Non-invasive studies of arterial physiology in children and adults at risk of atherosclerosis

Atherosclerosis is the leading cause of death in the Western World. In clinical practice, treatment and risk factor modification usually begin only after complications of advanced disease have occurred. Pathology studies, however, have shown that atherogenesis begins much earlier and may be evident in the first decade of life. This thesis describes the development of a non-invasive method to study arterial physiology in children and adults, in order to detect early signs of vascular disease in-vivo, in presymptomatic subjects. Endothelial dysfunction is a key early event in the initiation and progression of atherosclerosis in experimental studies, preceding formation of plaques. We have used high resolution ultrasound to study endothelial and smooth muscle function in systemic arteries in man. Arterial diameter responses to reactive hyperaemia (with increased flow causing endothelium-dependent dilatation) were compared to the responses to sublingual nitroglycerine (which acts independently of endothelial function). Phantom studies have confirmed the precision of diameter measurements (accurate to 0.1-0.2mm), and serial studies have shown reproducible results within patients between visits (coefficient of variation ≅2.0%). Studies on over 200 control subjects without vascular risk factors showed that flow- mediated dilatation (FMD) occurs, and is inversely related to vessel size (r=-0.80,