Abstract
In recent years the prevalence of obesity, physical inactivity, sedentary behaviour and low cardiorespiratory fitness in Western countries has increased rapidly. These variables are independently associated with cardiovascular disease risk and/or mortality. Atherosclerosis begins in childhood and endothelial dysfunction is its earliest detectable manifestation. Endothelial dys/function can be quantified using flow mediated dilation (FMD). The primary aim of this thesis was to investigate childhood associations between endothelial function and a range of modifiable and non-modifiable CV risk factors. We sought to provide novel information regarding relationships between physical activity, sedentary behaviour, body composition, cardiorespiratory fitness and the heritability of endothelial function. In addition, we sought to explore the issue of the scaling of vascular outcomes for body size and composition. Study one (Chapter 4) addressed the question of scaling, by evaluating the efficacy of scaling vascular dimensions and FMD for different body composition variables using allometric and ratio procedures, with the aim of producing size independent vascular indices. Our data indicate that, if between-group comparisons of baseline brachial artery diameter are to be undertaken, appropriate, allometric scaling for measures of lean or total mass may need to be adopted. The application of such scaling to FMD data is debatable as the associations between FMD and body composition variables were very weak. We therefore concluded that the adoption of scaling FMD for body composition variables cannot be advocated until further research has been undertaken. Studies 2 and 4 (Chapters 5 and 7) assessed cross-sectional relationships between FMD and modifiable CV risk factors in young people. We examined associations between FMD and objective measurements of body composition, cardiorespiratory fitness, physical activity levels and sedentary behaviour. We observed a weak association between percentage body fat and FMD and no further relationships across cohort. However, depressed endothelial function was significantly related to, and predicted by high intensity physical activity. The relationship between FMD and high intensity PA was further reinforced by the findings from studies 3 and 4 (Chapters 6 and 7), which aimed to address the issue of seasonal variation in FMD and determine its predictors. The studies demonstrated that seasonal decline in vascular function was associated with, and predicted by, a change in high intensity PA but no other variables. These findings demonstrate, for the first time, that high-intensity PA may be an important determinant of vascular dys/function in children. The ramifications of these findings are that interventions aimed at improving vascular health in children may need to be refocused to bring about a progressive increase in physical activity, specifically high intensity physical activity, rather than reducing obesity or sedentary time per se. Finally, studies 5 and 6 (Chapters 8 and 9) utilised a classic twin study design to explore the role of genetics in the modulation of FMD. Through the comparison of intra-twin pair differences in mono- and di-zygotic twins, we were able to provide information relating to the genetic influence on FMD and calculate a heritability estimate. We concluded that, although a one-off measurement of endothelial function is under some level of genetic control, environmental factors may have a larger influence in the determination of FMD in young people (study 5).In study 6, twins undertook 8 weeks of aerobic exercise training. In this study, intra-twin differences in the adaptation of FMD were compared to changes in other variables. The results highlighted a greater similarity between MZ twins than DZ twins in the change in FMD, suggesting that exercise-induced improvements in FMD may be highly genetically determined. Taken together, the findings of this thesis infer that, whilst a genetic predisposition to endothelial dysfunction may exist, interventions that aim to increase high intensity physical activity have the potential to enhance vascular health in young people at risk of endothelial impairment and future development of atherosclerotic diseases
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