Dietary-derived lipoproteins, chylomicrons (CM) and CM remnants (CMR), have been implicated in the progression of cardiovascular disease. Retinyl esters are currently the most widely used method for monitoring CM metabolism. The availability, however, of a specific antisera to apo B-48, the protein uniquely associated with dietary-derived lipoproteins, has allowed more extensive investigation of CM and CMR metabolism. The effect of habitual, moderate levels of exercise (3 to 4 exercise sessions a week) on the lipaemic response to meals of varying fat content was assessed in young male subjects. Apo B-48, triacylglycerol (TAG) and retinyl ester were used as markers for CM particles. Active subjects had a lower response than an inactive group in all parameters measured over time after the meals. Lipoprotein lipase (LPL) activity levels measured at the end of the postprandial period were higher in the active group. The area under the time-response curves (AUC) for apo B-48 in the inactive group increased with increasing fat content of the meals, whereas the AUC for apo B-48 was the same after each meal in the active group. Validation of a specific ELISA for apo B-48 was carried out. Cross-reactivity of the antisera with low levels of apo B-100, the protein present on endogenous lipoproteins, was ruled out. The assay was specific and sensitive for measuring apo B-48 concentrations in the CM-enriched fractions. The use of the assay in the current format for plasma samples could not be fully assessed due to difficulties with isolating a pure, concentrated sample of apo B-100 and problems with reactivity between the secondary antibody used in the assay and plasma proteins. The assay was useful for showing postprandial patterns of changes in apo B-48 levels in plasma. The effects of meal frequency on the lipaemic response to a high fat test meal challenge were assessed in an intervention study. A nibbling diet was found to cause differences between the response of various parameters after the meal (NEFA-AUC, LPL activity, infranatant-TAG AUC and time to peak) compared with the normal meal frequency. The size and density distribution of CMR in plasma were investigated. Apo B-48 was found in the IDL and LDL fractions in both the postabsorptive and postprandial states. A comparison between the retinyl ester and apo B-48 responses in the postprandial studies showed that the time to peak retinyl ester level was delayed compared to apo B-48 and TAG. The importance of apo B-48 for studying the metabolism of CM and CMR metabolism was demonstrated.

Diabetes is one of the fastest growing diseases today, affecting over a million people in the UK. Numerous medical complications, such as heart disease, are regularly associated with diabetes. Despite advances in methods of diagnosis and treatment there is still a need for greater understanding of these diseases. This will include research directed towards the influence of specific treatments and reasons for the high incidence of diabetes and heart disease in 'at risk' populations. Changes in elemental status are associated as the cause or effect of various diseased states. Elemental imbalance in diabetics can result in impaired glucose tolerance and insulin resistance and in sufferers of heart disease elemental changes impair heart rate and elasticity of blood vessels. In the UK 10,000 patients with Ischaemic Heart Disease undergo coronary artery bypass grafting (CABG) surgery each year. Elemental analysis has been carried out on blood samples collected from a group of patients admitted to hospital for bypass surgery. Proton Induced X-ray Emission (PIXE) and Instrumental Neutron Activation Analysis (INAA) have been applied as complementary analytical tools for determining elemental concentrations. Differences have been examined between CABG patients with and without diabetes. Both experimental methods have been used to investigate elemental levels in whole blood, erythrocytes and plasma. Elemental concentration varied according to the blood constituent and reflected short and long-term influences on elemental homeostasis. Plasma was found to concentrate Na, Mg and Ca the highest using both experimental techniques. All blood samples were collected and prepared at St. George's Hospital, Tooting in the UK. An additional study was conducted to investigate the influence of the bypass operation on the patient's elemental status. Whole blood was obtained at pre (1h before operation), post (1-2 hours after operation) and recovery (24 hours after completion of the operation) stages of bypass surgery. Differences between the three phases were observed, individual variations have been plotted so rates of change can be seen and evaluated with the particular medical history. Concentrations of Na, Mg, Al, P, S, Cl, K, Ca and Fe in whole blood were determined. The two measurement techniques found different concentrations however results showed a general trend that post operative concentrations were elevated compared to pre operative values. Analysis of blood drawn during the recovery phase, 24 hours after the surgery, found that concentration were typically approaching pre operative levels. Both PIXE and INAA found concentrations of Na, Mg and Al peaked post operation and then decreased in the recovery phase, towards values measured pre surgery. Various factors may be responsible for the elemental changes occurring during surgery including, hormone production, routine administration of intra-operative fluids and contact of blood with non- endothelial surfaces. Hierarchical cluster analysis has been used to confirm differences between elemental levels in pre, post and recovery stages of bypass surgery. The dendograms produced indicate significant distinction between the three stages. The explosive impact of diabetes in the UK resident Asian population is discussed and the influence of diabetogenic agents introduced. Examination of research literature revealed that betel nut has been implicated as a causative agent in several medical conditions. Samples of Betel nut and six associated chewing materials widely used in Asian communities has been collected and prepared for analysis. Instrumental neutron activation analysis has been used to determine the concentration of Na, Mg, Al, Cl, Ca, V, Mn, Cu and Br in the samples by means of short-lived radionuclides.

Coronary heart disease (CHD) has traditionally been regarded as a male disease and, because of this, the magnitude of the problem in women is often overlooked. Yet, cardiovascular disease (CVD) and CHD in particular, remains, next to cancer, the leading cause of morbidity and mortality in women. The longstanding emphasis on the problem of CHD in men, has resulted in a widespread tendency to minimise the incidence and severity of the disease in women. Moreover, most epidemiologic studies examining morbidity and mortality from CHD have focused largely on men, producing a significant gender gap in the research. The lack of information on CHD risk factors and prevention of heart disease in women in Britain is of particular concern, given that British women have one of the highest rates of coronary disease in the world. The Marks and Spencer Coronary Risk Factor Study (MSCRFS) is a cross-sectional and prospective study of CHD risk factors in female employees of the Marks and Spencer retail organisation. The present study is confined to an analysis of cross-sectional data from 14,077 women screened between June 1988 and July 1991. The prevalence and distribution of a variety of lipid, lipoprotein, biochemical, anthropometric and lifestyle-related CHD risk factors among women in the United Kingdom is described, together with their key interrelationships. In addition, the metabolic impact of exogenous hormones, specifically oral contraceptives and postmenopausal hormone replacement, is described. This study - the largest of its kind in the UK - provides reference ranges for a wide range of CHD risk factors in women in the UK, and gives a unique insight into the impact of a variety of lifestyle-related factors on CHD risk. There is an enormous potential for reducing the very high risk of CHD among women in the UK, which needs to be addressed. Based on these data, health strategies designed to reduce morbidity and mortality from CHD can be planned and implemented more effectively.

Background: Smoking continues to be the leading cause of preventable disease, disability and death in the United States attributing to more than 480,000 deaths every year. An estimated 36.5 million US adults (15% of US population) currently smoke, and more than 16 million live with a smoking-related disease. Since recent years, there has been a surge of alternate tobacco products in the US markets, and one such product that has gained importance was electronic cigarettes. Studies have demonstrated a rapid increase in e-cigarette use among US adults. However, research is limited on the effects of e-cigarette on human health. Thus, using a nationally representative sample of US adults, we investigated the association of e-cigarette use with coronary heart disease (CHD) among adults aged ≥18-years in the US. Methods: Data from the 2016 Behavioral Risk Factor Surveillance System (BRFSS) were used to conduct this study. BRFSS is a cross-sectional survey administered to 486,303 adults in all 50 states to collect information about their health-related risk behaviors, chronic health conditions and the use of preventive services. Participants’ self-reported responses were used to define study outcome (CHD), exposure (current e-cigarette use) and covariates (demographics [sex and race], behaviors [cigarette smoking, alcohol consumption, marijuana use, physical activity], and physical conditions [overweight or obesity]). Multiple logistic regression analysis was conducted to determine the association between e-cigarette use and CHD. Adjusted odds ratio and corresponding 95% confidence intervals were presented. Results: Approximately 6.19% of US adults reported CHD events and 3.1% of US adults were current e-cigarette users. Approximately 5.42% of e-cigarette smoking US adults reported CHD outcomes in 2016. Overall, the odds of CHD events was 34.9% less among e-cigarette users than those who were not e-cigarette users (adjusted odds ratio (aOR): 0.65, 95% confidence interval (CI): 0.60-0.70, p Conclusion: The study found out that e-cigarette user was less likely associated with CHD outcomes in US adults. Given the limitations of cross-sectional study nature and self-reported bias of responses, longitudinal studies with objective measures are needed to further investigate the association between e-cigarette use and CHD.

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Includes bibliographical references / Rheumatic Heart Disease (RHD) is a leading cause of heart disease in children and young adults in the developing world, with significant associated morbidity and mortality. Early secondary prophylaxis may retard the deleterious progression from its antecedent, acute rheumatic fever to permanent heart valve damage, and thus several echocardiographic screening programmes to detect asymptomatic RHD and institute early prophylaxis have been conducted. While effective interventions are available for ameliorating the effects of RHD, research on their use in different settings is scant. Key questions remain regarding the natural history of asymptomatic RHD and the optimal method for early detection. In addition, there is a lack of contemporary estimates of mortality and morbidity among the symptomatic population in the developing world. The primary purpose of the thesis was to determine the outcomes of asymptomatic and symptomatic RHD. More specifically, I sought to quantify the incidence, prevalence and outcomes of RHD in South Africa over the past two decades, determine the natural history of asymptomatic RHD and validate a focused protocol for screening in schoolchildren from Cape Town. In addition, I determined the baseline characteristics, prevalent sequelae and gaps in evidence-based implementation in children and adults from14 developing countries. Finally, I investigated the independent predictors for mortality and morbidity of RHD over a two-year period in patients from Cape Town, South Africa. My thesis has five key findings. Firstly, a systematic review of the literature showed that the incidence and prevalence of RHD over the past two decades in South Africa remains high, although there is evidence of falling cause-specific mortality at a population level. Secondly, asymptomatic RHD has a variable natural history that ranges from regression to a normal state, to persistence of disease, and progression to symptomatic RHD. Thirdly, a focused hand-held echocardiography protocol shows promising levels of sensitivity and specificity for detecting subclinical RHD. Fourthly, the baseline data from the global rheumatic heart disease registry demonstrates significant gaps in the implementation of medical and surgical interventions of proven effectiveness in low- and middle-income countries. Finally, the annual mortality rate for children and adults with RHD in Cape Town over a two-year period is 4.1%with cardiovascular events occurring at a rate of 0.18 events per patient per year. The findings encapsulated in this thesis have important implications for policy, practice and research related to the management of asymptomatic and symptomatic RHD in the world.

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No description available.

Loss of cardiac mitochondrial function with age may cause increased cardiomyocyte death through mitochondria-mediated release of apoptogenic factors. We investigated ventricular subsarcolemmal (SSM) and interfibrillar (IFM) mitochondrial bioenergetics and susceptibility towards Ca2+-induced permeability transition pore (mPTP) opening with aging and lifelong calorie restriction (CR). Cardiac mitochondria were isolated from 8-, 18-, 29- and 37-month-old male Fischer 344 × Brown Norway rats fed either ad libitum (AL) or 40% calorie restricted diets. With age, H2O2 generation did not increase and oxygen consumption did not significantly decrease in either SSM or IFM. Strikingly, IFM displayed an increased susceptibility towards mPTP opening during senescence. In contrast, Ca2+ retention capacity of SSM was not affected by age, but SSM tolerated much less Ca2+ than IFM. Only modest age-dependent increases in cytosolic caspase activities and cytochrome c levels were observed and were not affected by CR. Levels of putative mPTP-modulating components: cyclophilin-D, the adenine nucleotide translocase (ANT), and the voltage-dependent ion channel (VDAC) were not affected by aging or CR. In summary, the age-related reduction of Ca2+ retention capacity in IFM may explain the increased susceptibility to stress-induced cell death in the aged myocardium.

The purpose of this thesis was to better understand physical activity (PA) maintenance among patients who have completed cardiac rehabilitation (CR). Study 1: This study was a systematic review and meta-analysis of 19 randomized controlled trials (RCTs) testing PA and exercise maintenance interventions for adults who have completed CR. Descriptive synthesis of the studies combined with meta-analysis results provided evidence of increased PA among intervention groups compared with control groups at follow-up. Results of the meta-analysis found a significant difference in PA in the intervention groups compared to the control groups, via multiple exercise outcomes including exercise sessions/week (SMD = 0.20; 95% CI, 0.04 - 0.35), kcal/week (SMD = 0.59; 95% CI, 0.19 - 0.98), and daily steps (SMD = 2.14; 95% CI, 0.90 - 3.38). There is evidence to support the effectiveness of interventions aimed at maintaining PA and exercise among adults who have completed CR. Study 2: This study was a synthesis of qualitative studies examining factors affecting PA maintenance among individuals who have completed CR. Eight studies met the criteria for inclusion. Multiple factors were identified among participants, including self-efficacy and motivation, social support, support with the transition from supervised hospital or centre-based exercise to exercise in the community or home, perceived safety of the exercise program, and availability and accessibility of PA resources and opportunities. Examining qualitative literature suggests factors at the intrapersonal-, interpersonal-, organizational- and neighbourhood-level are important in supporting exercise maintenance after completion of CR. Results from this synthesis identified key areas for tailored program design, grounded in a social ecological approach. Study 3: This study was a secondary analysis of trial data examining predictors of participants’ moderate to vigorous physical activity (MVPA) 26 weeks after enrollment in a RCT of a PA maintenance intervention. Participants completed baseline questionnaires assessing social ecological, demographic, clinical, fitness, and behavioural variables. MVPA was assessed by accelerometer at baseline and 26 weeks later. Univariate analyses revealed nine significant baseline predictors of MVPA at 26 weeks including beliefs about exercise benefits, beliefs about exercise barriers, baseline MVPA, peak oxygen consumption, diabetes, age, sex, marital status, and work status. Multivariate analysis indicated that baseline MVPA was the only independent predictor of MVPA at 26 weeks. Given the pre-eminence of baseline MVPA, the regression analyses were re-run without baseline MVPA in the model. In that case, peak oxygen consumption became the only independent predictor of MVPA at 26 weeks. Results have implications for targeting intervention for PA maintenance in the unsupervised phase. Conclusion: The findings of this thesis provided insights into the influences on long-term PA among cardiac patients post-CR and the strategies which can support long-term PA. While there have been positive developments in understanding PA maintenance, there are important knowledge gaps that remain unaddressed. These knowledge gaps include the measurement, monitoring, and surveillance of PA behaviour and ways in which intervention research could be improved. Further research will be required to address these knowledge gaps and to build on the growing knowledge of effective PA interventions to support people with heart disease.