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Title: Interventions in patients at high cardiovascular risk
Author: González Seña, Susana
ISNI:       0000 0004 2740 7943
Awarding Body: University of Hull
Current Institution: University of Hull
Date of Award: 2011
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Cardiovascular disease is a major cause of premature death in UK and an important contributor to escalating health costs. The risk of suffering a cardiovascular event is associated with multiple risk factors that can cluster in different pathological conditions such as type 2 diabetes, polycystic ovarian syndrome (PCOS) and hypopituitarism. Therefore, interventions in these patients at high risk of cardiovascular disease can be potentially beneficial to improve cardiovascular health and this is explored in the different chapters of this thesis. Current knowledge of what constitutes cardiovascular risk is reviewed in chapter one and the methods used to conduct the studies presented in this thesis are described in chapter two. Chapter three evaluates the effects of social deprivation in lipid management in a community setting. This study analysed lipid measurements and lipid lowering agents prescriptions across 34 electoral wards in Kingston Upon Hull and East Riding of Yorkshire with different deprivation scores. A ward is a primary territorial unit which represent a part of an electoral district. It showed that both lipid measurements and prescriptions were similar in deprived and wealthier wards (correlation values: r=0.18 and r=0.50 respectively) and this might represent service under provision in poorer areas. The effect of isoflavones on insulin resistance and cardiovascular risk factors in postmenopausal women with diet controlled type 2 diabetes is studied in chapter four. Oral supplementation with 132 mg/day for a three months period has no significant effects modulating glycaemic control (glucose, p=0.59; HbA1c, p=0.58), insulin 12 resistance (HOMA-IR method, p=0.24) or cardiovascular risk factors (total cholesterol, p=0.96; HDL cholesterol, p=0.93; LDL cholesterol, p=0.97; triglycerides, p=0.74; body mass index, p=0.97; systolic blood pressure, p=0.35 and diastolic blood pressure, p=0.38). This implies that either a combination of soy protein and isoflavones or soy protein on their own are needed to induce the beneficial effect reported in the literature. Chapter five evaluates the combined effect of a hypocaloric diet (1500 kcal/day) and metformin (500mg three times a day) on cardiovascular risk factors and on the biological variation of lipids in obese patients with PCOS. This intervention improved central obesity (waist/hip ratio, p=0.02; body mass index, p=0.008), blood pressure (systolic blood pressure=0.02; diastolic blood pressure, p=0.009) and LDL levels (p=0.03). However, the biological variation of lipids is similar to that in health and remained unchanged with this intervention. Therefore, reference value changes obtained from healthy individuals could be used to monitor serial lipids levels i.e. in response to a therapeutic intervention. The effects of subcutaneous recombinant growth hormone (rGH) in patients with adult onset growth hormone deficiency on exercise capacity, quality of life and general cardiovascular risk factors is explored in chapter six. Three months treatment with a fixed, low dose of rGH (dose=0.4 mg/day) improved total body fat (p=0.05) and normalised plasma IGF1 (p=0.0001) without a significant effect on cardiovascular risk factors, exercise capacity or quality of life. Mitochondrial succinate dehydrogenase (SDH) increased by a 2.7 fold in both the active and placebo phases when compared with baseline, possibly related to an increase in patient’s daily activities. Finally, chapter seven analyses the biological variation of N terminal probrain natriuretic peptide (NT-proBNP) in postmenopausal women with and without type 2 diabetes. Type 2 diabetes appears to have little influence in the biological variation of this natriuretic peptide. This implies that current guidelines on the use of NT-proBNP for the screening, diagnosis and evaluation of serial results in hearth failure would be applicable in type 2 diabetes. The reference change values obtained in this study could be used to determine if two NT-proBNP levels are different due to the effect of treatment rather than their biological variation.
Supervisor: Atkin, Stephen Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine