Abstract/Summary

Replacement of saturated fat (SFA) with unsaturated fats is recognised as an effective strategy to lower cardiovascular disease (CVD) risk; however, the optimal type of fat is unclear. The majority of studies examining the effects of dietary fat composition on lipids and vascular function have been conducted in the fasting state, with very little known about the acute effects of meal fat composition on postprandial lipaemia. This is particularly important since individuals spend up to 18 h in the postprandial (fed) state, with non-fasting triacylglycerollevels now recognised as an important CVD risk factor in women. However, conclusions from my literature review revealed that little is known about the effects ofmeal fat composition on postprandial lipaemia and vascular function in postmenopausal women, an understudied subgroup ofthe population at increased CVD risk. It was hypothesised that, relative to test meals rich in SFA, those rich in monounsaturated (MUFA) or n-6 polyunsaturated fat (n-6 PUFA) would improve vascular function, postprandial lipaemia and other CVD risk markers, with differential responses dependent on the Glu298Asp polymorphism (eNOS genotype) and APOLIPOPROTEIN E (APOE) (epsilon) genotype in postmenopausal women. In a double-blind, randomised, cross-over, postprandial study, 32 postmenopausal women consumed sequential test meals (0 min, 50 g fat; 330 min, 30 g fat) rich in SFA (butter), MUFA fat (olive oil and MUFA-rich spreads) or n-6 PUFA fat (safflower oil and n-6 PUFA-rich spreads) on three separate occasions, each 4-6 weeks apart. Postprandial flow-mediated dilatation (FMD, primary outcome measure), laser Doppler imaging and digital volume pulse responses were not different after consumption ofthe test fats. For diastolic blood pressure, there was a significantly greater reduction in the incremental area under the curve (IAUC) for the postprandial response after the MUFA than SFA-rich meals (P=0.009), with a similar trend found for systolic blood pressure (P=0.012). These findings were linked with a greater reduction in the IAUC for postprandial plasma nitrite (a biomarker for nitric qxide, an important vasodilator) after the SFA than MUF A¬rich meals (P=O.O10). An effect of meal fat composition was also evident on the postprandial intracellular adhesion molecule response, with a greater reduction after the n-6 PUF A than SFA and MUFA-rich (P≤O.OO1) meals. There was little impact of the different dietary fats on postprandial lipid, glucose and insulin responses, although a significant meal fat effect was evident for postprandial IL-1ß production by ex-vivo whole blood culture lipopolysaccharide (LPS)-stimulated blood samples (a real time measure of inflammation), with higher concentrations observed after the SFA than MUFA and n-6 PUFA-rich meals (P<O.OOOl). When the data were stratified according to genotype, the eNOS Glu298Asp polymorphism was revealed to be a likely determinant of the inter-individual variability in the postprandial % FMD (P=O.019) and insulin responses to acute dietary fat intake. As expected APOE genotype was associated with baseline fasting plasma lipids and inflammatory markers (C-reactive protein) but our study also revealed a novel impact on arterial stiffness. However, there was limited impact of APOE genotype on cardio-metabolic risk markers in response to acute and chronic fat manipulation. In conchision, this PhD has shown for the first time that meal fat composition has a significant impact on blood pressure, plasma nitrite, markers of endothelial activation, and ex-vivo IL-1ß cytokine production, but no effect on postprandial lipaemia in postmenopausal women. The eNOS Glu298Asp polymorphism and APOE genotype may also be important in relation to vascular function in this population group, and warrant further investigation. Overall, these findings will contribute to the evidence base for dietary fat recommendation and may be important in identifying population subgroups with greater responsiveness to the beneficial effects of targeted dietary fatty acid manipulation through personalised nutrition.