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Kallis C, Kaura A, Samuel N, et al., 2023, The Relationship Between Cardiac Troponin in Hospitalised Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients With Major Adverse Cardiac Events (MACE) and COPD Readmissions, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Hahn J, Bressler J, Domingo-Relloso A, et al., 2023, DNA methylation analysis is used to identify novel genetic loci associated with circulating fibrinogen levels in blood, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 21, Pages: 1135-1147, ISSN: 1538-7933
Yin X, Paige E, Tian M, et al., 2023, The proportion of dietary salt replaced with potassium-enriched salt in the SSaSS: implications for scale-up, Hypertension, Vol: 80, Pages: 956-965, ISSN: 0194-911X
BACKGROUND: The SSaSS (Salt Substitute and Stroke Study) recently reported definitive effects of a potassium-enriched salt on cardiovascular outcomes and death. Quantifying the amount of potassium-enriched salt used by trial participants is important for understanding the magnitude of the effect of potassium-enriched salt on risk reduction and how population-wide scale-up might be achieved. METHODS: Baseline and annual 24-hour urine samples were collected from subgroups of participants in SSaSS throughout the 5-year follow-up. The mean difference in 24-hour potassium excretion between the 2 groups was used to estimate the quantity of potassium-enriched salt consumed in the intervention group. The corresponding projected difference in sodium intake between groups was calculated and compared with the observed difference. RESULTS: The potassium-enriched salt group, compared to the regular salt group, had a mean increase in 24-hour urinary potassium excretion of 0.80 g/d (95% CI, 0.71-0.90), which equates to consumption of 8.8 g/d (95% CI, 7.8-9.9) of potassium-enriched salt. Based on 8.8 g/d potassium-enriched salt consumption, the projected difference in 24-hour urinary sodium excretion was -0.79 g/d. This compares to an observed difference of -0.35 g/d (95% CI, -0.55 to -0.15) and suggests that 72% of baseline regular salt intake was replaced by potassium-enriched salt. CONCLUSIONS: The smaller than anticipated between-group difference in sodium excretion likely results from the joint use of regular salt and potassium-enriched salt in the intervention group. Our findings suggest that even an incomplete replacement of regular salt with potassium-enriched salt can deliver significant health gains. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02092090.
Yuan Y, Jin A, Neal B, et al., 2023, Salt substitution and salt-supply restriction for lowering blood pressure in elderly care facilities: a cluster-randomized trial, Nature Medicine, Vol: 29, Pages: 973-981, ISSN: 1078-8956
There is a paucity of high-quality evidence on the effectiveness and safety of salt reduction strategies, particularly for older people, who have the most to benefit but are at higher risk of adverse effects. Here, we conducted a clinical trial in which 48 residential elderly care facilities in China (1,612 participants including 1,230 men and 382 women, 55 years or older) were cluster-randomized using a 2 × 2 factorial design to provision of salt substitute (62.5% NaCl and 25% KCl) versus usual salt and to a progressively restricted versus usual supply of salt or salt substitute for 2 years. Salt substitute compared with usual salt lowered systolic blood pressure (-7.1 mmHg, 95% confidence interval (CI) -10.5 to -3.8), meeting the primary outcome of the trial, whereas restricted supply compared with usual supply of salt or salt substitute had no effect on systolic blood pressure. Salt substitute also lowered diastolic blood pressure (-1.9 mmHg, 95% CI -3.6 to -0.2) and resulted in fewer cardiovascular events (hazard ratio (HR) 0.60, 95% CI 0.38-0.96), but had no effect on total mortality (HR 0.84, 95% CI 0.63-1.13). From a safety standpoint, salt substitute increased mean serum potassium and led to more frequent biochemical hyperkalemia, but was not associated with adverse clinical outcomes. In contrast, salt restriction had no effect on any study outcome. The results of this trial indicate that use of salt substitute, but not efforts to restrict salt supply, may achieve blood pressure lowering and deliver health benefits to residents of elderly care facilities in China. Clinicaltrials.gov registration: NCT03290716.
Mina T, Yew YW, Ng HK, et al., 2023, Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study., The Lancet Regional Health. Western Pacific, Vol: 33, Pages: 1-11, ISSN: 2666-6065
BACKGROUND: Obesity and related metabolic disturbances including diabetes, hypertension and hyperlipidemia predict future cognitive decline. Asia has a high prevalence of both obesity and metabolic disease, potentially amplifying the future burden of dementia in the region. We aimed to investigate the impact of adiposity and metabolic risk on cognitive function in Asian populations, using an epidemiological analysis and a two-sample Mendelian Randomization (MR) study. METHODS: The Health for Life in Singapore (HELIOS) Study is a population-based cohort of South-East-Asian men and women in Singapore, aged 30-84 years. We analyzed 8769 participants with metabolic and cognitive data collected between 2018 and 2021. Whole-body fat mass was quantified with Dual X-Ray Absorptiometry (DEXA). Cognition was assessed using a computerized cognitive battery. An index of general cognition ' g ' was derived through factor analysis. We tested the relationship of fat mass indices and metabolic measures with ' g ' using regression approaches. We then performed inverse-variance-weighted MR of adiposity and metabolic risk factors on ' g ', using summary statistics for genome-wide association studies of BMI, visceral adipose tissue (VAT), waist-hip-ratio (WHR), blood pressure, HDL cholesterol, triglycerides, fasting glucose, HbA1c, and general cognition. FINDINGS: Participants were 58.9% female, and aged 51.4 (11.3) years. In univariate analysis, all 29 adiposity and metabolic measures assessed were associated with ' g ' at P < 0.05. In multivariable analyses, reduced ' g ' was consistently associated with increased visceral fat mass index and lower HDL cholesterol (P < 0.001), but not with blood pressure, triglycerides, or glycemic indices. The reduction in ' g ' associated with 1SD higher visceral fat, or 1SD lower HDL cholesterol, was equivalent to a 0.7 and 0.9-year increase in chronological age respectively (P < 0.001). Inverse vari
Ezzati M, Mishra A, Zhou B, et al., 2023, Diminishing benefits of urban living for children and adolescents’ growth and development, Nature, Vol: 615, Pages: 874-883, ISSN: 0028-0836
Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1,2,3,4,5,6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
Routen A, O'Mahoney L, Aiyegbusi OL, et al., 2023, Patient and public involvement within epidemiological studies of long COVID in the UK, NATURE MEDICINE, ISSN: 1078-8956
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Elliott P, Ward H, Riley S, 2023, Population monitoring of SARS-CoV-2 infections via random sampling during the COVID-19 pandemic., American Journal of Public Health, Pages: e1-e3, ISSN: 0090-0036
Elliott P, Whitaker M, Tang D, et al., 2023, Design and implementation of a national SARS-CoV-2 monitoring programme in England: REACT-1 Study, American Journal of Public Health, ISSN: 0090-0036
Data System. The REal-time Assessment of Community Transmission-1 (REACT-1) Study was funded by the Department of Health and Social Care in England to provide reliable and timely estimates of prevalence of SARS-CoV-2 infection by time, person and place.Data Collection/Processing. The data were obtained by writing to named individuals aged 5 years and above in random cross-sections of the population of England, using the National Health Service (NHS) list of patients registered with a general practitioner (>99% coverage) as sampling frame. Data were collected 2-3 weekly approximately every month across 19distinct rounds of data collection from May 1, 2020 to March 31, 2022.Data Analysis/Dissemination. The data and study materials are widely disseminated via the study website, preprints, publications in peer-reviewed journals and the media. Data tabulations suitably anonymised to protect participant confidentiality are available on request to the study’s Data Access Committee.Implications. The study provided inter alia real-time data on SARS-CoV-2 prevalence over time, by area, and by socio-demographic variables; estimates of vaccine effectiveness; symptom profiles and detected emergence of new variants based on viral genome sequencing.
Aljuraiban GS, Gibson R, Chan DSM, et al., 2023, Lifestyle score and risk of hypertension in the airwave health monitoring study of British police force employees, International Journal of Environmental Research and Public Health, Vol: 20, Pages: 1-14, ISSN: 1660-4601
BACKGROUND: Evidence suggest that promoting a combination of healthy lifestyle behaviors instead of exclusively focusing on a single behavior may have a greater impact on blood pressure (BP). We aimed to evaluate lifestyle factors and their impact on the risk of hypertension and BP. METHODS: We analyzed cross-sectional health-screening data from the Airwave Health Monitoring Study of 40,462 British police force staff. A basic lifestyle-score including waist-circumference, smoking and serum total cholesterol was calculated, with a greater value indicating a better lifestyle. Individual/combined scores of other lifestyle factors (sleep duration, physical activity, alcohol intake, and diet quality) were also developed. RESULTS: A 1-point higher basic lifestyle-score was associated with a lower systolic BP (SBP; -2.05 mmHg, 95%CI: -2.15, -1.95); diastolic BP (DBP; -1.98 mmHg, 95%CI: -2.05, -1.91) and was inversely associated with risk of hypertension. Combined scores of other factors showed attenuated but significant associations with the addition of sleep, physical activity, and diet quality to the basic lifestyle-score; however, alcohol intake did not further attenuate results. CONCLUSIONS: Modifiable intermediary factors have a stronger contribution to BP, namely, waist-circumference and cholesterol levels and factors that may directly influence them, such as diet, physical activity and sleep. Observed findings suggest that alcohol is a confounder in the BP-lifestyle score relation.
Dehghan A, Huang J, Hesbani N, et al., 2023, Genome Wide Association Study and Multi-Ancestry MetaAnalysis Identify Common Variants Associated With Carotid Artery Intima Media Thickness, CIRCULATION, Vol: 147, ISSN: 0009-7322
Dib M-J, Meena D, Zagkos L, et al., 2023, Sex-Specific Genetic Interrogation of Cardiovascular Disease Drug Targets, American Heart Association's Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
Dib M-J, Zagkos L, Elliott P, et al., 2023, Associations of Genetically Determined Favourable and Unfavourable Adiposity Across the Phenome, American Heart Association's Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
Huang J, Gill D, Zuber V, et al., 2023, Circulatory proteins relate cardiovascular disease to cognitive performance: a Mendelian randomisation study, Frontiers in Genetics, Vol: 14, Pages: 1-11, ISSN: 1664-8021
Background and objectives: Mechanistic research suggests synergistic effects of cardiovascular disease (CVD) and dementia pathologies on cognitive decline. Interventions targeting proteins relevant to shared mechanisms underlying CVD and dementia could also be used for the prevention of cognitive impairment.Methods: We applied Mendelian randomisation (MR) and colocalization analysis to investigate the causal relationships of 90 CVD-related proteins measured by the Olink CVD I panel with cognitive traits. Genetic instruments for circulatory protein concentrations were obtained using a meta-analysis of genome-wide association studies (GWAS) from the SCALLOP consortium (N = 17,747) based on three sets of criteria: 1) protein quantitative trait loci (pQTL); 2) cis-pQTL (pQTL within ±500 kb from the coding gene); and 3) brain-specific cis-expression QTL (cis-eQTL) which accounts for coding gene expression based on GTEx8. Genetic associations of cognitive performance were obtained from GWAS for either: 1) general cognitive function constructed using Principal Component Analysis (N = 300,486); or, 2) g Factor constructed using genomic structural equation modelling (N = 11,263–331,679). Findings for candidate causal proteins were replicated using a separate protein GWAS in Icelanders (N = 35,559).Results: A higher concentration of genetically predicted circulatory myeloperoxidase (MPO) was nominally associated with better cognitive performance (p < 0.05) using different selection criteria for genetic instruments. Particularly, brain-specific cis-eQTL predicted MPO, which accounts for protein-coding gene expression in brain tissues, was associated with general cognitive function (βWald = 0.22, PWald = 2.4 × 10−4). The posterior probability for colocalization (PP.H4) of MPO pQTL with the g Factor was 0.577. Findings for MPO were replicated using the Icelandic GWAS. Although we did not find evidence for colocalization, we found that higher gene
Atchison C, Moshe M, Brown J, et al., 2023, Validity of self-testing at home with rapid SARS-CoV-2 antibody detection by lateral flow immunoassay, Clinical Infectious Diseases, Vol: 76, Pages: 658-666, ISSN: 1058-4838
Background: We explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow immunoassay (LFIA) performance under field conditions compared to laboratory-based ELISA and live virus neutralisation. Methods: In July 2021, 3758 participants performed, at home, a self-administered LFIA on finger-prick blood, reported and submitted a photograph of the result, and provided a self-collected capillary blood sample for assessment of IgG antibodies using the Roche Elecsys® Anti-SARS-CoV-2 assay. We compared the self-reported LFIA result to the quantitative Roche assay and checked the reading of the LFIA result with an automated image analysis (ALFA). In a subsample of 250 participants, we compared the results to live virus neutralisation. Results: Almost all participants (3593/3758, 95.6%) had been vaccinated or reported prior infection. Overall, 2777/3758 (73.9%) were positive on self-reported LFIA, 2811/3457 (81.3%) positive by LFIA when ALFA-reported, and 3622/3758 (96.4%) positive on Roche (using the manufacturer reference standard threshold for positivity of 0.8 U ml−1). Live virus neutralisation was detected in 169 of 250 randomly selected samples (67.6%); 133/169 were positive with self-reported LFIA (sensitivity 78.7%; 95% CI 71.8, 84.6), 142/155 (91.6%; 86.1, 95.5) with ALFA, and 169 (100%; 97.8, 100.0) with Roche. There were 81 samples with no detectable virus neutralisation; 47/81 were negative with self-reported LFIA (specificity 58.0%; 95% CI 46.5, 68.9), 34/75 (45.3%; 33.8, 57.3) with ALFA, and 0/81 (0%; 0.0, 4.5) with Roche. Conclusions: Self-administered LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ELISA with virus neutralisation.
Kojouri M, Pinto R, Mustafa R, et al., 2023, Metabolome-wide association study on physical activity, Scientific Reports, Vol: 13, Pages: 1-9, ISSN: 2045-2322
The underlying mechanisms linking physical activity to better health are not fully understood. Here we examined the associations between physical activity and small circulatory molecules, the metabolome, to highlight relevant biological pathways. We examined plasma metabolites associated with self-reported physical activity among 2217 participants from the Airwave Health Monitoring Study. Metabolic profiling was conducted using the mass spectrometry-based Metabolon platform (LC/GC–MS), measuring 828 known metabolites. We replicated our findings in an independent subset of the study (n = 2971) using untargeted LC–MS. Mendelian randomisation was carried out to investigate potential causal associations between physical activity, body mass index, and metabolites. Higher vigorous physical activity was associated (P < 0.05/828 = 6.03 × 10–5) with circulatory levels of 28 metabolites adjusted for age, sex and body mass index. The association was inverse for glutamate and diacylglycerol lipids, and direct for 3–4-hydroxyphenyllactate, phenyl lactate (PLA), alpha-hydroxy isovalerate, tiglylcarnitine, alpha-hydroxyisocaproate, 2-hydroxy-3-methylvalerate, isobutyrylcarnitine, imidazole lactate, methionine sulfone, indole lactate, plasmalogen lipids, pristanate and fumarate. In the replication panel, we found 23 untargeted LC–MS features annotated to the identified metabolites, for which we found nominal associations with the same direction of effect for three features annotated to 1-(1-enyl-palmitoyl)-2-oleoyl-GPC (P-16:0/18:1), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2), 1-stearoyl-2-dihomo-linolenoyl-GPC (18:0/20:3n3 or 6). Using Mendelian randomisation, we showed a potential causal relationship between body mass index and three identified metabolites. Circulatory metabolites are associated with physical activity and may play a role in mediating its health effects.
Huang J, Su B, Karhunen V, et al., 2023, Inflammatory diseases, inflammatory biomarkers, and Alzheimer disease: an observational analysis and mendelian randomization, Neurology, Vol: 100, Pages: e568-e581, ISSN: 0028-3878
OBJECTIVES: Whether chronic autoimmune inflammatory diseases causally affect the risk of AD is controversial. We characterised the relationship between inflammatory diseases and the risk of AD and explore the role of circulating inflammatory biomarkers in the relationships between inflammatory diseases and AD. METHODS: We performed observational analyses for chronic autoimmune inflammatory diseases and risk of AD using data from 2,047,513 participants identified in the UK Clinical Practice Research Datalink (CPRD). Using data of a total of more than 1,100,000 individuals from 15 large scale genome-wide association study (GWAS) datasets, we performed two-sample Mendelian randomisation (MR) to investigate the relationships between chronic autoimmune inflammatory diseases, circulating inflammatory biomarker levels, and risk of AD. RESULTS: Cox regression models using CPRD data showed that overall incidence of AD was higher among patients with inflammatory bowel disease (IBD) (hazard ratio (HR)=1.17; 95%CI 1.15 to 1.19; P-value=2.1×10-4), other inflammatory polyarthropathies & systematic connective tissue disorders (OID) (HR=1.13; 95%CI 1.12 to 1.14; P-value=8.6×10-5), psoriasis (HR=1.13; 95%CI 1.10 to 1.16; P-value=2.6×10-4), rheumatoid arthritis (RA) (HR=1.08; 95%CI 1.06 to 1.11; P-value=4.0×10-4), and multiple sclerosis (MS) (HR=1.06; 95%CI 1.04 to 1.07; P-value=2.8×10-4) compared to the age (± 5 years) and sex-matched comparison groups free from all inflammatory diseases under investigation. Bidirectional MR analysis identified relationships between chronic autoimmune inflammatory diseases and circulating inflammatory biomarkers. Particularly, circulating monokine induced by gamma interferon (MIG) level was suggestively associated with a higher risk of AD (odds ratio from inverse variance weighted (ORIVW)=1.23; 95%CI 1.06 to 1.42; PIVW=0.007), and lower risk of Crohn's disease (ORIVW=0.73; 95%CI -0.62, 0.86; PIVW=1.3×10
Eales O, Page AJ, Tang SN, et al., 2023, The use of representative community samples to assess SARS-CoV-2 lineage competition: Alpha outcompetes Beta and wild-type in England from January to March 2021., Microbial Genomics, Vol: 9, Pages: 1-14, ISSN: 2057-5858
Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy and will be a high priority for public health for the foreseeable future. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained using a variety of methods all of which are known to contain biases. As a case study, using an approach which is largely free of biases, we here describe lineage dynamics and phylogenetic relationships of the Alpha and Beta variant in England during the first 3 months of 2021 using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the Alpha variant (first identified in Kent) becoming predominant, driven by a reproduction number 0.3 higher than for the prior wild-type. During January, positive samples were more likely to be Alpha in those aged 18 to 54 years old. Although individuals infected with the Alpha variant were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild-type, they were more likely to be antibody-positive 6 weeks after infection. Further, viral load was higher in those infected with the Alpha variant as measured by cycle threshold (Ct) values. The presence of infections with non-imported Beta variant (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing. These results highlight how sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance during periods of lineage diversity.
Cooper E, Lound A, Atchison CJ, et al., 2023, Awareness and perceptions of Long COVID among people in the REACT programme: early insights from a pilot interview study, PLoS One, Vol: 18, ISSN: 1932-6203
BACKGROUND: Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID. METHODS: People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis. RESULTS: We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID. CONCLUSION: This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation
Al-Jafar R, Wahyuni NS, Belhaj K, et al., 2023, The impact of Ramadan fasting on anthropometric measurements and body composition: evidence from London Ramadan Study and a meta-analysis, Frontiers in Nutrition, Vol: 10, Pages: 1-24, ISSN: 2296-861X
Background: Although the effect of Ramadan intermittent fasting (RIF) on anthropometry and body composition has been questioned, none of the previous studies tried to explain the reported changes in these parameters. Also, systematic reviews that investigated the topic were limited to healthy individuals or a specific disease group.Methods: The London Ramadan Study (LORANS) is an observational study on health effects of RIF. We measured weight, waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-hip ratio (WHR), basal metabolic rate (BMR), fat percentage (FP), free-fat mass (FFM), extremities predicted muscle mass, total body water (TBW), trunk FM, trunk FFM and trunk predicted muscle mass before and immediately after Ramadan. Using mixed-effects regression models, we investigated the effect of RIF with adjustment for potential confounders. We also conducted a meta-analysis of the results of LORANS with other studies that investigated the effect of RIF on anthropometry and body composition. The review protocol is registered with PROSPERO registry (CRD42020186532).Results: We recruited 146 participants (Mean ± SD age = 43.3 ± 15 years). Immediately after Ramadan, compared with before Ramadan, the mean difference was−1.6 kg (P<0.01) in weight,−1.95cm (P<0.01) in WC,−2.86cm (P <0.01) in HC, −0.60 kg/m2 (P < 0.01) in BMI and −1.24 kg (P < 0.01) in FM. In the systematic review and meta-analysis, after screening 2,150 titles and abstracts, 66 studies comprising 7,611 participants were included. In the general population, RIF was followed by a reduction of 1.12 Kg in body weight (−1.89– −0.36, I2 = 0), 0.74 kg/m2 reduction in BMI (−0.96– −0.53, I2 = 0), 1.54cm reduction in WC (−2.37– −0.71, I2 = 0) and 1.76cm reduction in HC (−2.69– −0.83, I2 = 0). The effect of fasting on anthropometric and body composition parame
Elliott J, Bodinier B, Whitaker M, et al., 2023, Improving cardiovascular risk prediction beyond pooled cohort equations: a prospective cohort of 304,356 participants
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Pooled Cohort Equations (PCE) are used to predict cardiovascular disease (CVD) risk. Inclusion of other variables may improve risk prediction.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>Identify variables improving CVD risk prediction beyond recalibrated PCE.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Prospective cohort study; sex-stratified Cox survival models with LASSO stability selection to predict CVD in non-overlapping subsets: variable selection (40%), model training (30%) and testing (30%).</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>UK population.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>UK Biobank: 121,724 and 182,632 healthy men and women, respectively, aged 38-73 years at baseline.</jats:p></jats:sec><jats:sec><jats:title>Measurements</jats:title><jats:p>Personal/family medical history; lifestyle factors; genetic, biochemical, hematological, and metabolomic blood markers. Outcomes were incident hospitalization or mortality from CVD.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>There were 11,899 (men) and 9,110 (women) incident CVD cases with median 12.1 years follow-up. Variables selected for both men and women were: age, albumin, antihypertensive medication, apolipoprotein B, atrial fibrillation, C-reactive protein, current smoker, cystatin C, family history of coronary artery disease, glycated hemoglobin, polygenic risk score (PRS) for CVD and systolic blood pressure. Also selected: apolipoprotein A1, lipoprotein(a), white blood cell count, deprivation index (men); triglycerides (women).
Elliott P, 2023, NUTRITION, CARDIO-METABOLIC RISK AND THE METABOLOME, 29th Scientific Meeting of the International Society of Hypertension (ISH), Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E108-E108, ISSN: 0263-6352
Garcia-Segura ME, Durainayagam BR, Liggi S, et al., 2023, Pathway-based integration of multi-omics data reveals lipidomics alterations validated in an Alzheimer´s Disease mouse model and risk loci carriers, Journal of Neurochemistry, Vol: 164, Pages: 57-76, ISSN: 0022-3042
Alzheimer´s Disease (AD) is a highly prevalent neurodegenerative disorder. Despite increasing evidence of the importance of metabolic dysregulation in AD, the underlying metabolic changes that may impact amyloid plaque formation are not understood, particularly for late onset AD. This study analyzed genome-wide association studies (GWAS), transcriptomics and proteomics data obtained from several data repositories to obtain differentially expressed (DE) multi-omics elements in mouse models of AD. We characterized the metabolic modulation in these datasets using gene ontology, transcription factor, pathway, and cell-type enrichment analyses. A predicted lipid signature was extracted from genome-scale metabolic networks (GSMN) and subsequently validated in a lipidomic dataset derived from cortical tissue of ABCA-7 null mice, a mouse model of one of the genes associated with late onset AD. Moreover, a metabolome-wide association study (MWAS) was performed to further characterize the association between dysregulated lipid metabolism in human blood serum and genes associated with AD risk. We found 203 DE transcripts, 164 DE proteins and 58 DE GWAS-derived mouse orthologs associated with significantly enriched metabolic biological processes. Lipid and bioenergetics metabolic pathways were significantly over-represented across the AD multi-omics datasets. Microglia and astrocytes were significantly enriched in the lipid-predominant AD-metabolic transcriptome. We also extracted a predicted lipid signature that was validated and robustly modelled class separation in the ABCA7 mice cortical lipidome, with 11 of these lipid species exhibiting statistically significant modulations. MWAS revealed 298 AD single nucleotide polymorphisms (SNP)-metabolite associations, of which 70% corresponded to lipid classes. These results support the importance of lipid metabolism dysregulation in AD and highlight the suitability of mapping AD multi-omics data into GSMNs to identify metabol
Posma JM, Perez IG, Karaman I, et al., 2023, Host genomic influence on the gut microbial metabolite-blood pressure relationship, 29th Scientific Meeting of the International Society of Hypertension (Hypertension Kyoto 2022), Publisher: Lippincott, Williams & Wilkins, Pages: E240-E240, ISSN: 0263-6352
Miyagawa N, Sekikawa A, Miura K, et al., 2023, Circulating plasma phospholipid fatty acid levels as a biomarker of habitual dietary fat intake: The INTERMAP/INTERLIPID Study, JOURNAL OF CLINICAL LIPIDOLOGY, Vol: 17, Pages: 131-141, ISSN: 1933-2874
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- Citations: 1
Zagkos L, Dib M-J, Pinto R, et al., 2022, Associations of genetically predicted fatty acid levels across the phenome: a mendelian randomisation study, PLoS Medicine, Vol: 19, ISSN: 1549-1277
BACKGROUND: Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes. METHODS AND FINDINGS: The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.
Kanagasabai T, Carter E, Yan L, et al., 2022, Cross-sectional study of household solid fuel use and renal function in older adults in China, Environmental Research, Vol: 219, Pages: 1-11, ISSN: 0013-9351
BackgroundEmerging evidence links outdoor air pollution and declined renal function but the relationship between household air pollution and renal function is not well understood.MethodsUsing cross-sectional data from the multi-provincial INTERMAP-China Prospective Study, we collected blood samples and questionnaire information on stove use and socio-demographic factors. We calculated estimated glomerular filtration rate (eGFR) from serum creatinine to assess renal function. Participants with eGFR <60 mL/min per 1.73 m2 were defined as having chronic kidney disease (CKD) in this analysis. Generalized estimating equations were used to estimate the association of household fuel with renal function and prevalent CKD in models adjusting for confounders.ResultsAmong the 646 enrolled adults (40-79y; 56% female), one-third exclusively used clean fuel (gas and electric) cookstoves and 11% of northern China participants (n = 49 of 434) used only clean fuel heaters, whereas the rest used solid fuel. In multivariable models, use of solid fuel cookstoves was associated with 0.17 ml/min/1.73 m2 (95% CI: −0.30, 0.64) higher eGFR and 19% (0.86, 1.64) higher prevalence of CKD than exclusive clean fuel use. Greater intensity of solid fuel use was associated with 0.25 ml/min/1.73 m2 (−0.71, 0.21) lower eGFR per 5 stove-use years, though the confidence intervals included the null, while greater current intensity of indoor solid fuel use was associated with 1.02 (1.00, 1.04) higher prevalent CKD per 100 stove-use days per year. Larger associations between current solid fuel use and intensity of use with lower eGFR and prevalent CKD were observed among participants in southern China, those with hypertension or diabetes (eGFR only), and females (CKD only), through these groups had small sample sizes and some confidence intervals included the null.ConclusionWe found inconsistent evidence associating household solid fuel use and renal function in this cross-sectional study o
Leong W-Y, Gupta A, Hasan M, et al., 2022, Reference equations for evaluation of spirometry function tests in South Asia, and amongst South Asians living in other countries, European Respiratory Journal, Vol: 60, ISSN: 0903-1936
Background:There is little data to accurate interpretation of spirometry data in SouthAsia, a major global region with high reported burden for chronicrespiratory disease.Method:We measured lung function in 7,453 healthy men and women aged over18 years, from Bangladesh, North India, South India, Pakistan and SriLanka, as part of the South Asia Biobank study. We first assessed theaccuracy of existing equations for predicting normal forced vital capacity(FVC), forced expiratory volume in 1s (FEV1), and FEV1/FVC ratio. Wethen used our data to derive (N=5,589) and internally validate(N=1,864) new prediction equations amongst South Asians, with furtherexternal validation amongst 339 healthy South Asians living inSingapore.Results:GLI2012 and NHANESIII consistently overestimated expiratory volumes(best fit GLI-SEA, mean [sd] z-score: FEV1 -1.29 [1.04]; FVC -1.12[1.12]). Age, height and weight were strong predictors of lung functionin our participants (P<0.001), and sex specific reference equations usingthese three variables were highly accurate in both internal validation (z-scores: FEV1 0.03 [0.99]; FVC 0.04 [0.97]; FEV1/FVC -0.03 [0.99]) andexternal validation (z-scores: FEV1 0.31 [0.99]; FVC 0.24 [0.97];FEV1/FVC 0.16 [0.91]). Further adjustment for study regions improvesthe model fit, with highest accuracy for estimation of region specific lungfunction in South Asia.Conclusion:We present improved equations for predicting lung function in SouthAsians. These offer the opportunity to enhance diagnosis andmanagement of acute and chronic lung diseases in this major globalpopulation.
Dib M-J, Ahmadi KR, Zagkos L, et al., 2022, Associations of genetically predicted vitamin B12 status across the pohenome, Nutrients, Vol: 14, ISSN: 2072-6643
Variation in vitamin B12 levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B12 status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B12 levels, serving as genetic instruments for vitamin B12 status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B12 status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B12 status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B12 status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B12 status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20–0.50) and pernicious anaemia (0.29, 0.19–0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B12 status is potentially protective of risk of vitamin B12 deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B12 status in disease diagnosis, progression and management remains to be investigated.
Eales O, Wang H, Haw D, et al., 2022, Trends in SARS-CoV-2 infection prevalence during England’s roadmap out of lockdown, January to July 2021, PLoS Computational Biology, Vol: 18, Pages: 1-16, ISSN: 1553-734X
Background:Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards.Aim:We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence.Methods:On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions.Results:Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was offset by the effects of vaccination and also affected by the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups.Conclusion:High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was effective at reducing risk of infection with school holidays/closures playing a significant part.
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