Ostberg, J.E.; (2006) Characterisation of cardiovascular risk in adults with Turner Syndrome. Doctoral thesis , University of London.

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Abstract

Turner Syndrome (TS) results from the complete or partial absence of one X chromosome in females. Short stature and gonadal dysgenesis are characteristic, with increased risks of cardiovascular disease, diabetes and obesity. This thesis investigates the prevalence and pathogenesis of factors contributing to cardiovascular risk. Because women with TS differ from normals in terms of their X-chromosome defect and oestrogen deficiency, they were compared to similarly-aged normal women, and a second control group of similarly-aged women with 46,XX oestrogen deficiency was also recruited. A cross-sectional study investigated the spectrum of structural disease in the heart, aorta and conduit vessels using various imaging techniques. Intima media thickness (IMT), arterial stiffness and endothelial function were also assessed. Progression of aortic dilatation was investigated in a longitudinal echocardiography study. Metabolic abnormalities in TS were investigated by measuring anthropometric parameters and serum markers of adiposity and comparing them in all three groups. Adipose tissue distribution was further investigated in a subgroup of women with TS and normal controls. A longitudinal oestrogen dose-ranging study was performed in women with TS and 46,XX primary amenorrhoea to assess oestrogen effects on various parameters pertaining to cardiovascular risk. Women with TS had greater height-adjusted arterial diameters than controls, and greater IMT, the latter amenable to reduction by increasing doses of oestrogen. The rate of aortic dilatation was greater than in the normal population. Endothelial function did not differ significantly. Women with TS have some features of the metabolic syndrome, but fasting insulin, glucose and leptin concentrations are surprisingly low, despite increased C-reactive protein and Interleukin-6 concentrations, greater central obesity and increased visceral fat than controls. Age, bicuspid aortic valve, blood pressure and oestrogen status were the most important predictors of cardiovascular disease in TS. This knowledge should aid identification of therapeutic targets to improve care in this population.

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