Are definitions of adiposity appropriate for identification of cardiovascular disease risk in South Asian populations?

South Asian populations living in the UK have a high prevalence of the metabolic syndrome, cardiovascular disease (CVD) and type 2 diabetes which impacts greatly on the morbidity and mortality of this ethnic group. The identification of ‘at risk’ individuals is essential to initiate reventative treatment. However, this is considerably hindered by the lack of appropriate cut-off values for anthropometric measures. CVD risk is significantly higher at a lower body mass index (BMI) in many Asian groups compared with Caucasians and adiposity (particularly central deposition) is higher at similar BMI levels. The definition of adiposity in Asians needs to be firmly established and appropriate lower BMI and waist circumference cut-offs implemented in ethnic subpopulations to facilitate appropriate treatment strategies.

Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production

Background: Dietary isoflavones are thought to be cardioprotective because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease. Objective: Our aim was to investigate the effects of isolated soy isoflavones on inflammatory biomarkers [von Willebrand factor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin, monocyte chemoattractant protein 1, C-reactive protein (CRP), and endothelin 1 concentrations]. Differences with respect to single-nucleotide polymorphisms in selected genes [estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta [ER beta (AluI) and ER beta[cx] (Tsp5091), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), and cholesteryl ester transfer protein (TaqIB)] and equol production were investigated. Design: One hundred seventeen healthy European postmenopausal women participated in this randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1;50 mg/d) or placebo cereal bars were consumed for 8 wk, with a washout period of 8 wk between the crossover. Plasma inflammatory factors were measured at 0 and 8 wk of each study arm. Results: Isoflavones improved CRP concentrations [odds ratio (95% Cl) for CRP values >1 mg/L for isoflavone compared with placebo: 0.43 (0.27, 0.69)]; no significant effects of isoflavone treatment on other plasma inflammatory markers were observed. No significant differences in the response to isoflavones were observed according to subgroups of equol production. Differences in the VCAM-1 response to isoflavones and to placebo were found with ER beta AluI genotypes. Conclusion: Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ER beta gene polymorphic subgroup.

Effects of chronic and acute fruit and vegetable juice consumption on cardiovascular disease risk factors

Diets low in fruit and vegetables are reportedly responsible for 2.7 million deaths annually from cardiovascular diseases (CVD) and certain cancers. A daily fruit and vegetable intake of five 80 g portions is recommended for chronic disease prevention. However, in the UK, average adult consumption is less than three portions. It is suggested that fruit juice should only count as one portion. However, fruit juices are a beneficial source of phytochemicals. The preliminary results of two randomized, controlled, crossover, dietary intervention studies investigating the effects of chronic and acute consumption of fruit and vegetable puree and juice based drinks (FVPJ) on bioavailability, antioxidant status, vascular reactivity, and risk factors for CVD are reported. In the first study, 39 volunteers consumed 200 ml FVPJ, or fruit-flavoured control, daily for six weeks. In the second study, 24 volunteers consumed 400 mL FVPJ, or sugar-matched control, on the morning of the study day. Blood and urine samples were collected throughout both studies and real-time measurements of vascular tone were performed using laser Doppler imaging with iontophoresis. Overall, the studies showed that the fruit and vegetable puree and juice based drink increased dietary phytochemicals. There was a trend towards increased vasodilation following both acute and chronic fruit juice consumption. Measurements of antioxidant status, oxidative stress and other cardiovascular disease risk factors are currently being determined.

Daily consumption of an aqueous green tea extract supplement does not impair liver function or alter cardiovascular disease risk biomarkers in healthy men

Regular consumption of green tea polyphenols (GTP) is thought to reduce the risk of cardiovascular disease (CVD) but has also been associated with liver toxicity. The present trial aimed to assess the safety and potential CVD health beneficial effects of daily GTP consumption. We conducted a placebo-controlled parallel study to evaluate the chronic effects of GTP on liver function and CVD risk biomarkers in healthy men. Volunteers (treatment: n = 17, BMI 26.7 +/- 3.3 kg/m(2), age 41 +/- 9 y; placebo, n = 16, BMI 25.4 +/- 3.3 kg/m(2), age 40 +/- 10 y) consumed for 3 wk 6 capsules per day (2 before each principal meal) containing green tea extracts (equivalent to 714 mg/d GTP) or placebo. At the beginning and end of the intervention period, we collected blood samples from fasting subjects and measured vascular tone using Laser Doppler lontophoresis. Biomarkers of liver function and CVD risk (including blood pressure, plasma lipids, and asymmetric dimethylarginine) were unaffected by GTP consumption. After treatment, the ratio of total:HDL cholesterol was significantly reduced in participants taking GTP capsules compared with baseline. Endothelial-dependent and -independent vascular reactivity did not significantly differ between treatments. In conclusion, the present data suggests that the daily consumption of high doses of GTP by healthy men for 3 wk is safe but without effects on CVD risk biomarkers other than the total:HDL cholesterol ratio. J. Nutr. 139: 58-62, 2009.

Postprandial lipemia and cardiovascular disease risk: interrelationships between dietary, physiological and genetic determinants

Although the independence of the association and causality has not been fully established, non-fasting (postprandial) triglyceride (TG) concentrations have emerged as a clinically significant cardiovascular disease (CVD) risk factor. In the current review, findings from three insightful prospective studies in the area, namely the Women's Health Study, the Copenhagen City Heart Study and the Norwegian Counties Study, are discussed. An overview is provided as to the likely etiological basis for the association between postprandial TG and CVD, with a focus on both lipid and non-lipid (inflammation, hemostasis and vascular function) risk factors. The impact of various lifestyle and physiological determinants are considered, in particular genetic variation and meal fat composition. Furthermore, although data is limited some information is provided as to the relative and interactive impact of a number of modulators of lipemia. It is evident that relative to age, gender and body mass index (known modulators of postprandial lipemia), the contribution of identified gene variants to the heterogeneity observed in the postprandial response is likely to be relatively small. Finally, we highlight the need for the development of a standardised ‘fat tolerance test’ for use in clinical trials, to allow the integration and comparison of data from individual studies

NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids

Objective Omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against the development of cardiovascular disease (CVD). Genotype at key genes such as nitric oxide synthase (NOS3) may determine responsiveness to fatty acids. Gene–nutrient interactions may be important in modulating the development of CVD, particularly in high-risk individuals with the metabolic syndrome (MetS). Methods Biomarkers of CVD risk, plasma fatty acid composition, and NOS3 single nucleotide polymorphism (SNP) genotype (rs11771443, rs1800783, rs1800779, rs1799983, rs3918227, and rs743507) were determined in 450 individuals with the MetS from the LIPGENE dietary intervention cohort. The effect of dietary fat modification for 12 weeks on metabolic indices of the MetS was determined to understand potential NOS3 gene–nutrient interactions. Results Several markers of inflammation and dyslipidaemia were significantly different between the genotype groups. A significant gene–nutrient interaction was observed between the NOS3 rs1799983 SNP and plasma n-3 PUFA status on plasma triacylglycerol (TAG) concentrations. Minor allele carriers (AC + AA) showed an inverse association with significantly higher plasma TAG concentrations in those with low plasma n-3 PUFA status and vice versa but the major allele homozygotes (CC) did not. Following n-3 PUFA supplementation, plasma TAG concentrations of minor allele carriers of rs1799983 were considerably more responsive to changes in plasma n-3 PUFA, than major allele homozygotes. Conclusions Carriers of the minor allele at rs1799983 in NOS3 have plasma TAG concentrations which are more responsive to n-3 PUFA. This suggests that these individuals might show greater beneficial effects of n-3 PUFA consumption to reduce plasma TAG concentrations.

Impact of the quantity and flavonoid content of fruits and vegetables on markers of intake in adults with an increased risk of cardiovascular disease: the FLAVURS Trial

Purpose Limited robust randomised controlled trials investigating fruit and vegetable (F&V) intake in people at risk of cardiovascular disease (CVD) exist. We aimed to design and validate a dietary strategy of increasing flavonoid-rich versus flavonoid-poor F&V consumption on nutrient biomarker profile. Methods A parallel, randomised, controlled, dose–response dietary intervention study. Participants with a CVD relative risk of 1.5 assessed by risk scores were randomly assigned to one of the 3 groups: habitual (control, CT), high-flavonoid (HF) or low-flavonoid (LF) diets. While the CT group (n = 57) consumed their habitual diet throughout, the HF (n = 58) and LF (n = 59) groups sequentially increased their daily F&V intake by an additional 2, 4 and 6 portions for 6-week periods during the 18-week study. Results Compliance to target numbers and types of F&V was broadly met and verified by dietary records, and plasma and urinary biomarkers. Mean (±SEM) number of F&V portions/day consumed by the HF and LF groups at baseline (3.8 ± 0.3 and 3.4 ± 0.3), 6 weeks (6.3 ± 0.4 and 5.8 ± 0.3), 12 weeks (7.0 ± 0.3 and 6.8 ± 0.3) and 18 weeks (7.6 ± 0.4 and 8.1 ± 0.4), respectively, was similar at baseline yet higher than the CT group (3.9 ± 0.3, 4.3 ± 0.3, 4.6 ± 0.4, 4.5 ± 0.3) (P = 0.015). There was a dose-dependent increase in dietary and urinary flavonoids in the HF group, with no change in other groups (P = 0.0001). Significantly higher dietary intakes of folate (P = 0.035), non-starch polysaccharides (P = 0.001), vitamin C (P = 0.0001) and carotenoids (P = 0.0001) were observed in both intervention groups compared with CT, which were broadly supported by nutrient biomarker analysis. Conclusions The success of improving nutrient profile by active encouragement of F&V intake in an intervention study implies the need for a more hands-on public health approach.

Flavonoid-rich fruits and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease – FLAVURS: a randomized controlled trial

BACKGROUND: Observed associations between increased fruit and vegetable (F&V) consumption, particularly those F&Vs that are rich in flavonoids, and vascular health improvements require confirmation in adequately powered randomized controlled trials. OBJECTIVE: This study was designed to measure the dose-response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual F&V intakes and vascular function and other cardiovascular disease (CVD) risk indicators. DESIGN: A single-blind, dose-dependent, parallel randomized controlled dietary intervention study was conducted. Male and female low-F&V consumers who had a ≥1.5-fold increased risk of CVD (n = 174) were randomly assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every 6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO), vascular function, and inflammation were determined at baseline and at 6, 12, and 18 wk. RESULTS: In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with +2 portions/d (at 6 wk) and reduced C-reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion molecule (P = 0.0468) with +4 portions/d (at 12 wk). HF F&Vs increased plasma NO (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO (P = 0.0299) in the control group. CONCLUSION: These data support recommendations to increase F&V intake to ≥6 portions daily, with additional benefit from F&Vs that are rich in flavonoids, particularly in men with an increased risk of CVD. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

Orange juice–derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease

Background: Epidemiological data suggest inverse associations between citrus flavanone intake and cardiovascular disease (CVD) risk. However, insufficient randomized controlled trial (RCT) data limit our understanding of mechanisms by which flavanones and their metabolites potentially reduce cardiovascular (CV) risk factors. Objective: We examined the effects of orange juice or a dose-matched hesperidin supplement on plasma concentrations of established and novel flavanone metabolites and their effects on CV risk biomarkers in men at moderate CVD risk. Methods: In an acute, randomized, placebo-controlled crossover trial, 16 fasted participants (aged 51-69 y) received orange juice or a hesperidin supplement (both providing 320 mg hesperidin) or control (all matched for sugar and vitamin C content). At baseline and 5 h post-intake, endothelial function (primary outcome), further CV risk biomarkers (i.e. blood pressure, arterial stiffness, cardiac autonomic function, platelet activation and NADPH oxidase gene expression) and plasma flavanone metabolites were assessed. Prior to each intervention, a diet low in flavonoids, nitrate/nitrite, alcohol and caffeine was followed and a standardized low-flavonoid evening meal was consumed. Results: Orange juice intake significantly elevated mean (± SEM) plasma concentrations of 8 flavanone (1.75 ± 0.35 µmol/L, P < 0.0001) and 15 phenolic metabolites (13.27 ± 2.22 µmol/L, P < 0.0001) compared with control at 5 h post-consumption. Despite increased plasma flavanone and phenolic metabolite concentrations, CV risk biomarkers were unaltered. Following hesperidin supplement intake, flavanone metabolites were not different to control, suggesting altered absorption/metabolism compared with the orange juice matrix. Conclusions: Following single-dose flavanone intake within orange juice, we detected circulating flavanone and phenolic metabolites collectively reaching a concentration of 15.20 ± 2.15 µmol/L but observed no effect on CV risk biomarkers. Longer-duration RCTs are required to further examine the previous associations between higher flavanone intakes and improved cardiovascular health and to ascertain the relative importance of food matrix and flavanone-derived phenolic metabolites.

Omega-3 fatty acids, cardiovascular disease and stability of atherosclerotic plaques

Long-chain n-3 polyunsaturated fatty acids are found in oily fish and in fish oils and similar preparations. Substantial evidence from epidemiological and case-control studies indicates that consumption of fish, oily fish and long-chain n-3 fatty acids reduces risk of cardiovascular mortality. Secondary prevention studies using long-chain n-3 fatty acids in patients post-myocardial infarction have shown a reduction in total and cardiovascular mortality with an especially potent effect on sudden death. Long-chain n-3 fatty acids have been shown to beneficially modify a range of cardiovascular risk factors, which may result in primary cardiovascular prevention. However, reduced non-fatal and fatal events and a reduction in sudden death probably involve other mechanisms. Reduced thrombosis following long-chain n-3 fatty acids may play a role. A decrease in arrhythmias is a favoured mechanism of action of long-chain n-3 fatty acids and is supported by cell culture and animal studies. However human trials using implantable cardiac defibrillators have produced inconsistent findings and a recent meta-analysis does not support this mechanism of action. An alternative mechanism of action may be stabilisation of atherosclerotic plaques by long-chain n-3 fatty acids. This is suggested by one published human study which showed that incorporation of long-chain n-3 fatty acids into plaques collected at carotid endarterectomy resulted in fewer macrophages in the plaque and a morphology indicative of increased stability. These findings are supported from observations in an animal model and suggest that the primary effect of long-chain n-3 fatty acids might be on macrophages within the plaque.

Supplementation with fruit and vegetable soups and beverages increases plasma carotenoid concentrations but does not alter markers of oxidative stress or cardiovascular risk factors

This study was aimed at determining whether an increase of 5 portions of fruits and vegetables in the form of soups and beverages has a beneficial effect on markers of oxidative stress and cardiovascular disease risk factors. The study was a single blind, randomized, controlled, crossover dietary intervention study. After a 2-wk run-in period with fish oil supplementation, which continued throughout the dietary intervention to increase oxidative stress, the volunteers consumed carotenoid-rich or control vegetable soups and beverages for 4 wk. After a 10-wk wash-out period, the volunteers repeated the above protocol, consuming the other intervention foods. Both test and control interventions significantly increased the % energy from carbohydrates and decreased dietary protein and vitamin B-12 intakes. Compared with the control treatment, consumption of the carotenoid-rich soups and beverages increased dietary carotenoids, vitamin C, alpha-tocopherol, potassium, and folate, and the plasma concentrations of alpha-carotene (362%), beta-carotene (250%) and lycopene (31%) (P < 0.01) and decreased the plasma homocysteine concentration by 8.8% (P < 0.01). The reduction in plasma homocysteine correlated weakly with the increase in dietary folate during the test intervention (r = -0.35, P = 0.04). The plasma antioxidant status and markers of oxidative stress were not affected by treatment. Consumption of fruit and vegetable soups and beverages makes a useful contribution to meeting dietary recommendations for fruit and vegetable consumption.

Dietary fat composition and cardiovascular disease

Cardiovascular disease (CVD), which includes coronary heart disease and stroke, remains the major killer in the EU, being responsible for 42% of total mortality. The amount and composition of dietary fat is arguably the most important dietary factor contributing to disease risk. A significant body of consistent evidence indicates that a decrease in dietary saturated fat:unsaturated (polyunsaturated + monounsaturated) ratio and an increased intake of long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) found in fish, is cardioprotective. Furthermore, although the evidence is currently less convincing, such a strategy is also likely to improve insulin sensitivity, the central metabolic defect in diabetes. Currently in the UK only 12% of men, 17% of women and 8% of children have an SFA intakes <10% of energy. The average intake of LC n-3 PUFA is <0.2 g/day, which is less than half the current conservative recommendation of a minimum of 0.45 g/day. Public health strategies to reverse these dietary fatty acid imbalances, aimed at educating and motivating the consumer and making affordable and acceptable food products with an ‘enhanced’ fatty acid profile more widely available, must remain a public health priority in the ‘fight’ against CVD.

Functional food, blood lipids and cardiovascular disease. Part 1: probiotics

For the past 20 years, the focuses of public health strategies for reducing the risk of cardiovascular disease (CVD) have been aimed at lowering cholesterol levels. However recent findings have highlighted not only cholesterol but also triacylglycerol as a lipid risk factor for CVD. Dietary strategies which are able to reduce these circulating lipid levels, but which are able to offer long-term efficacy comparable with effective drug treatments, are currently being sought. One dietary strategy that has been proposed to benefit the lipid profile involves the supplementation of the diet with probiotics (Part 1), prebiotics and synbiotics (Part 2), which are mechanisms to improve the health of the host by supplementation and/or fortification of certain health promoting gut bacteria. Probiotics in the form of fermented milk products have been shown to have cholesterol-lowering properties, whereas non-digestible fermentable prebiotics have been shown to reduce triacylglycerol levels in animal studies. However in humans studies, there have been inconsistent findings with respect to changes in lipid levels with both prebiotics and probiotics although on the whole there have been favourable outcomes.

Personalized nutrition for the prevention of cardiovascular disease: a future perspective

Cardiovascular disease (CVD) is responsible for significant morbidity and mortality in the Western and developing world. This multifactorial disease is influenced by many environmental and genetic factors. At present, public health advice involves prescribed population-based recommendations, which have been largely unsuccessful in reducing CVD risk. This is, in part, due to individual variability in response to dietary manipulations, that arises from nutrient-gene interactions (defined by the term 'nutrigenetics'). The shift towards personalized nutritional advice is a very attractive proposition, where, in principle, an individual can be given dietary advice specifically tailored to their genotype. However, the evidence-base for the impact of interactions between nutrients and fixed genetic variants on biomarkers of CVD risk is still very limited. This paper reviews the evidence for interactions between dietary fat and two common polymorphisms in the apolipoprotein E and peroxisome proliferator-activated receptor-gamma genes. Although an increased understanding of how these and other genes influence response to nutrients should facilitate the progression of personalized nutrition, the ethical issues surrounding its routine use need careful consideration.