How expensive is a cardioprotective diet? Analysis from the CRESSIDA study

AbstractObjectiveTo determine whether a cardioprotective dietary intervention based on UK dietary guidelines was more expensive than a conventional UK diet.DesignCost analysis of food records collected at baseline and after a 12-week dietary intervention of a cardioprotective diet v. conventional UK diet.SettingA randomized controlled dietary intervention study (CRESSIDA; ISRCTN 92382106) investigating the impact of following a diet consistent with UK dietary guidelines on CVD risk.SubjectsParticipants were healthy UK residents aged 40–70 years. A sub-sample of participants was randomly selected from those who completed the cardioprotective dietary intervention (n 20) or the conventional UK dietary intervention (n 20).ResultsBaseline diet costs did not differ between groups; mean daily food cost for all participants was £6·12 (sd £1·83). The intervention diets were not more expensive: at end point the mean daily cost of the cardioprotective diet was £6·43 (sd £2·05) v. the control diet which was £6·53 (sd £1·53; P=0·86).ConclusionsThere was no evidence that consumption of a cardioprotective diet was more expensive than a conventional dietary pattern. Despite the perception that healthier foods are less affordable, these results suggest that cost may not be a barrier when modifying habitual intake and under tightly controlled trial conditions. The identification of specific food groups that may be a cost concern for individuals may be useful for tailoring interventions for CVD prevention for individuals and populations.</jats:sec

Lessons from the COVID-19 pandemic to improve the health and social care and wellbeing of minoritised ethnic groups with chronic conditions or impairments: protocol for the mixed methods intersectional asset-based study CICADA

BACKGROUND: The pandemic has inequitably impacted the experiences of people living with ill health/impairments or from minoritised ethnic groups across all areas of life. Given possible parallels in inequities for disabled people and people from minoritised ethnic backgrounds, their existence before the pandemic and increase since, and the discriminations that each group faces, our interest is in understanding the interplay between being disabled AND being from a minoritised ethnic group. OBJECTIVE: The overarching aim of the CICADA project, building on this understanding, is to improve pandemic and longer-term support networks and access to and experiences of care, services and resources for these under-served groups, both during the pandemic and longer term, reducing inequities and enhancing social, health and wellbeing outcomes. METHODS: This mixed methods study involves three 'sweeps' of a new UK survey, secondary analyses of existing cohort and panel surveys, a rapid scoping review, a more granular review, and qualitative insights from over 200 semi-structured interviews including social network/map/photo elicitation methods, and two subsequent sets of remote participatory research workshops. Separate stakeholder co-creation meetings, running through the study, will develop analyses and outputs. Our longitudinal study design enables us to explore significant relationships between variables in the survey data we collect, and also changes in variables with time, including consideration of varying pandemic contexts. The qualitative data will provide more granular detail. We will take a strengths and assets-based approach, underpinned by the social model of disability and by intersectional considerations, to challenge discrimination. Our exploration of the social determinants of health and wellbeing is framed by the social ecological model. RESULTS: The CICADA project was funded by the Health and Social Care Delivery Research (HSDR) Programme of the National Institute for Health and Care Research (NIHR) in March 2021 and began in May 2021. Further work within the project (84 interviews) was commissioned in March 2022, focussing on mental health specifically in North-East England, Greater Manchester and the North-West Coast. Data collection began in August 2021, with the last participants due to be recruited in September 2022. As of January 2022, 5,792 survey respondents and 227 interviewees had provided data. From April 2022, the time of article submission, we will recruit participants for the sub-study and wave 2 of the surveys and qualitative work. We expect results to be published by winter 2022. CONCLUSIONS: In studying the experiences of disabled people with impairments and those living with chronic conditions who come from certain minoritised ethnic groups, we are aiming for transformative research to improve their health and wellbeing. CLINICALTRIAL: INTERNATIONAL REGISTERED REPORT: DERR1-10.2196/38361

APOE4 genotype exerts greater benefit in lowering plasma cholesterol and apolipoprotein B than wild type (E3/E3), after replacement of dietary saturated fats with low glycaemic index carbohydrates

We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial ('RISCK' study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC -0.28 mmol/L p = 0.03; apo B -0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates

Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function

We assessed differences in mitochondrial function in gluteal (gSAT) and abdominal subcutaneous adipose tissue (aSAT) at baseline and in response to 12-weeks of exercise training; and examined depot-specific associations with body fat distribution and insulin sensitivity (S-I). Obese, black South African women (n = 45) were randomized into exercise (n = 23) or control (n = 22) groups. Exercise group completed 12-weeks of aerobic and resistance training (n = 20), while the control group (n = 15) continued usual behaviours. Mitochondrial function (high-resolution respirometry and fluorometry) in gSAT and aSAT, SI (frequently sampled intravenous glucose tolerance test), body composition (dual-energy X-ray absorptiometry), and ectopic fat (MRI) were assessed pre- and post-intervention. At baseline, gSAT had higher mitochondrial respiratory capacity and hydrogen peroxide (H2O2) production than aSAT (p &lt; 0.05). Higher gSAT respiration was associated with higher gynoid fat (p &lt; 0.05). Higher gSAT H2O2 production and lower aSAT mitochondrial respiration were independently associated with lower SI (p &lt; 0.05). In response to training, S-I improved and gynoid fat decreased (p &lt; 0.05), while H2O2 production reduced in both depots, and mtDNA decreased in gSAT (p &lt; 0.05). Mitochondrial respiration increased in aSAT and correlated with a decrease in body fat and an increase in soleus and hepatic fat content (p &lt; 0.05). This study highlights the importance of understanding the differences in mitochondrial function in multiple SAT depots when investigating the pathophysiology of insulin resistance and associated risk factors such as body fat distribution and ectopic lipid deposition. Furthermore, we highlight the benefits of exercise training in stimulating positive adaptations in mitochondrial function in gluteal and abdominal SAT depots

Effect of a behavioural intervention in obese pregnant women (the UPBEAT study):a multicentre, randomised controlled trial

BACKGROUND: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants.METHODS: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ?30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (?90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing.FINDINGS: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (?5th customised birthweight centile; 6% vs 5%) did not differ between groups.INTERPRETATION: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants.<br/

Up-regulation of the ATP-binding cassette transporter A1 inhibits hepatitis C virus infection.

International audienceHepatitis C virus (HCV) establishes infection using host lipid metabolism pathways that are thus considered potential targets for indirect anti-HCV strategies. HCV enters the cell via clathrin-dependent endocytosis, interacting with several receptors, and virus-cell fusion, which depends on acidic pH and the integrity of cholesterol-rich domains of the hepatocyte membrane. The ATP-binding Cassette Transporter A1 (ABCA1) mediates cholesterol efflux from hepatocytes to extracellular Apolipoprotein A1 and moves cholesterol within cell membranes. Furthermore, it generates high-density lipoprotein (HDL) particles. HDL protects against arteriosclerosis and cardiovascular disease. We show that the up-regulation of ABCA1 gene expression and its cholesterol efflux function in Huh7.5 hepatoma cells, using the liver X receptor (LXR) agonist GW3965, impairs HCV infection and decreases levels of virus produced. ABCA1-stimulation inhibited HCV cell entry, acting on virus-host cell fusion, but had no impact on virus attachment, replication, or assembly/secretion. It did not affect infectivity or properties of virus particles produced. Silencing of the ABCA1 gene and reduction of the specific cholesterol efflux function counteracted the inhibitory effect of the GW3965 on HCV infection, providing evidence for a key role of ABCA1 in this process. Impaired virus-cell entry correlated with the reorganisation of cholesterol-rich membrane microdomains (lipid rafts). The inhibitory effect could be reversed by an exogenous cholesterol supply, indicating that restriction of HCV infection was induced by changes of cholesterol content/distribution in membrane regions essential for virus-cell fusion. Stimulation of ABCA1 expression by GW3965 inhibited HCV infection of both human primary hepatocytes and isolated human liver slices. This study reveals that pharmacological stimulation of the ABCA1-dependent cholesterol efflux pathway disrupts membrane cholesterol homeostasis, leading to the inhibition of virus-cell fusion and thus HCV cell entry. Therefore besides other beneficial roles, ABCA1 might represent a potential target for HCV therapy