following ACS.

This thesis describes the characterisation and development of covalently immobilised recombinant human tropoelastin (TE) on a plasma-activated coating (PAC) as a potential stent coating for the treatment of coronary artery disease. A biomimetic approach was used to create a biocompatible coating with an immobilised human protein to enhance biointegration of an implanted stent. A coating that enhanced endothelialisation while displaying low tbrombogenicity was developed and characterised in vitro and in vivo. Covalent binding of TE to PAC was verified using ELISA and radiolabelled TE. Modulating the gas composition of the PAC, and therefore its mechanical and biological properties, resulted in varying amounts of covalently bound TE. The nitrogen containing PA Cs covalently bound up to 89± 1 % of physisorbed TE. The N2/Ar PAC covalently bound a monolayer of TE and was chosen for further characterisation. The covalent binding capacity of PAC extended for at least a year, retaining 65±1 % of its covalent TE binding capacity. Restoration of the full covalent binding capacity was achieved upon heat treatment of the PAC. TE was shown to support the attachment and proliferation of endothelial cells (ECs) when physisorbed to tissue culture plastic (TCP). This was comparable to other adhesive extracellular matrix proteins, fibronectin and collagen. The morphology and distribution of ECs cultured on 316L SS, PAC and PAC+TE was investigated using reflective, fluorescence and scanning electron microscopy. PAC+TE supported increased endothelial attachment and proliferation compared to uncoated 3 l 6L SS and PAC. An EC phenotype was confirmed on 316L SS, PAC and PAC+TE by immunofluorescent labelling of endothelial cell specific markers, CD3 I and vWF. As the thrombogenicity of blood contacting medical devices is crucial, methodology was developed to test the haemocompatibility of metallic surfaces in vitro. In static adhesion assays using whole heparinised blood, PAC was found to confer low thrombogenicity compared to 3 l 6L SS, and nitrogen again modulated this property. PAC and PAC+TE showed lower thrombogenicity than 316L SS after 60 min incubation. A modified Chandler loop was developed to test the tbrombogenicity of metallic surfaces in the presence of flowing blood. PAC and PAC+TE were again found to display low thrombogenicity, resulting in a 3-fold increase in the time to thrombus formation compared to 3 I 6L SS. This effect correlated with a 65±1 % increase in soluble P-selectin, a platelet activation marker on 3 l 6L SS. No significant platelet activation occurred on PAC or PAC+TE. The low thrombogenicity of PAC was retained for between 3 and 7 months. Furthermore, TE coated 3 I 6L SS displayed lower thrombogenicity than uncoated 316L SS, or fibronectin-or collagen-coated 316L SS. The PAC was translated to a 316L SS laser cut stent for evaluation and in vivo testing. The PAC deposition was altered to coat all surfaces and resisted delamination. In vitro crimping and expansion of the PAC stent showed only the formation of nanocracks, compared to the large scale delamination observed on a commercially available Taxus Liberte stent. The covalent TE binding capacity and non-thrombogenicity of the PAC were maintained on the stent PAC. The endothelialisation of PAC and PAC+TE stents was evaluated in vivo. This study marks the first comparator analysis of bare metal stents (BMS), PAC and PAC+ TE stents in a well-characterised model of rabbit bilateral iliac stenting. PAC and PAC+ TE stents were well tolerated and showed no gross inflammatory response. Cell coverage of stent struts occurred by 7 days post-implantation with endotheJialisation occurring both between the struts and over the struts in all samples. PAC and PAC+ TE showed no difference in the rate of endothelialisation compared to BMS, the standard corrunerciaJly available stents. In further work, covalently immobilised TE was found to be susceptible to proteolytic cleavage by the common blood plasma proteases kallikrein and thrombin, which predominantly cleave TE at its arginine 515 residue. A mutant form of TE, R5 I 5A was shown to resist proteolytic cleavage at the 515 residue and thus retained the C-terminus of the protein which is required for cell attachment. This mutant form of TE retained the equivalent level of covalent binding to PAC and would therefore be a suitable candidate for application to a PAC stent for in vivo evaluation.