Coronary heart disease is the leading cause of premature death in the UK. Chest pain, the most common symptoms associated with this disease, accounts for 1% of all primary care consultations, 5% of visits to emergency departments, and up to 40% of emergency admissions to hospital. When people experience acute coronary symptoms such as chest pain, or other symptoms such as pain in the arms, back or shoulder pain and pain in the jaw and neck, we know that prompt diagnosis and treatment of heart disease can significantly reduce mortality. However, we also know that when people experience these symptoms they can wait sometime before seeking medical help. Part of the problem may be that people do not attribute their symptoms a serious problem such as heart disease. Whilst several campaigns have been aimed at the general population there is no information resource targeted at people who may be at risk of heart disease to help them understand and evaluate their symptoms and take prompt action. The overall aim of this thesis is to fill this gap by producing a piloted draft information resource which aims to help people to respond effectively to symptoms that might be attributable to heart disease for people at high risk of heart disease. Using focus group discussions and individual interviews with people who had experienced symptoms that might be attributable to heart disease or might be at high risk of heart disease experiential data about their response to symptoms were gathered. Participants were also asked their views on what an information resource should be like and their experiences and views formed the basis of the content of the first draft of the information resource. In making sense of their symptom the participants drew upon a range of past experiences and the experiences of others to help them; participants who experienced severe symptoms sought help quickly; those whose symptoms were mild or transient waited, in some cases a considerable time, before seeking help. Previous personal experience may be the factor that helped those who acted quickly. Whereas the experience of others, evident in many of the accounts of those who waited, may not be sufficient to help people interpret and make sense of their own symptom experiences. The information resource incorporated the experiences of people with symptoms that ended up being attributable to heart disease and included examples of the range of symptoms that can be encountered to illustrate the different ways in which heart disease can be manifested as well as information drawn from best practice resources in the management of heart disease. Participants in the original focus group discussions and interviews were asked to be involved in the development of the resource and seventeen agreed. The information resource went through three drafts; at each stage changes were made to incorporate respondent views; at the penultimate draft health professionals’ views were also sought and used to inform the final draft which is now ready for further evaluation.

Background: Coronary heart disease (CHD) remains a major cause of death and ill- health in Scotland. Coronary artery bypass grafting (CABG) aims to relieve CHD symptoms, improve quality of life and increase life expectancy in high-risk groups. Partners may positively or negatively influence patient outcome, and they too may be adversely affected by the experience of CABG. Health care is currently organised around the patient. The partner's is seen as merely assisting patient recovery. Their health and well-being is neglected despite them being at an increased risk of CHD. Research has been limited in the partner variables that have been examined. Their health needs and concerns and the influence of the patient on partner outcome have seldom been examined and the effects of CABG on the dyad. The dyad has not previously been examined as an outcome variable of interest.

The implication of increasing consumption of functional foods, such as pulse-containing products, reveals the potential to reduce the incidence of type 2 diabetes (T2D) and coronary heart disease (CHD) and thereby achieves the cost savings associated with treatment and productivity loss. This research investigates the economic impact of such an important aspect of dietary pulse intake. The objective of the research is to determine the potential annual healthcare savings resulting from pulse flour consumption at Health Canada’s recommended daily rates. This study employs a four-step cost-of-illness approach to estimate such savings: 1) estimation of success rate of the healthy food; 2) determination of lower glycemic index, insulin concentration reduction, and lower cholesterol; 3) assumption of reduction in prevalence of T2D and CHD; 4) calculation of cost savings with regard to reduced occurrence of T2D and CHD. The findings demonstrate that annual cost savings ranging from $ 43.8 to 317.8 million (T2D category) and $ 154.9 to 958.0 million (CHD category) can be achieved for the Canada’s health budgetary framework with the increased consumption of dietary pulses. The estimations of cost savings are contingent on four scenarios: ideal, optimistic, pessimistic, and very pessimistic. People susceptible to higher blood glucose, higher insulin, and higher total cholesterol could benefit considerably by substituting pulse-containing foods for unhealthy foods. The adaptation to a dietary pattern that includes pulses will result in significant expenditure reductions in Canada’s publicly funded health care system, lessening the economic burden of illness in Canada. / October 2016

M.A. / Please refer to full text to view abstract

Student No. 0107750D M.Sc(Med) Research Report / The prescription habits of general practitioners are continually under the scrutiny of ethical critics. There are numerous factors that influence a practitioner’s decision as to which antihypertensive agents to prescribe for the treatment of hypertension. As outlined in various international and national guidelines for the management of hypertension, the recommended treatment depends on ethnicity, current life-style, diet, smoking, age, gender, family history and possible underlying or secondary conditions such as diabetes mellitus, heart failure, isolated systolic hypertension, myocardial infarction, pregnancy, and evidence of coronary artery disease (CAD), stroke or peripheral vascular disease. Currently the control of blood pressure in patients with hypertension is far from optimal with over 70% of hypertensive patients being reported as having imperfect control. A number of factors related to the patient, the practitioner or the medication may explain the high incidence of inadequate blood pressure control. One possible explanation for the poor control of blood pressure may be that practitioners fail to comply with the guidelines. Hence the aim of my study was firstly to determine whether a practitioner’s decision as to which medication to prescribe in the treatment of hypertension is influenced by the Southern African Hypertension Society Guidelines. Secondly, in an attempt to assess the validity of the results of the primary analysis, the actual prescription habits (MediCross® database) were assessed and compared to the general practitioner’s recall of their prescription habits. Questionnaires were distributed to 320 MediCross® practitioners and prescription habits were identified and substantiated by the screening of an existing MediCross® database. I chose as my sample MediCross® general practitioners, as they are demographically representative of all major urban areas in South Africa; likely to be open-minded to supporting research and answering questionnaires (as MediCross® is part of a Clinical Research Site Management Organisation); and I had access to the database of the prescriptions made by MediCross® practitioners hence enabling me to fulfil my second objective. However, it must be kept in mind that these practitioners are representative of general practitioners in urban areas only (as the title of my research report indicates). My results show that 33.1% adhere to the guidelines (when a non-conservative definition of diuretics is used); 27% have heard of the guidelines and have a copy of them. When asked to give their own opinion however, 39% thought they adhered to the guidelines. The results also show that ACE inhibitors are the most commonly prescribed drug class for uncomplicated hypertension but a comparison to a MediCross® database, of which the quality is questionable, does not support this. As the response rate to the questionnaires was only 24.7%, these results are only a pilot study; however they suggest that few general practitioners use the guidelines or even have a copy of the guidelines. This pilot study suggests that the guidelines need to be distributed more widely. Furthermore the general practitioners that responded to the questionnaire indicated that the management of hypertension is difficult in that there is no single treatment regimen appropriate for all populations and each different patient. It was also their view that clinical guidelines for the management of hypertension should more accurately reflect the uncertainty of when to initiate treatment and individual variation if they are going to take these guidelines seriously and comply with them.

Transgenic mice were generated to express a restrictive cardiomyopathy (RCM) human cardiac troponin I (cTnI) R192H mutation in the heart. My study's objective was to assess cardiac function during the development of diastolic dysfunction and to gain insight into the pathophysiological impact of the RCM cTnI mutation. Cardiac function was monitored in cTnI193His mice and wild-type littermates for a period of 12 months. It progressed gradually from abnormal relaxation to diastolic dysfunction characterized with micro- echocardiography by a reversed E/A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. The negative impact of cTnI193His on cardiac function was further demonstrated in isolated mouse working heart preparations. Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO. The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation characterized morphologically by enlarged atria and restricted ventricle and functionally by diastolic dysfunction. / by Nariman Gobara. / Thesis (M.S.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

Many cardiovascular diseases are partly due to heart muscle malfunctions. The main dynamic function in the heart is metabolism via mitochondrial respiration. And the most direct measure of oxidative tissue metabolism is the conversion rate of oxygen to water. Finding the oxygen consumption rate in the heart vessel will help us prevent the heart diseases. In the experiment, 15O-labeled RBCs (Red Blood Cells) and indocyanine green dye were injected into the isolated blood-perfused rabbit heart. The dye curves defined the inflow for the dye have the same shape as the inflow curves for the 15O oxygen. The inflow and outflow dilution curves for 15O were obtained with use of PET (Positron Emission Tomography) technology. After appropriate correction for baseline and radioactive decay, the data were transferred to a UNIX workstation for model analysis. A linear, three-region (capillary space, interstitial fluid space, and parenchymal cell space), and axially distributed model is introduced to simulate the oxygen consumption process and determine the oxygen conversion rate. Parameters of concentration are oxygen and water corresponding to capillary space, interstitial fluid space, and parenchymal cell space. The diffusion coefficients are largely independent of molecular motion. The blood flow happens only in capillary part. Other parameters are determined by experimental data. Using the input data, consumption rate is determined through a process minimizing the difference between the experimental and numerical output. Effects of key parameters on oxygen concentration and consumption rate are investigated.

A partir des données de 2 études de population menées chez des sujets âgés, non institutionnalisés, respectivement l’étude des 3 Cités et l’étude EVA (Epidémiologie du Vieillissement Artériel), nos objectifs étaient 1) de revisiter le rôle de l’athérosclérose carotidienne dans son association avec les évènements coronaires et avec les démences, en dissociant précisément l’athérome (i.e. les plaques carotidiennes ; PC) de l’hypertrophie artérielle (i.e. l’épaississement diffus de l’intima-média mesuré au niveau de l’artère carotide commune ; EIM-ACC) et 2) dans un objectif plus mécanistique, d’analyser le lien différentiel entre l’athérome, l’hypertrophie artérielle et l’un des polymorphismes nucléotidiques (rs1333049) les plus associés à la maladie coronaire et situé sur le chromosome 9 (locus 9p21).Dans un 1er travail, nous avons montré que les PC étaient associées à une augmentation du risque d’évènement coronaire à 6 ans, à l’inverse de l’EIM-ACC qui n’était pas associée au risque coronaire. De plus l’ajout des PC à un modèle comprenant les FDRCV améliorait significativement la prédiction du risque coronaire avec près de 12% des sujets correctement reclassés en terme de risque prédit (NRI = 11,7% ; IC95% = 3,1%-20,0%). Dans la seconde analyse (3C et EVA), nous avons mis en évidence une association spécifique entre les PC et le polymorphisme nucléotidique rs1333049 (OR allèle C = 1,24 ; IC 95% = 1,13-1,36). Chez les sujets de la cohorte EVA, l’allèle C était également associé à la progression des plaques carotidiennes à 4 ans, mais pas à la progression de l’EIM. Dans le dernier volet de cette thèse et de manière similaire aux évènements coronaires, il existait une association spécifiques entre les PC et la survenue de démences vasculaires/mixtes à 7 ans (HR ≥ 2 sites avec plaques vs. 0 = 1,93 ; IC 95% = 1,13-3,28). Aucune association n’était retrouvée avec l’EIM. L’ajout des plaques carotidiennes à un modèle comprenant les FDR CV et de démence permettait de reclasser correctement 43% des sujets en terme de risque de DVasc (NRI=43,0% ; IC95% = 20,2-66,2). Enfin, dans le cadre de cette thèse, nous participons à un travail collaboratif portant sur la progression individuelle de l’EIM au cours du temps en association avec la survenue d’évènements cardiovasculaires. Les données de EVA ont été intégrées à ce projet. Un premier résultat de cette méta-analyse était que la progression annuelle de l’EIM-ACC n’était associée à aucun des évènements cardiovasculaires étudiés. Au total, les résultats de cette thèse indiquent la présence d’une association différentielle des plaques carotidiennes et de l’EIM-ACC avec les évènements coronaires et les démences. Les implications sur le plan de la prévention et en termes de cibles thérapeutiques potentielles sont discutées dans cette thèse. / Using data from 2 large French cohorts of non-institutionalized older adults, namely the Three-City Study (3C) and the Vascular Aging Study (EVA), we aimed 1) to explore the respective contribution of ultrasound detected carotid plaques (e.g. atherosclerosis) and diffuse common carotid intima-media thickness (CCA-IMT) (e.g. arteriosclerosis) to incident coronary events and dementia and 2) to assess the differential relationship between carotid plaques, CCA-IMT and the coronary heart disease (CHD)-associated single polymorphism nucleotide (rs1333049) on chromosome 9p21. First, we showed that carotid plaques but not CCA-IMT were associated with an increased risk of 6-year CHD. Furthermore, carotid plaques significantly improved CHD risk prediction beyond traditional CV risk factors, as nearly 12% of the participants were correctly reclassified in terms of predicted risk(Net Reclassification Improvement (NRI) = 11.7%; 95% CI = 3.1%-20.0%). In our second analysis, including subjects from both 3C and EVA, we found a specific association between carotid plaques and the rs1333049 genotype (OR C allele at risk= 1.24; 95% CI = 1.13-1.36). Moreover, among the EVA participants, the rs1333049 genotype was also associated with carotid plaques progression over 4 years, but not with CCA-IMT progression. Thirdly, we showed a specific relationship between carotid plaques and the occurrence of 7-year vascular/mixed dementia (VaD) (HR ≥ 2 sites with plaques vs. 0 = 1.93; 95% CI = 1.13-3.28). No relationship was found for CCA-IMT. Furthermore, adding carotid plaques to a model including vascular and dementia risk factors resulted in a significant continuous NRI of 43.0% (95% CI = 20.2%-66.2%) for VaD. At last, in line with the present work, we currently participate through the EVA Study to a collaborative project on the relationship between individual IMT progression over time and cardiovascular risk. A first result recently published, showed the absence of relationship between yearly IMT progression and cardiovascular events. In summary, the present work indicates that carotid plaques and CCA-IMT are differentially associated with coronary events and vascular/mixed dementia. Potential implications of our results regarding primary prevention and therapeutic targets are discussed in this thesis.

Cardiovascular disease (CVD) consistently ranks among the leading causes of death in the United States. The most common subtype of CVD, ischemic heart disease, is a frequent precursor of myocardial infarction and heart failure, most commonly affecting the left ventricle (LV). Today, echocardiography is regarded as the gold standard in screening, diagnosis, and monitoring of LV dysfunction. But while global assessment of LV function tends to be quantitative, cardiologists with specific expertise still perform many regional evaluations subjectively. However, a more objective and quantitative measure of regional function – myocardial strain – has been developed and widely studied using 2D echocardiography. With recent developments in real-time 3D echocardiography (RT3DE), it has become possible to measure strain in its native 3D orientation as well. Our laboratory’s earlier work introduced the Optical Flow (OF) method of strain analysis, which was validated on simulated echocardiograms as well as through animal studies. The principal goal of this thesis is to translate this OF-based method of strain estimation from the research setting to the patient’s bedside. We have performed a series of studies to evaluate the feasibility, accuracy, and reproducibility of OF-based myocardial strain estimation in a routine clinical setting. The first investigation focused on the optimization of RT3DE acquisition and the OF processing pipeline for use in human subjects. Subsequently, we evaluated the capacity of this technique to distinguish abnormal strain patterns in patients with CVD and varying degrees of LV dysfunction. Our analysis revealed that segmental strain measures obtained by OF may have better sensitivity and specificity than the more commonly used global LV strains. Our third validation study examined the reproducibility of these strain measures in both healthy and diseased populations. We established that OF-based strain measures demonstrate repeatability comparable to that achieved by the latest commercial software commonly used in clinical research to estimate 2D or 3D strain. These studies were driven in large part by the absence of a ground truth or accepted gold standard of 3D strain measurements in the human LV. However, cardiac magnetic resonance imaging has had considerable success in measuring some forms of strain in the human LV. We therefore began to develop an image-processing pipeline to derive strain estimates from a new pulse sequence called 3D-DENSE. We further sought to improve the OF pipeline by automating the process of tracking the LV border. To this end, we developed a level-set based technique which tracks the LV endocardium. Our evaluation of its performance on RT3DE data confirmed that this method performs within the limits of inter-observer variability. Overall, our pilot studies of OF-based strain estimation demonstrate that the technique possesses several promising features for improving cardiologists’ ability to quantify and interpret the complex three-dimensional deformations of the human LV.

Thesis submitted to the Faculty of Arts, University of the Witwatersrand, for the degree of Doctor of Philosophy Johannesburg 1995 / The large percentage of deaths attributed to recurrent Coronary Heart Disease (CHD) has generated a search for behavioural and psychological factors which mitigate the consequences of CHD. An aim of the present thesis is to extend this search by identifying factors which predict prognosis fer recovery from CHD. Two key factors seen to influence prognosis are aerobic exercise and Type A behaviour. Extant research into the role of exercise has been hindered by methodological weaknesses. As a consequence, the precise means by which exercise influences CHD patients' psychological and physiological strain remains unclear. Similarly, the Type A literature has been flawed by the inaccurate conceptualisation and measurement of Type A behaviour as a global, and 110t a multidimensional, construct. Research which has examined the multidimensional nature of Type A behaviour has been restricted to low risk samples. Thus, a further aim. of the present research is to examine ; prognostic role of exercise and Type A components within the context of cardiac rehabilitation. In achieving this aim, three studies are conducted. [Abbreviated Abstract. Open document to view full version] / MT2017