Background Left ventricular diastolic function as assessed by tissue Doppler echocardiography predicts cardiovascular event rates at 4 years of follow-up in patients with hypertension. Our aim was to evaluate whether this extends to predicting cardiovascular mortality after 20 years of follow-up.Methods Conventional (E) and tissue Doppler (e′) echocardiography was performed on hypertensive participants in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) with long-term follow-up ascertained via linkage to the Office of National Statistics. Cardiovascular mortality was defined as death from coronary heart disease, stroke and other cardiovascular aetiology such as heart failure or peripheral vascular disease. Unadjusted and adjusted Cox regression survival models were constructed to investigate the association between tissue Doppler echocardiography measurements and long-term cardiovascular mortality.Results Among 506 hypertensive patients (median age 64, interquartile range (58, 69), 87% male), there were 200 (40%) deaths over a 20-year follow-up period. 60 deaths (12%) were cardiovascular-related.A reduction in e′ was independently associated with increased cardiovascular mortality, after adjusting for the ACC/AHA Atherosclerotic Cardiovascular Disease (ASCVD) risk score, with an inverse HR of 1.22 per 1 cm/s decrease (95% CI 1.04–1.43). A higher E/e′ ratio was independently associated with increased cardiovascular mortality, after adjusting for the ASCVD risk score, with an HR of 1.12 per 1-unit increase (95% CI, 1.02 to 1.23).Conclusions Impaired left ventricular diastolic function, measured using tissue Doppler echocardiography through e′ and E/e′, independently predicts increased cardiovascular mortality over 20 years in hypertensive patients, highlighting its long-term prognostic significance.

The health benefits of the long-chain omega-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been known for over 50 years and underpin the UK population recommendation to consume >450 mg EPA + DHA per day. These recommendations, last revised in 2004, are based mainly on epidemiological evidence. Much research has been conducted in the interim. Most randomised controlled trials (RCT) use doses of EPA + DHA of 840 mg/d or more. For anti-inflammatory, triacylglycerol-lowering and anti-hypertensive effects, >1.5 g EPA + DHA per day is needed. Cognitive benefits are also likely to require these higher intakes. Farmed salmon now contains considerably less EPA + DHA relative to farmed fish of 20 years ago, meaning one portion per week will no longer provide the equivalent of 450 mg EPA + DHA per day. Oily fish alone can only provide a fraction of the EPA + DHA required to meet global needs. Furthermore, there is low global oily fish consumption, with typical intakes of <200 mg EPA + DHA per day, and limited intakes in vegans and vegetarians. Therefore, there is an urgent need for affordable, acceptable, alternative EPA + DHA sources, including vegan/vegetarian friendly options, such as bio-enriched poultry, red meat and milk products; fortified foods; enriched oilseeds (for example, genetically modified Camelina sativa); algae and algal oils; and approaches which enhance endogenous EPA/DHA synthesis. In this narrative review, we suggest that current EPA + DHA intake recommendations are too low, consider EPA/DHA from a holistic health-sustainability perspective and identify research, policy and knowledge mobilisation areas which need attention.

The world, in 2024, faces both climate and biodiversity crises, and the food system does contribute significantly to these crises. For some, the solution is simple - intakes of animal source foods (ASFs) should be considerably reduced, and consumption of plant-source foods (PSFs) should be greatly increased. Advocates for such a dietary transformation express confidence that plant-based diets will not only benefit planetary health, but will provide nutrient adequacy for all, and will also result in considerable protection from chronic non-communicable diseases (NCDs). However, as described in this perspective, the dramatic reductions in ASFs, entailed by many plant-based diets, will worsen already prevalent micronutrient and protein deficiencies. The protections provided by plant-based diets against NCDs appear to be more strongly associated with reduced intakes of calories and salt, and increased intakes of fruit, vegetables, nuts and whole grains, rather than with reduced intakes of ASFs. Any possible absolute adverse effects of red and processed meat consumption on NCDs are very small and uncertain. Other ASFs either appear to have no impact on NCDs (poultry meat and eggs), or are associated with protections against obesity, cardiovascular events, brain disorders and some cancers (seafood and dairy). Rigorous randomized controlled trials of all newly proposed environmentally-protective plant-based diets are required, so as to provide clear-cut evidence of micronutrient and protein adequacy, with or without, supplementation, fortification and/or biofortification. In the meantime, dietary guidelines should advise moderating excessive consumption, rather than substantially limiting or excluding ASFs from the human diet.

Many recent very influential reports, including those from the Global Burden of Disease (GBD) Risk Factor Collaborators, the EAT-Lancet Commission on Food, Planet, Health, and the Lancet Countdown on Health and Climate Change, have recommended dramatic reductions or total exclusion of animal-source foods, particularly ruminant products (red meat and dairy), from the human diet. They strongly suggest that these dietary shifts will not only benefit planetary health but also human health. However, as detailed in this perspective, there are grounds for considerable concern in regard to the quality and transparency of the input data, the validity of the assumptions, and the appropriateness of the statistical modelling, used in the calculation of the global health estimates, which underpin the claimed human health benefits. The lessor bioavailability of protein and key micronutrients from plant-source foods versus animal-source foods was not adequately recognised nor addressed in any of these reports. Furthermore, assessments of bias and certainty were either limited or absent. Despite many of these errors and limitations being publically acknowledged by the GBD and the EAT-Lancet authors, no corrections have been applied to the published papers. As a consequence, these reports continue to erroneously influence food policy decisions and international dietary guidelines, such as the World Wildlife Fund’s Livewell Diet, and the Nordic Nutrition Recommendations 2023.

Abstract Problem The Climate & Health Alliance (CHA) is a coalition of medical, health and advocacy organisations that seeks to highlight the significant health co-benefits of addressing the climate crisis. Our global food system contributes to diet-related chronic disease and has resulted in climate change, pollution, biodiversity collapse and nature loss. A healthy sustainable food system is needed to minimise interrelated obesity, climate change and malnutrition pandemics. Description of the problem The CHA conducted an extensive literature review to: 1. Demonstrate the need for a food system transition ; 2. Identify Ireland's challenge areas ; 3. Make recommendations for a healthy sustainable diet in the Irish context; 4. Recommend policy-level actions for Ireland. The CHA launched ‘Fixing Food Together’ in May 2023. We identified six challenge areas for Ireland: 1. Ending the junk food cycle; 2. Promoting transition to a more plant-based diet; 3. Harnessing the power of international and national guidelines; 4. Reducing food waste; 5. Improving agricultural practices and land use; 6. Using policy to affect behaviour change. Results The CHA presented individual-level recommendations for future Irish dietary guidelines, including breastfeeding, ultra-processed foods, protein foods and food waste. Seven policy recommendations were made: 1. National guidelines; 2. Regulations/laws; 3. Research, processing and technology actions; 4. Financial actions ; 5. Agricultural actions; 6. Public institution actions; 7. Public awareness actions Lessons ‘Fixing Food Together’ represents the first time a healthy sustainable diet and food system has been defined for an Irish context. The cross-sectional nature of the alliance provides a valuable consensus from its member organisations. It brings an often missing public health perspective to the climate and food systems dialogue. Key messages • Our current food system is harming human and planetary health. • ‘Fixing Food Together’ identifies Ireland’s challenge areas and makes recommendations to transition to a healthy sustainable food system.

We wish to compliment the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) Collaborators for their important contributions to global health metrics over the past 30 years. Their standardised and comprehen-sive estimates of the global burden of diseases, injuries, and risk factors have been used by researchers, govern-ment officials, and non-governmental organisations to make comparisons among populations, to track changes over time, and to monitor progress towards key policy targets, such as the Sustainable Development Goals.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Abstract Background We have previously shown that tissue Doppler assessments of left ventricular (LV) diastolic function predict cardiac events in a hypertensive population over a period of 4 years (1). These out-performed traditional echocardiographic measures in a well-treated hypertensive population. Purpose We aimed to test whether tissue Doppler assessment of LV diastolic function would predict cardiovascular (CV) mortality in the Hypertension Associated Cardiovascular Disease sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Methods ASCOT was a multicentre randomised trial with a 2x2 factorial design (2). Inclusion criteria for the study included hypertension and three other CV risk factors, including male sex and age over 55. Protocols, including for echocardiography, have been detailed previously (2, 3). This study comprised the 519 patients recruited to the St Mary's Hospital site of the ASCOT study, who were followed for 19 years with mortality flagged by the Office for National Statistics. We have used all reported deaths on or before 31st January 2019. CV deaths include deaths due to coronary heart disease (CHD), stroke and other CV causes. Echocardiography was performed one year after blood pressure control. mean tissue Doppler E' was calculated as the average of septal, lateral and inferior wall measurements over three cycles. The ratio of the transmitral Doppler E wave velocity and the composite mean of E' was used to calculate E/E' ratio. Statistical analysis was performed using Python including multivariable Cox proportional hazards regression. A two-sided P-value <0.05 was considered statistically significant. Results After a median of 19 years, 317 patients survived (mean age at baseline 60.7y, 38 female) and 202 did not (mean age 68.1y, 30 female). Twenty-three deaths were due to CHD, 11 were due to stroke, 27 were due to other CV causes, and 76 were due to cancer. Baseline characteristics were not significantly different between those who survived to follow up and those who did not. Unadjusted analysis showed a strong association between CV mortality and E' (HR=0.74, p<0.005) and E/E' (HR=1.18, p<0.005) (Table 1). The association between CV mortality and E' was attenuated slightly but persisted after adjusting for age and sex (HR=0.83, p=0.02) and after adjusting for age, sex and systolic BP (HR=0.83, p=0.03). The association between CV mortality and E/E' was attenuated but persisted after adjusting for age and sex (HR=1.12, p=0.01) and after adjusting for age, sex and systolic BP (HR=1.11, p=0.04). There was a weak association between all-cause mortality and both E/E' and E', which was null after adjusting for age and sex. Figure 1 shows unadjusted Kaplan Meier survival curves for E'. Conclusions Tissue Doppler E' velocity and E/E' predicted 19-year cardiovascular mortality in a hypertensive population independent of age, sex and systolic blood pressure. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The HACVD substudy was supported by an investigational grant by Pfizer International, New York, NY, USA. The principal funding source for ASCOT was Pfizer, New York, NY, USA, additional funding was also provided by Servier Research Group, Paris, France, and Leo Laboratories, Copenhagen, Denmark.

Diets low in seafood omega-3 polyunsaturated fatty acids (PUFAs) are very prevalent. Such diets have recently been ranked as the sixth most important dietary risk factor—1.5 million deaths and 33 million disability-adjusted life-years worldwide are attributable to this deficiency. Wild oily fish stocks are insufficient to feed the world’s population, and levels of eicosapentaenoic acid and docosahexaenoic acid (DHA) in farmed fish have more than halved in the last 20 years. Here we report on a double-blinded, controlled trial, where 161 healthy normotensive adults were randomly allocated to eat at least three portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least three omega-3-PUFA enriched (or control) eggs/week, for 6 months. We show that regular consumption of omega-3-PUFA enriched chicken-meat and eggs significantly increased the primary outcome, the red cell omega-3 index (mean difference [98.75% confidence interval] from the group that ate both control foods, 1.7% [0.7, 2.6]). Numbers of subjects with a very high-risk omega-3 index (index < 4%) were more than halved amongst the group that ate both enriched foods. Furthermore, eating the enriched foods resulted in clinically relevant reductions in diastolic blood pressure (− 3.1 mmHg [− 5.8, − 0.3]). We conclude that chicken-meat and eggs, naturally enriched with algae-sourced omega-3-PUFAs, may serve as alternative dietary sources of these essential micronutrients. Unlike many lifestyle interventions, long-term population health benefits do not depend on willingness of individuals to make long-lasting difficult dietary changes, but on the availability of a range of commonly eaten, relatively inexpensive, omega-3-PUFA enriched foods.

AbstractGreater consumption of oily fish, and elevated plasma levels of the long-chain marine-derived omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been strongly and consistently associated with a reduced incidence of heart attacks, strokes, cognitive decline, Alzheimer's disease and cancers. Despite international guidelines recommending eating oily fish at least once per week (> 250mg/day DHA and EPA), many people do not eat fish, and only a small minority of the world's population have optimal omega-3-PUFA plasma and tissue levels. Hence, in this project, we studied the bioavailability and blood pressure lowering effects of recently developed alternatives to oily fish, namely chicken-meat and eggs naturally enriched with algae-sourced omega-3-PUFAs.This was a double-blinded, controlled, randomised trial. Using a 2X2 factorial design, 161 healthy participants were randomized to eat at least 3 portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least 3 omega-3-PUFA enriched (or control) eggs/week, for 6 months.Compared to control foods, eating enriched eggs, enriched chicken-meat and the combination for 6 months, resulted in plasma EPA increments (μg/g) of 3.1[2.8], 8.8[2.9]* & 4.7[2.9], plasma DHA increments (μg/g) of 5.1[3.7], 9.3[3.8]* & 13.1[3.9]*, and omega-3-index (sum of EPA + DHA as a percentage of total fatty acids in erythrocytes, %) increments of 0.9[0.3]*, 0.7[0.4]* & 1.5[0.4]*, respectively. Mean 24-hour ambulatory blood pressure (systolic/diastolic, mmHg) declined with the enriched foods 0.3[1.3]/-0.2[1.0], -0.7[1.4]/-1.4[1.0], & -1.9[1.4]/-2.9[1.0]*, respectively. Data provided as mean difference[SEM], and * denotes p < 0.05.Regular consumption of omega-3-PUFA enriched chicken-meat and eggs resulted in statistically significant and clinically relevant increases in plasma and red cell levels of DHA and EPA. Both plasma and red cell bioavailability were similar to those previously described for oily fish. Furthermore, blood pressure, an important biomarker of cardiovascular health, decreased in those eating the omega-3-PUFA enriched foods. Omega-3-PUFA enriched chicken-meat and eggs offers consumers an attractive additional alternative to eating oily fish. Unlike many lifestyle interventions, long-term large population health benefits are not dependent on willingness of people to make long-lasting dietary changes, but on the widespread availability of a range of inexpensive, commonly eaten, naturally enriched foods.

BACKGROUND:Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions. OBJECTIVES:This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population. METHODS:Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs. RESULTS:Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals. CONCLUSIONS:The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients ( F ROH ) for >1.4 million individuals, we show that F ROH is significantly associated ( p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of F ROH are confirmed within full-sibling pairs, where the variation in F ROH is independent of all environmental confounding.

IntroductionThe association between long-chain omega-3 polyunsaturated fatty acids (PUFAs), brain health, cognitive function and mood has been the subject of intensive research. Marine-derived omega-3 PUFAs, such as docosahexaenoic acid and eicosapentaenoic acid, are highly concentrated in neuronal membranes and affect brain function. Many studies have found that consumption of omega-3 PUFAs is associated with lower risk of cognitive or mood dysfunction. However, other studies have demonstrated no beneficial effects. There appears to be inconsistent findings from both epidemiological and randomised controlled trial (RCT) studies. The aim of this review is to compile the previous literature and establish the efficacy of omega-3 PUFAs in enhancing cognitive performance and mood in healthy adults.Methods and analysisProspective cohort studies, RCTs, controlled clinical trials, controlled before and after studies, interrupted time series with a minimum of 3 months duration will be eligible for inclusion. Studies on healthy adults over the age of 18, where the intervention/exposure of interest is omega-3 PUFAs will be included. The outcomes of interest are cognition and mood. Studies will be eligible for inclusion if they measure changes in cognitive function or mood, or the risk of developing cognitive or mood disorders using validated tools and assessments. Relevant search terms and keywords will be used to generate a systematic search in Cochrane Library, MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus and the grey literature. Two independent reviewers will screen studies for eligibility. Risk of bias in cohort and non-randomised studies will be assessed using the ROBINS-I tool. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials will be used for RCTs. If there are sufficient data, a meta-analysis will be conducted.Ethics and disseminationThis systematic review does not involve primary data collection and therefore formal ethical approval is not required. Results will be disseminated through peer reviewed publications, conference presentations and the popular press.PROSPERO registration numberCRD42018080800.

The increased cardiovascular mortality in acromegaly can be reversed by achieving plasma GH concentrations to a target of <2ng/ml and normalizing IGF-1 concentrations to within the age-related reference range. However, in approximately 30% of patients, plasma GH concentrations which are on target are associated with discordantly elevated plasma IGF-1 concentrations. It is not known whether this discordance confers excess morbidity. The aim of this study was to determine whether discordance of plasma GH and IGF-1 negatively affects parameters which predict cardiovascular morbidity. Methods: Group 1 (Concordant): 28 patients (15F,13M) with plasma GH <2ng/ml and IGF-1 concentrations within the age and sex matched reference range. Group 2 (Discordant): 27 patients (5F, 22M) with plasma GH <2ng/ml and elevated plasma IGF-1 concentrations above the age and sex-matched reference range. IGF-1 and GH concentrations were analysed in one laboratory using IDS-iSYS assay. Patients were excluded if they were receiving Pegvisomant therapy, if they had a change in therapy in the preceding 6 months or if the random GH was >2ng/ml. Parameters Measured: OGTT with GH, fasting lipid profile, HOMA-IR, Carotid Intima Thickness (CIMT), pulse wave velocity (PWV), flow mediated dilatation (FMD) and 24-hour ambulatory blood pressure. All tests were completed with a standardised protocol over one day. IGF-1 concentrations were calculated as % Upper limit of normal (%ULN) to allow comparison across different age matched reference ranges. Results: The median age (range) was similar in the two groups; 54 (32-78) years in the concordant group and 61 (34-83) years in the discordant group, p=0.45. There were no significant between group differences in BMI, smoking, hypertension, diabetes mellitus or obstructive sleep apnoea. GH nadir during OGTT (p=0.03) and basal plasma GH (p=0.03) were higher in the discordant group. HOMA-IR was also higher in the discordant group (median = 1.75, range 0.73 - 4.88) compared to the concordant group (median = 1.123, range 0.27-4.63), p=0.01. However, there were no significant differences in HbA1c and fasting glucose between the two groups. Furthermore, there were no significant differences between IMT (p=0.63), PWV (p=0.3), mean daytime (p=0.48) or night-time systolic blood pressure (p=0.54) between the two groups. Conclusion: Elevated plasma IGF-1, with controlled GH concentrations, was associated with higher basal GH, higher nadir GH on OGTT and higher markers of insulin resistance in comparison to patients with controlled GH and IGF-1 concentrations. However, we found no difference in other predictors of future cardiovascular risk between the two groups. Further investigation of these findings is warranted to determine if the differences in HOMA-IR and GH dynamics between the two groups requires intervention.

Objective Evaluate the feasibility and acceptability of routine aspirin in low-risk women, compared with screening-test indicated aspirin for the prevention of pre-eclampsia and fetal growth restriction. Design Multicentre open-label feasibility randomised controlled trial. Setting Two tertiary maternity hospitals in Dublin, Ireland. Participants 546 low-risk nulliparous women completed the study. Interventions Women underwent computerised randomisation to: Group 1-routine aspirin 75 mg from 11 until 36 weeks; Group 2-no aspirin and; Group 3-aspirin based on the Fetal Medicine Foundation screening test. Primary and secondary outcome measures (1) Proportion agreeing to participate; (2) compliance with protocol; (3) proportion where first trimester uterine artery Doppler was obtainable and; (4) time taken to issue a screening result. Secondary outcomes included rates of pre-eclampsia and small-for-gestational-age fetuses. Results 546 were included in the routine aspirin (n=179), no aspirin (n=183) and screen and treat (n=184) groups. 546 of 1054 were approached (51.8%) and enrolled. Average aspirin adherence was 90%. The uterine artery Doppler was obtained in 98.4% (181/184) and the average time to obtain a screening result was 7.6 (0-26) days. Of those taking aspirin, vaginal spotting was greater; n=29 (15.1%), non-aspirin n=28 (7.9%), OR 2.1 (95% CI 1.2 to 3.6). Postpartum haemorrhage >500 mL was also greater; aspirin n=26 (13.5%), no aspirin n=20 (5.6%), OR 2.6 (95% CI 1.4 to 4.8). Conclusion Low-risk nulliparous women are open to taking aspirin in pregnancy and had high levels of adherence. Aspirin use was associated with greater rates of vaginal bleeding. An appropriately powered randomised controlled trial is now required to address the efficacy and safety of universal low-dose aspirin in low-risk pregnancy compared with a screening approach.

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