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Background: The preventable risk factors for cardiovascular diseases (CVD) and diabetes cluster together and can be tracked from childhood into adulthood. There is evidence that sleep, cardiorespiratory fitness and socioeconomic status (SES) are related to the component risk factors of cardiometabolic syndrome, but this is mainly in adults. Current interventions to prevent cardiometabolic syndrome, also, are not robust enough and multisectoral approaches are still lacking in preventing these preventable risk factors. The aim of this thesis is to evaluate prevalence, identify some of the causes of these risk factors, their social determinants and how they are associated with another in English schoolchildren. Setting: Field·based research including schoolchildren from the East of England, United Kingdom. Methods: Cross~section of English state schoolchildren between lO~16 years participating in the East of England Healthy Hearts study. Height, weight and blood pressure (BP) measured by stadiometer, weighing scales and automated BP monitors using standard procedures respectively. Cardiorespiratory fitness assessed by the 20m shuttle~run test. Demographic data, screen time, sleep & wake time and physical activity (P A) levels were measured using questionnaires. Schoolchildren level of deprivation was measured using English Index of Multiple Deprivation. Metabolic risk profiles were categorised based on weight status and SBP status. Findings: Overall, 36% of schoolchildren were exposed to over 2 hours of daily screen time. Those reportiIlg <2h daily screen time were more likely to be active than 1 • . those reporting 2-4 h (OR 1.51, 95%CI 1.26-1.82) or >4h (OR 2.26, 95%CI 1.91 - 2.67). Prevalence of elevated mean arterial pressure (MPJl) was 14.8% overall but rose to 35.7% in those who were both obese and unfit. When compared with schoolchildren engaging in PA daily with adults in their household, schoolchildren who have reported no PA daily with adults in their household were likely (OR 1.54, 95%CI 1.07-2.20) to have an elevated MR profile. Rural children were more active than those from urban areas, but this was not evident when a trilateral division was used. About 40% of schoolchildren go to bed late at night. Late bedtime was associated with deprivation in schoolchildren. Compared to those with <2hours of daily screen time, the odds ratios for late bedtimes were higher in schoolchildren who spend 2-4 hours on screen time (OR 1.50, 95%CI 1.07- 2.09) and highest in those with> 4 hours of daily screen time (OR 1.97, 95%CI 1.34-2.89). Interpretations: Sedentary behaviour, parental influences, cardiorespiratory fitness, place and location of habitation are associated with the causes of CVD and component factors of cardiometabolic syndrome in schoolchildren. There was a high prevalence of>2h daily screen time in English schoolchildren. PA is lower in children reporting 2-4h versus <2h daily screen time and lower still in those classified'as heavy users (>4h) independent of deprivation, Increasing cardiorespiratory fitness level may have a positive impact on the weight-related elevations of MAP seen in obese and overweight schoolchildren. Joint PA with an adult within household could increase schoolchildren's cardiorespiratory fitness level, PA level and may reduce the risk of metabolic diseases. Rural environments support PA in children but not PA of adole scents, Town and fringe areas with mixed elements of rural and urban land use appear to fac ilitate and sustain PA in both children and adolescents, High screen time 2 , j and deprivation may explain lateness in bedtime in English schoolchildren. Family centred interventions may be important to reduce screen time and improve metabolic profile .

It is well documented that British South Asians (BSAs; people of South Asian origin residing in the UK) experience an elevated risk of developing coronary heart disease. The disease rate is approximately 50% higher than the national average. Many causal factors for this unfavourable risk profile have been put forward indicating that it is likely to be explained by a complex interplay of both genetic and lifestyle factors. Components of the BSA diet coupled with an inactive lifestyle have been identified as modifiable risk factors which could play a significant role in the prevention of this disease. Despite the identification of modifiable risk factors, health promotion interventions with measurable behavioural outcomes designed for this population are sparse. The testing of prevention strategies amongst this population is of vital importance. This thesis aimed to address the current gap in the literature by designing and testing a novel health promotion intervention specifically for the younger BSA population by means of a randomised controlled trial. The intervention was informed and underpinned by two prominent theories in the field of health research - prospect theory and the theory of planned behaviour. A novel variable, cultural sensitivity, was also manipulated. The intervention aimed to target change in two behaviours - the reduction of overall fat and an increase in physical activity. The intervention was informed and designed using the findings of a .systernatic review of the message framing literature (Chapter 2), a qualitative study which aimed to identify the barriers and facilitators to healthy living for BSAs (Chapter 3) and by the design and piloting of theory-driven behaviour change DVDs (Chapter 4). The findings of the research showed that the effects of message framing and cultural sensitivity are different for a) the type of behaviour being promoted (dietary vs. physical activity) and b) BSA males and females. It appears that BSA males and females respond differently to health promotion information relating to physical activity, yet no gender differences were apparent for dietary behaviours. These findings suggest that BSA males and females may require tailored approaches for health behaviour change interventions and there was evidence to suggest that there may be some utility in manipulating health information, both in terms of framing and cultural sensitivity, for the BSA audience. The findings did not provide any support for the mediating role of social cognitive variables on health behaviour change.

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in many developing and developed countries. This dissertation proposes a framework for gaining a greater understanding of the inflammatory process that is thought to result in the development of atherosclerosis and effects of radiation on the subsequent cardiovascular disease through statistical analysis and mathematical modelling of this process. The potential effect of low dose radiation in atherosclerotic initiation and progression is assessed utilising data on inflammatory markers and plaque development generated by European and Canadian researchers collected as part of the EU NOTE Project. Following suggestions from previous in vitro and in vivo experimental data, the hypothesis under consideration is that at low doses and dose rates there is a largely antiinflammatory response. Implications of this for induction of atherosclerosis after low dose and low dose-rate exposure are assessed. Two and three dimensional reaction-diffusion models of the cardiovascular system are constructed. These are used to assess perturbations of equilibrium and non-equilibrium states. Inferences for low dose mechanisms in the light of much biological and epidemiological data are considered. Chapter 1 serves as an introduction, describing the aetiology of atherosclerosis, a complex disease with many routes to initiation and progression, as well as environmental, biochemical, genetic and mechanical risk factors. This chapter surveys the extensive literature on the subject. Effects of radiation and mechanisms of cardiovascular injury are likewise assessed and the findings from various epidemiological and animal studies along with statistical considerations are discussed. Chapter 2 gives an overview of mathematical models of cardiovascular disease, and how they may illuminate the structure and evolution of CVD from various perspectives; this chapter outlines challenges in using mathematics as a tool for analysing this complex process. Chapter 3 proposes a spatial reaction diffusion model for atherosclerosis and provides a general framework for modelling early stage disease. Numerical implementation of the equations is performed based on parameter values derived from the biological and epidemiological literature. Chapter 4 considers the association between low dose radiation, inflammation and plaque development and progression by conducting statistical analysis utilising data on ApoE-null, ApoE-heterozygote and wild-type mice and discussing the biological pathways. Chapter 5 concludes. Certain auxiliary figures and tables (largely relating to chapters3 and 4) are presented in the appendix, while definitions for various biological and statistical terms utilized throughout are provided in the glossary at the end.

Rheumatic Heart Disease remains one of the most neglected cardiac conditions in children and young adults around the world. The pathogenesis is complex and remains elusive, and the clinical characteristics vary around the world. This thesis concentrates on different aspects of the disease in Egypt, where it is known to have a high incidence. The methodology included epidemiological studies in school children in Aswan and investigation of RHD in a population with history of RF, using newly developed echocardiographic criteria. Concomitantly, the pattern of immune response in RF and RHD was determined in serum and excised valves. In this series RF presents in children and young adults, as well as adults, (0.2-44 years, 10.69 ± 6.24) with polyarthritis being the most common clinical presentation (87.9%) and recurrences of RF being very common (98.2%). RHD affected 23 in 1000 school children in Aswan with over 90% of the cases being subclinical and developed in up to 69.2% of the individuals with history of RF, predominantly as mitral regurgitation. Risk factors for the development and severity of RHD were shown to be low disease awareness, non-compliance to penicillin prophylaxis or a regimen of longer than 15-days. Resistance to antibiotic regimens, including Penicillin and Vancomicin seems to lead to development and recurrences of RF in Egypt. This series showed the presence of immune activation and ongoing immunological reaction in an apparently quiescent phase of the disease with distortion of normal valvular architecture, histology and composition. This work has served to define the epidemiology, pattern of disease, immune reponse and predisposing factors in a population with no previous data, also contributing to the improvement of the echocardiographic diagnostic criteria. Standardization of the criteria will allow comparison of prevalence in different areas and improve case detection.

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Background: Acute myocardial infarction (AMI) is a major public health concern. There are limited recent national-level population-based epidemiological data on AMI in England. As a result, the current burden of disease is difficult to quantify. Aim: This thesis addresses gaps in knowledge on AMI in England. It aims to provide a comprehensive analysis of AMI epidemiology over the last decade. Methods: This is a population-based study using person-linked routine hospital and mortality data for England for the period from 1 April 1998 to 31 March 2008. Main outcome measures include: trends in event rate, case fatality, and mortality for AMI, as well as trends in characteristics of, and hospital care for, the AMI patient population between 1999 and 2007; rates of occurrence and case fatality for first and recurrent AMI in 2007; and five-year survival and risk of a second AMI for 2003 to 2007. Results: Total age-standardised AMI mortality rate fell by around half, while the age-standardised event rate and case fatality rate each declined by around one third between 1999 and 2007. Approximately half of the decline in AMI mortality was attributed to a decline in event rate and half to improved survival. During the 2000s, the hospitalised AMI patient population became increasingly elderly, presented with more comorbidities, underwent more revascularisation procedures, and spent less time in hospital. In 2007, approximately 90,000 AMIs occurred in England, of which around one third were fatal, one in seven were reinfarctions, and three quarters were AMIs in those aged 65 years and older. Among 30-day survivors of a first AMI, around one in three men and one in four women died within five years, and about one in eight men and one in six women experienced a second AMI in the same time period. Conclusions: There have been substantial improvements in AMI occurrence, survival, and mortality over the last decade in England. This was driven by improvements in prevention and acute medical treatment. The results in this thesis emphasise the importance of both.