Nutrition and vascular function.

Abstract

Common risk factors for CVD such as hyperlipidaemia, hypertriglyceridemia, low HDL-C, obesity, insulin resistance, impaired glucose tolerance, inflammation and hypertension may increase the risk of atherosclerosis through altering vascular function. Modification of dietary intake and weight loss can ameliorate these risk factors and may impede the development of atherosclerosis. CVD risk can be assessed by measurement of both traditional e.g. lipid levels, glucose and blood pressure and novel risk markers of CVD e.g. FMD, levels of adhesion molecules, inflammatory markers and adipokines. Changes in these measurements are used to determine effects, if any, of dietary interventions. The studies in this thesis focus on the relationship between nutrition and vascular function and the effects of modifying dietary composition either with, or without weight loss. The primary hypotheses addressed were that a high saturated fat diet would have adverse effects on markers of CVD risk., that short and long term weight loss would have beneficial effects on these markers, that a conventional low fat, high glycaemic load diet would also have adverse effects on these markers and that weight loss would attenuate the BP response to salt. Six studies were conducted to address these hypotheses. The effects of saturated fat were investigated in chapters 3 and 6. In chapter 3, a high saturated fat diet impaired FMD and increased the level of the adhesion molecule Pselectin compared with a high MUFA, a high PUFA, or a low fat, high glycaemic load diet in weight stability. The high fat, high glycaemic load caused increases of 23-39% in TG and decreases of 10-15% in HDL-C but despite these adverse effects there was no change in FMD. In chapter 6, subjects on a very low carbohydrate/high saturated fat diet lost approximately 1 kg more weight over 8 weeks than those on a conventional low fat diet. While other CVD risk factors, glucose, insulin, E and P-selectin, ICAM-1 and PAI-1 levels all improved FMD did not change in either diet. Reductions in LDL-C and CRP were greater on the conventional diet. The effects of weight loss on CVD risk factors were also investigated in the studies in chapters 4, 5, 7 & 8. In chapter 4, moderate weight loss using 2 different low fat diets resulted in improvements in PAI-1 and sICAM-1 but there was no change in FMD. Similarly in chapter 5 weight loss on a low carbohydrate/low saturated fat diet did not change FMD but there were other benefits including reductions in glucose and insulin, LDL-C, adhesion molecules, VCAM1 and ICAM1. Adiponectin did not change after short term weight loss in either of the studies in chapters 5 or 6. In chapter 7 salt loading increased ambulatory day time BP and this response was not altered by short term moderate weight loss. The long term effects of weight loss were investigated in chapters 5, 7 and 8. In chapter 5, after 52 weeks, there was sustained weight loss of 5% but no change in FMD while adiponectin levels increased and LDL-C and insulin were substantially reduced. In chapter 7 the BP response to salt loading remained unchanged despite weight loss maintenance. Finally in chapter 8 weight loss was predicted by protein intake and there were reductions in CVD risk demonstrated by decreases in insulin, TG and CRP and increases in HDL-C. The studies in this thesis demonstrate that moderate weight loss has beneficial effects on traditional and novel cardiovascular disease risk markers but does not have a beneficial effect on FMD regardless of dietary composition. A high saturated fat diet has detrimental effects on novel CVD risk markers in weight stability but weight loss attenuates this effect. A high saturated fat diet may have detrimental effects on adhesion molecules in weight stability and may attenuate the beneficial effects of weight loss on LDL-C and CRP. Moderate long term weight loss maintenance has beneficial effects on most but not all CVD risk markers.