Background Diets high in saturated fatty acids (SFAs) and greater abdominal obesity are both associated with raised low-density lipoprotein cholesterol (LDL-C) concentrations, an independent cardiovascular disease (CVD) risk marker. Although reducing SFA intake is a public health strategy for CVD prevention, the role of body fat distribution on the relationship between SFA and LDL-C is unclear. Therefore, our objective was to investigate whether the association between dietary SFAs and LDL-C concentrations is related to body composition. Methods In the BODYCON (impact of physiological and lifestyle factors on body composition) study, 409 adults [mean age 42 ± 16 years and median BMI of 23.5 (21.5–25.9) kg/m2] underwent a measure of body composition by dual energy x-ray absorptiometry, assessment of habitual dietary intake using a 4-day weighed food diary and physical activity level using a tri-axial accelerometer. Blood pressure was measured, and a fasting blood sample was collected to determine cardiometabolic disease risk markers. Correlations between body composition, circulating risk markers and dietary macronutrients were assessed prior to multivariate regression analysis. The effect of increasing intakes of dietary SFA on outcome measures was assessed using ANCOVA after adjusting for covariates. Results Abdominal visceral adipose tissue (VAT) mass was moderately positively correlated with total cholesterol (TC), LDL-C, systolic blood pressure (SBP), diastolic blood pressure and HOMA-IR (rs = 0.25–0.44, p < 0.01). In multiple regression analysis, 18.3% of the variability in LDL-C was explained by SFA intake [% total energy (TE)], abdominal VAT mass, carbohydrate%TE and fat%TE intakes. When data were stratified according to increasing SFA%TE intakes, fasting TC, LDL-C and non-high-density lipoprotein-cholesterol were higher in Q4 compared with Q2 (p ≤ 0.03). SBP was higher in Q4 versus Q3 (p = 0.01). Android lean mass was also higher in Q3 versus Q1 (p = 0.02). Other anthropometric and CVD risk markers were not different across quartile groups. Conclusions Although dietary SFA was found to explain 9% of the variability in LDL-C, stratification of data according to quartiles of SFA intake did not reveal a dose-dependent relationship with LDL-C concentration. Furthermore, this association appeared to be independent of abdominal obesity in this cohort. Clinical Trail registration: Trial registration: clinicaltrials.gov as NCT02658539. Registered 20 January 2016, https://clinicaltrials.gov/ct2/show/NCT02658539.

Body mass index (BMI) has been suggested to play an important role in the relationship between the APOLIPOPROTEIN (APO)E genotype and cardiovascular disease (CVD) risk. Using data from the BODYCON cross-sectional study (n = 360 adults) we assessed the association between body composition and CVD risk markers according to APOE genotype, with examination of the role of BMI. In this study cohort, the APOE2/E3 group had lower fasting blood lipids than APOE4 carriers and APOE3/E3 group (p ≤ 0.01). After stratifying the group according to BMI, APOE4 carriers in the normal BMI subgroup had a higher lean mass compared with the APOE3/E3 group (p = 0.02) whereas in the overweight/obese subgroup, the android to gynoid percentage fat ratio was lower in APOE4 carriers than APOE3/E3 group (p = 0.04). Fasting lipid concentrations were only different between the APOE2/E3 and other genotype groups within the normal weight BMI subgroup (p ≤ 0.04). This finding was associated with a lower dietary fibre and a higher trans-fat intake compared with APOE4 carriers, and a lower carbohydrate intake relative to the APOE3/E3 group. Our results confirm previous reports that BMI modulates the effect of APOE on CVD risk markers and suggest novel interactions on body composition, with diet a potential modulator of this relationship.

Endothelial dysfunction, combined with inflammation, plays a significant role in the development of atherosclerosis and risk of cardiovascular disease (CVD) (1) . Reduction in dietary saturated fatty acid (SFA) intake is a key dietary recommendation for CVD risk reduction (2) . However, it remains unclear whether monounsaturated fatty acids (MUFA) or n-6 polyunsaturated fatty acids (n-6 PUFA) are the optimal fatty acids to replace dietary SFA. The aim of this study was to determine the effects of substitution of SFA with either MUFA or n-6 PUFA on circulating markers of endothelial function and inflammation in men and women at increased risk of developing CVD.A total of 195 men and women at increased CVD risk (mean age 44 (sd 10) years and BMI 26.9 (SD 4.0) kg/m 2 ) participated in a 16-week, parallel, randomised, controlled, single-blinded intervention study (DIVAS -(Dietary Intervention and VAscular function Study; ClinicalTrials.gov NCT01478958). Participants were randomly assigned (minimised for gender, age, BMI and CVD risk score) to one of the following isoenergetic diets: SFA-rich (target composition: 36 % of total energy (%E) as total fat, 17 %E SFA, 11 %E MUFA, 4%E n-6 PUFA), MUFA-rich (36% E total fat, 9 %E SFA, 19 %E MUFA, 4 %E n-6 PUFA), or n-6 PUFA-rich (36% E total fat, 9%E SFA, 13 %E MUFA, 10 %E n-6 PUFA). A flexible dietary model was developed to deliver the dietary interventions in which exchangeable fats in the habitual diet were replaced by study foods (spreads, oils, snacks) with a specific fatty acid composition. Vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a), E-Selectin, P-Selectin, von Willebrand factor (vWf) and C-Reactive protein (CRP) were determined by immunoassays in the fasting blood samples collected at baseline and following 16 weeks of intervention.Blood E-Selectin levels (P = 0.025) were significantly influenced by dietary fat composition. It was observed that there was a differential response after the MUFA-rich compared with the SFA-rich diet in which E-Selectin levels decreased after MUFA (Week16-Week0: -2.33 (SEM 0.91) ng/ml) compared to the increase following the SFA-rich diet (Week16-Week0: 1.27 (SEM 1.01) ng/ml), (P = 0.008). There were no significant effects of treatment on blood VCAM-1, ICAM-1, IL-6, TNF-a, P-Selectin, vWf and CRP.In conclusion, this study suggests that replacement of dietary SFA with MUFA may have beneficial effects on circulating levels of E-Selectin.

Endothelial dysfunction has been recognised as an early modifiable marker in the development of atherosclerosis and risk of cardiovascular disease (CVD) (1) . A central public health strategy for the reduction of CVD includes the reduction in dietary saturated fatty acid (SFA) intake (2) . However, it remains unclear whether monounsaturated fatty acids (MUFA) or n-6 polyunsaturated fatty acids (n-6 PUFA) are the optimal fatty acids to replace dietary SFA. The aim of this study was to determine the effects of substitution of SFA with either MUFA or n-6 PUFA on measures of endothelial function, arterial stiffness and blood pressure in men and women at increased risk of developing CVD.A total of 195 men and women at increased CVD risk (mean age 44 (SD 10) years and BMI 26.9 (SD 4.0) kg/m 2 ) participated in a 16-week, parallel, randomised, controlled, single-blinded intervention study (DIVAS -(Dietary Intervention and VAscular function Study; ClinicalTrials.gov NCT01478958). Participants were randomly assigned (minimised for gender, age, BMI and CVD risk score) to one of the following isoenergetic diets: SFA-rich (target composition: 36% of total energy (%E) as total fat, 17%E SFA, 11%E MUFA, 4%E n-6 PUFA), MUFA-rich (36%E total fat, 9%E SFA, 19%E MUFA, 4%E n-6 PUFA), or n-6 PUFA-rich (36%E total fat, 9%E SFA, 13%E MUFA, 10%E n-6 PUFA). A flexible dietary model was developed to deliver the dietary interventions in which exchangeable fats in the habitual diet were replaced by study foods (spreads, oils, snacks) with a specific fatty acid composition. Flow-Mediated Dilatation (FMD) and Laser Doppler imaging (LDI) with iontophoresis were measured for assessing the endothelial function of the macro-and microcirculation, respectively. Pulse Wave Velocity/Analysis (PWV/PWA), Digital Volume Pulse (DVP) (measures of arterial stiffness) and 24-h Ambulatory Blood Pressure (24-h ABP) were also measured at baseline and following 16 weeks of intervention.A significant deterioration in the FMD response, endothelium-dependent vasodilation of the microvascular circulation (LDI) and mean night SBP and DBP was observed following the SFA-rich diet relative to baseline (P < 0.05), but not following either n-6 PUFA or MUFA-rich diet. A significant diet interaction was observed for mean night SBP where replacement of SFA with MUFA attenuated the increase observed with SFA (P < 0.05).In conclusion, this study showed that dietary SFA had a detrimental effect on vascular reactivity and blood pressure in a group at risk from CVD, which was not observed following the diets rich in unsaturated fatty acids. These data support current public health recommendations to reduce dietary SFA intake as a strategy for CVD risk reduction.