Publications
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NCD Risk Factor Collaboration NCD-RisC, Iurilli N, 2021, Heterogeneous contributions of change in population distribution of body-mass index to change in obesity and underweight, eLife, Vol: 10, ISSN: 2050-084X
From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
Riley S, Wang H, Eales O, et al., 2021, REACT-1 round 9 final report: Continued but slowing decline of prevalence of SARS-CoV-2 during national lockdown in England in February 2021
BackgroundEngland will start to exit its third national lockdown in response to the COVID-19 pandemicon 8th March 2021, with safe effective vaccines being rolled out rapidly against abackground of emerging transmissible and immunologically novel variants of SARS-CoV-2.A subsequent increase in community prevalence of infection could delay further relaxation oflockdown if vaccine uptake and efficacy are not sufficiently high to prevent increasedpressure on healthcare services.MethodsThe PCR self-swab arm of the REal-time Assessment of Community Transmission Study(REACT-1) estimates community prevalence of SARS-CoV-2 infection in England based onrandom cross-sections of the population ages five and over. Here, we present results fromthe complete round 9 of REACT-1 comprising round 9a in which swabs were collected from4th to 12th February 2021 and round 9b from 13th to 23rd February 2021. We also comparethe results of REACT-1 round 9 to round 8, in which swabs were collected mainly from 6thJanuary to 22nd January 2021.ResultsOut of 165,456 results for round 9 overall, 689 were positive. Overall weighted prevalence ofinfection in the community in England was 0.49% (0.44%, 0.55%), representing a fall of overone third from round 8. However the rate of decline of the epidemic has slowed from 15 (13,17) days, estimated for the period from the end of round 8 to the start of round 9, to 31 daysestimated using data from round 9 alone (lower confidence limit 17 days). When comparinground 9a to 9b there were apparent falls in four regions, no apparent change in one regionand apparent rises in four regions, including London where there was a suggestion ofsub-regional heterogeneity in growth and decline. Smoothed prevalence maps suggest largecontiguous areas of growth and decline that do not align with administrative regions.Prevalence fell by 50% or more across all age groups in round 9 compared to round 8, withprevalence (round 9) ranging from 0.21% in those aged 65 and over to 0
Moshe M, Daunt A, Flower B, et al., 2021, SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (REACT2): diagnostic accuracy study, BMJ: British Medical Journal, Vol: 372, Pages: 1-8, ISSN: 0959-535X
Objective: To evaluate the performance of new lateral flow immunoassays (LFIAs) suitable for use in a national COVID-19 seroprevalence programme (REACT2).Design: Laboratory sensitivity and specificity analyses were performed for seven LFIAs on a minimum of 200 sera from individuals with confirmed SARS-CoV-2 infection, and 500 pre-pandemic sera respectively. Three LFIAs were found to have a laboratory sensitivity superior to the finger-prick sensitivity of the LFIA currently used in REACT2 seroprevalence studies (84%). These LFIAs were then further evaluated through finger-prick testing on participants with confirmed previous SARS-CoV-2 infection. Two LFIAs (Surescreen, Panbio) were evaluated in clinics in June-July, 2020, and a third LFIA (AbC-19) in September, 2020. A Spike protein enzyme-linked immunoassay (S-ELISA) and hybrid double antigen binding assay (DABA) were used as laboratory reference standards.Setting: Laboratory analyses were performed at Imperial College, London and University facilities in London, UK. Research clinics for finger-prick sampling were run in two affiliated NHS trusts.Participants: Sensitivity analysis on sera were performed on 320 stored samples from previous participants in the REACT2 programme with confirmed previous SARS-CoV-2 infection. Specificity analysis was performed using 1000 pre-pandemic sera. 100 new participants with confirmed previous SARS-CoV-2 infection attended study clinics for finger-prick testing.Main outcome measures: The accuracy of LFIAs in detecting IgG antibodies to SARS-CoV-2 in comparison to two in-house ELISAs.Results: The sensitivity of seven new LFIAs using sera varied between 69% and 100% (vs S-ELISA/hybrid DABA). Specificity using sera varied between 99.6% and 100%. Sensitivity on finger-prick testing for Panbio, Surescreen and AbC-19 was 77% (CI 61.4 to 88.2), 86% (CI 72.7 to 94.8) and 69% (CI 53.8 to 81.3) respectively vs S-ELISA/hybrid DABA. Sensitivity for sera from matched clinical samples performe
Elliott J, Bodinier B, Whitaker M, et al., 2021, COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors, European Journal of Epidemiology, Vol: 36, Pages: 299-309, ISSN: 0393-2990
Background: Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank ohort, we investigate risk factors for COVID-19 mortality in comparison withnon-COVID-19mortality.MethodsWe investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N=473,550) in relation to 459 COVID-19 and 2,626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Results: Age (OR=2.76[2.18-3.49]per S.D. [8.1 years], p=2.6x10-17), male sex (OR=1.47[1.26-1.73], p=1.3x10-6) and Black versus White ethnicity (OR=1.21[1.12-1.29], p=3.0x10-7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC=0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Conclusions: Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants
Ward H, Cooke G, Whitaker M, et al., 2021, REACT-2 Round 5: increasing prevalence of SARS-CoV-2 antibodies demonstrate impact of the second wave and of vaccine roll-out in England
BackgroundEngland has experienced high rates of SARS-CoV-2 infection during the COVID-19 pandemic, affecting in particular minority ethnic groups and more deprived communities. A vaccination programme began in England in December 2020, with priority given to administering thefirst dose to the largest number of older individuals, healthcare and care home workers.MethodsA cross-sectional community survey in England undertaken between 26 January and 8 February 2021 as the fifth round of the REal-time Assessment of Community Transmission-2 (REACT-2) programme. Participants completed questionnaires, including demographic details and clinical and COVID-19 vaccination histories, and self-administered a lateral flowimmunoassay (LFIA) test to detect IgG against SARS-CoV-2 spike protein. There were sufficient numbers of participants to analyse antibody positivity after 21 days from vaccination with the PfizerBioNTech but not the AstraZeneca/Oxford vaccine which was introduced slightly later.ResultsThe survey comprised 172,099 people, with valid IgG antibody results from 155,172. The overall prevalence of antibodies (weighted to be representative of the population of England and adjusted for test sensitivity and specificity) in England was 13.9% (95% CI 13.7, 14.1) overall, 37.9% (37.2, 38.7) in vaccinated and 9.8% (9.6, 10.0) in unvaccinated people.The prevalence of antibodies (weighted) in unvaccinated people was highest in London at 16.9% (16.3, 17.5), and higher in people of Black (22.4%, 20.8, 24.1) and Asian (20.0%, 19.0, 21.0) ethnicity compared to white (8.5%, 8.3, 8.7) people. The uptake of vaccination by age was highest in those aged 80 years or older (93.5%). Vaccine confidence was high with 92.0% (91.9, 92.1) of people saying that they had accepted or intended to accept the offer.Vaccine confidence varied by age and ethnicity, with lower confidence in young people and those of Black ethnicity. Particular concerns were identified around pregnancy, fertility and alle
Riley S, Walters C, Wang H, et al., 2021, REACT-1 round 9 interim report: downward trend of SARS-CoV-2 in England in February 2021 but still at high prevalence
Background and Methods: England entered its third national lockdown of the COVID-19pandemic on 6th January 2021 with the aim of reducing the daily number of deaths andpressure on healthcare services. The real-time assessment of community transmission study(REACT-1) obtains throat and nose swabs from randomly selected people in England inorder to describe patterns of SARS-CoV-2 prevalence. Here, we report data from round 9aof REACT-1 for swabs collected between 4th and 13th February 2021.Results: Out of 85,473 tested-swabs, 378 were positive. Overall weighted prevalence ofinfection in the community in England was 0.51%, a fall of more than two thirds since our lastreport (round 8) in January 2021 when 1.57% of people tested positive. We estimate ahalving time of 14.6 days and a reproduction number R of 0.72, based on the difference inprevalence between the end of round 8 and the beginning of round 9. Although prevalencefell in all nine regions of England over the same period, there was greater uncertainty in thetrend for North West, North East, and Yorkshire and The Humber. Prevalence fellsubstantially across all age groups with highest prevalence among 18- to 24-year olds at0.89% (0.47%, 1.67%) and those aged 5 to12 years at 0.86% (0.60%, 1.24%). Largehousehold size, living in a deprived neighbourhood, and Asian ethnicity were all associatedwith increased prevalence. Healthcare and care home workers were more likely to testpositive compared to other workers.Conclusions: There is a strong decline in prevalence of SARS-CoV-2 in England among thegeneral population five to six weeks into lockdown, but prevalence remains high: at levelssimilar to those observed in late September 2020. Also, the number of COVID-19 cases inhospitals is higher than at the peak of the first wave in April 2020. The effects of easing ofsocial distancing when we transition out of lockdown need to be closely monitored to avoid aresurgence in infections and renewed pressure on health services.
Ward H, Atchison C, Whitaker M, et al., 2021, SARS-CoV-2 antibody prevalence in England following the first peak of the pandemic., Nature Communications, Vol: 12, Pages: 1-8, ISSN: 2041-1723
England has experienced a large outbreak of SARS-CoV-2, disproportionately affecting people from disadvantaged and ethnic minority communities. It is unclear how much of this excess is due to differences in exposure associated with structural inequalities. Here we report from the REal-time Assessment of Community Transmission-2 (REACT-2) national study of over 100,000 people. After adjusting for test characteristics and re-weighting to the population, overall antibody prevalence is 6.0% (95% CI: 5.8-6.1). An estimated 3.4 million people had developed antibodies to SARS-CoV-2 by mid-July 2020. Prevalence is two- to three-fold higher among health and care workers compared with non-essential workers, and in people of Black or South Asian than white ethnicity, while age- and sex-specific infection fatality ratios are similar across ethnicities. Our results indicate that higher hospitalisation and mortality from COVID-19 in minority ethnic groups may reflect higher rates of infection rather than differential experience of disease or care.
Elliott J, Whitaker M, Bodinier B, et al., 2021, Symptom reporting in over 1 million people: community detection of COVID-19
Control of the SARS-CoV-2 epidemic requires rapid identification and isolation of infectedindividuals and their contacts. Community testing in England (Pillar 2) by polymerase chainreaction (PCR) is reserved for those reporting at least one of four ‘classic’ COVID-19 symptoms(loss or change of sense of smell, loss or change of sense of taste, fever, new continuous cough). 1Detection of positive cases in the community might be improved by including additionalsymptoms and their combinations. We used data from the REal-time Assessment of CommunityTransmission-1 (REACT-1) study to investigate symptom profiles for PCR positivity at differentages. Among rounds 2–7 (June to December 2020), an age-stratified, variable selection approachstably selected chills (all ages), headache (5–17 years), appetite loss (18–54 and 55+ years) andmuscle aches (18–54 years) as jointly and positively predictive of PCR positivity together withthe classic four symptoms. Between round 7 (November to December 2020) and round 8(January 2021) when new variant B.1.1.7 predominated, only loss or change of sense of smell(more predictive in round 7) and (borderline) new persistent cough (more predictive in round 8)differed between cases. At any level of PCR testing, triage based on the symptoms identifiedhere would result in more cases detected than the current approach .
Gill D, Cameron AC, Burgess S, et al., 2021, Urate, blood pressure and cardiovascular disease: evidence from Mendelian randomization and meta-analysis of clinical trials, Hypertension, Vol: 77, Pages: 383-392, ISSN: 0194-911X
Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10–1.30]; P=4×10−5), peripheral artery disease (1.12 [95% CI, 1.03–1.21]; P=9×10−3), and stroke (1.11 [95% CI, 1.05–1.18]; P=2×10−4). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, −2.55 mm Hg [95% CI, −4.06 to −1.05]; P=1×10−3) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22–0.73]; P=3×10−3) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44–1.03]; P=0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.
Riley S, Eales O, Walters C, et al., 2021, REACT-1 round 8 final report: high average prevalence with regional heterogeneity of trends in SARS-CoV-2 infection in the community in England during January 2021
In early January 2021, England entered its third national lockdown of the COVID-19 pandemic to reduce numbers of deaths and pressure on healthcare services, while rapidly rolling out vaccination to healthcare workers and those most at risk of severe disease and death. REACT-1 is a survey of SARS-CoV-2 prevalence in the community in England, based on repeated cross-sectional samples of the population. Between 6th and 22nd January 2021, out of 167,642 results, 2,282 were positive giving a weighted national prevalence of infection of 1.57% (95% CI, 1.49%, 1.66%). The R number nationally over this period was estimated at 0.98 (0.92, 1.04). Prevalence remained high throughout, but with suggestion of a decline at the end of the study period. The average national trend masked regional heterogeneity, with robustly decreasing prevalence in one region (South West) and increasing prevalence in another (East Midlands). Overall prevalence at regional level was highest in London at 2.83% (2.53%, 3.16%). Although prevalence nationally was highest in the low-risk 18 to 24 year old group at 2.44% (1.96%, 3.03%), it was also high in those over 65 years who are most at risk, at 0.93% (0.82%, 1.05%). Large household size, living in a deprived neighbourhood, and Black and Asian ethnicity were all associated with higher levels of infections compared to smaller households, less deprived neighbourhoods and other ethnicities. Healthcare and care home workers, and other key workers, were more likely to test positive compared to other workers. If sustained lower prevalence is not achieved rapidly in England, pressure on healthcare services and numbers of COVID-19 deaths will remain unacceptably high.
Ware J, Tadros R, Francis C, et al., 2021, Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect, Nature Genetics, Vol: 53, Pages: 128-134, ISSN: 1061-4036
The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young otherwise healthy individuals. We conducted genome-wide association studies (GWAS) and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases), and nine left ventricular (LV) traits in 19,260 UK Biobank participants with structurally-normal hearts. We identified 16 loci associated with HCM, 13 with DCM, and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased contractility with HCM risk. A polygenic risk score (PRS) explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that PRS may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.
Riley S, Wang H, Eales O, et al., 2021, REACT-1 round 8 interim report: SARS-CoV-2 prevalence during the initial stages of the third national lockdown in England, Publisher: Imperial College London
BackgroundHigh prevalence of SARS-CoV-2 virus in many northern hemisphere populations is causingextreme pressure on healthcare services and leading to high numbers of fatalities. Eventhough safe and effective vaccines are being deployed in many populations, the majority ofthose most at-risk of severe COVID-19 will not be protected until late spring, even incountries already at a more advanced stage of vaccine deployment.MethodsThe REal-time Assessment of Community Transmission study-1 (REACT-1) obtains throatand nose swabs from between 120,000 and 180,000 people in the community in England atapproximately monthly intervals. Round 8a of REACT-1 mainly covers a period from 6thJanuary 2021 to 15th January 2021. Swabs are tested for SARS-CoV-2 virus and patterns ofswab-positivity are described over time, space and with respect to individual characteristics.We compare swab-positivity prevalence from REACT-1 with mobility data based on the GPSlocations of individuals using the Facebook mobile phone app. We also compare resultsfrom round 8a with those from round 7 in which swabs were collected from 13th Novemberto 24th November (round 7a) and 25th November to 3rd December 2020 (round 7b).ResultsIn round 8a, we found 1,962 positives from 142,909 swabs giving a weighted prevalence of1.58% (95% CI, 1.49%, 1.68%). Using a constant growth model, we found no strongevidence for either growth or decay averaged across the period; rather, based on data froma limited number of days, prevalence may have started to rise at the end of round 8a.Facebook mobility data showed a marked decrease in activity at the end of December 2020,followed by a rise at the start of the working year in January 2021. Between round 7b andround 8a, prevalence increased in all adult age groups, more than doubling to 0.94%(0.83%, 1.07%) in those aged 65 and over. Large household size, living in a deprivedneighbourhood, and Black and Asian ethnicity were all associated with increasedprevalence. Both healthcare
Evangelou E, Suzuki H, Bai W, et al., 2021, Alcohol consumption is associated with structural changes in various organ systems: A population-based study in UK Biobank
<jats:title>Abstract</jats:title><jats:p>Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample. We assessed global effects of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta and liver of UK-Biobank participants who reported drinking alcohol. We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (–1.7×10<jats:sup>−3</jats:sup>±0.76×10<jats:sup>−3</jats:sup> per doubling of alcohol consumption, <jats:italic>P</jats:italic>=3.0×10<jats:sup>−14</jats:sup>). Alcohol consumption also was associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption. Our results imply that there is not a “safe threshold” below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.</jats:p>
Aljuraiban G, Chan Q, Gibson R, et al., 2021, Association between plant-based diets and blood pressure in the INTERMAP study, BMJ Nutrition, Prevention & Health, Vol: 3, Pages: 133-142, ISSN: 2516-5542
Background Plant-based diets are associated with a lower risk of cardiovascular diseases; however, little is known how the healthiness of the diet may be associated with blood pressure (BP). We aimed to modify three plant -based diet indices: overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI) according to country-specific dietary guidelines to enable use across populations with diverse dietary patterns – and assessed their associations with BP.Design We used cross-sectional data including 4,680 men and women ages 40–59y in Japan, China, the United Kingdom, and the United States from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP). During four visits, eight BP measurements, and four 24-h dietary recalls were collected. Multivariable regression coefficients were estimated, pooled, weighted, and adjusted extensively for lifestyle/dietary confounders.Results Modified PDI was not associated with BP. Consumption of hPDI higher by 1SD was inversely associated with systolic (-0.82 mm Hg;95% CI:-1.32,-0.49) and diastolic BP (-0.49 mm Hg; 95% CI:-0.91, -0.28). In contrast, consumption of an uPDI was directly associated with systolic (0.77 mm Hg;95% CI:0.30,1.20). Significant associations between hPDI with BP were attenuated with separate adjustment for vegetables and whole grains; associations between uPDI and BP were attenuated after adjustment for refined grains, sugar-sweetened beverages, and meat.Conclusion An hPDI is associated with lower BP while a uPDI is adversely related to BP. Plant-based diets rich in vegetables and whole grains and limited in refined grains, sugar-sweetened beverages, and total meat may contribute to these associations. In addition to current guidelines, the nutritional quality of consumed plant foods is as important as limiting animal-based components.
Allen NE, Arnold M, Parish S, et al., 2021, Approaches to minimising the epidemiological impact of sources of systematic and random variation that may affect biochemistry assay data in UK Biobank, Wellcome Open Research, Vol: 5, Pages: 222-222
<ns3:p><ns3:bold>Background</ns3:bold>: UK Biobank is a large prospective study that recruited 500,000 participants aged 40 to 69 years, between 2006-2010.The study has collected (and continues to collect) extensive phenotypic and genomic data about its participants. In order to enhance further the value of the UK Biobank resource, a wide range of biochemistry markers were measured in all participants with an available biological sample. Here, we describe the approaches UK Biobank has taken to minimise error related to sample collection, processing, retrieval and assay measurement.</ns3:p><ns3:p> <ns3:bold>Methods</ns3:bold>: During routine quality control checks, the laboratory team observed that some assay results were lower than expected for samples acquired during certain time periods. Analyses were undertaken to identify and correct for the unexpected dilution identified during sample processing, and for expected error caused by laboratory drift of assay results.</ns3:p><ns3:p> <ns3:bold>Results</ns3:bold>: The vast majority (92%) of biochemistry serum assay results were assessed to be not materially affected by dilution, with an estimated difference in concentration of less than 1% (i.e. either lower or higher) than that expected if the sample were unaffected; 8.3% were estimated to be diluted by up to 10%; very few samples appeared to be diluted more than this. Biomarkers measured in urine (creatinine, microalbumin, sodium, potassium) and red blood cells (HbA1c) were not affected. In order to correct for laboratory variation over the assay period, all assay results were adjusted for date of assay, with the exception of those that had a high biological coefficient of variation or evident seasonal variability: vitamin D, lipoprotein (a), gamma glutamyltransferase, C-reactive protein and rheumatoid factor.</ns3:p><ns3:p> <ns3:bold>Conclusions</ns3:bold>: Rigorous approaches
Matsumoto-Yamauchi H, Kondo K, Miura K, et al., 2021, Relationships of alcohol consumption with coronary risk factors and macro- and micro-nutrient intake in Japanese people: The INTERLIPID study, Journal of Nutritional Science and Vitaminology, Vol: 67, Pages: 28-38, ISSN: 0287-3516
Several studies have reported a J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk. However, the mechanisms of this relationship remain unclear. This study aimed to evaluate the relationships of alcohol consumption with established CHD risk factors and with macro-/micro-nutrient intake among Japanese people. Participants were 1,090 Japanese men and women aged 40–59 y enrolled in the INTERLIPID study, excluding former drinkers. Based on two 7-d alcohol records, participants were classified as non-drinkers (0 g/wk), light-drinkers (<100 g/wk), moderate-drinkers (100–299 g/wk), or heavy-drinkers (≥300 g/wk). Detailed macro-/micro-nutrient intake was evaluated using four in-depth 24-h dietary recalls and adjusted for total energy intake excluding alcohol. We analyzed the associations of CHD risk factors and nutrient intake with alcohol consumption. Serum high-density lipoprotein cholesterol and blood pressure were higher and low-density lipoprotein cholesterol was lower among those with higher alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smokers, number of cigarettes smoked, and prevalence of hypertension; these risk factors were lowest among light-drinkers. Carbohydrate and total fiber intakes were lower and protein and dietary cholesterol intakes were higher among those with higher alcohol consumption. These associations were similar for men and women. Alcohol consumption was related to nutrient intake as well as established CHD risk factors. Non-drinkers were higher on some CHD risk factors than were light-drinkers. These findings may influence the J-shaped relationship between alcohol consumption and CHD risk.
Lagou V, Jiang L, Ulrich A, et al., 2021, Random glucose GWAS in 493,036 individuals provides insights into diabetes pathophysiology, complications and treatment stratification, medRxiv
Homeostatic control of blood glucose requires different physiological responses in the fasting and post-prandial states. We reasoned that glucose measurements under non-standardised conditions (random glucose; RG) may capture diverse glucoregulatory processes more effectively than previous genome-wide association studies (GWAS) of fasting glycaemia or after standardised glucose loads. Through GWAS meta-analysis of RG in 493,036 individuals without diabetes of diverse ethnicities we identified 128 associated loci represented by 162 distinct signals, including 14 with sex-dimorphic effects, 9 discovered through trans-ethnic analysis, and 70 novel signals for glycaemic traits. Novel RG loci were particularly enriched in expression in the ileum and colon, indicating a prominent role for the gastrointestinal tract in the control of blood glucose. Functional studies and molecular dynamics simulations of coding variants of GLP1R, a well-established type 2 diabetes treatment target, provided a genetic framework for optimal selection of GLP-1R agonist therapy. We also provided new evidence from Mendelian randomisation that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Thus, our approach based on RG GWAS provided wide-ranging insights into the biology of glucose regulation, diabetes complications and the potential for treatment stratification.Competing Interest StatementAlejandra Tomas has received grant funding from Sun Pharmaceuticals. Ivan R Corrêa, Jr is an employee of New England Biolabs, Inc., a manufacturer and vendor of reagents for life science research. Mark J Caulfield is Chief Scientist for Genomics England, a UK Government company. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Mark McCarthy has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo No
Zhou B, Carrillo-Larco RM, Danaei G, et al., 2021, Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants, The Lancet, Vol: 398, Pages: 957-980, ISSN: 0140-6736
Shen C, Dumontheil I, Thomas M, et al., 2020, Digital Technology Use and BMI: Evidence From a Cross-sectional Analysis of an Adolescent Cohort Study (Preprint)
<sec> <title>BACKGROUND</title> <p>The use of digital technology such as mobile phones is ubiquitous in adolescents. However, excessive use may have adverse health effects, possibly partially mediated by disruptions to sleep.</p> </sec> <sec> <title>OBJECTIVE</title> <p>This study aims to assess the social predictors of digital technology use and their cross-sectional association with BMI z scores and being overweight in a large sample of adolescents.</p> </sec> <sec> <title>METHODS</title> <p>We used baseline data from a subset of a large adolescent cohort from 39 schools across Greater London who participated in the Study of Cognition, Adolescents and Mobile Phones (n=1473). Digital technology use included phone calls, internet use on mobile phones, and video gaming on any device. Multilevel regression was used to assess the associations between digital technology use and age-specific and sex-specific BMI z scores and being overweight (including obesity). Measurements were derived from height and weight, obtained by the Tanita BC-418 Body Composition Analyzer. We examined whether these associations were mediated by insufficient sleep.</p> </sec> <sec> <title>RESULTS</title> <p>Generally, participants with lower socioeconomic status reported more use of digital technology. Controlling for socioeconomic status, internet use on mobile phones for more than 3 hours per day was associated with higher BMI z scores (adjusted β=.30, 95% CI 0.11-0.48) and greater odds of being overweight (adjusted odds ratio 1.60, 95% CI 1.09-2.34), compar
Riley S, Walters C, Wang H, et al., 2020, REACT-1 round 7 updated report: regional heterogeneity in changes in prevalence of SARS-CoV-2 infection during the second national COVID-19 lockdown in England, REACT-1 round 7 updated report: regional heterogeneity in changes in prevalence of SARS-CoV-2 infection during the second national COVID-19 lockdown in England, London, Publisher: Imperial College London
BackgroundEngland exited a four-week second national lockdown on 2nd December 2020 initiated in response to the COVID-19 pandemic. Prior results showed that prevalence dropped during the first half of lockdown, with greater reductions in higher-prevalence northern regions.MethodsREACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England, designed to monitor the spread of the epidemic and thus increase situational awareness. Round 7 of REACT-1 commenced swab-collection on 13th November 2020. A prior interim report included data from 13th to 24th November 2020 for 105,122 participants. Here, we report data for the entire round with swab results obtained up to 3rd December 2020.ResultsBetween 13th November and 3rd December (round 7) there were 1,299 positive swabs out of 168,181 giving a weighted prevalence of 0.94% (95% CI 0.87%, 1.01%) or 94 per 10,000 people infected in the community in England. This compares with a prevalence of 1.30% (1.21%, 1.39%) from 16th October to 2nd November 2020 (round 6), a decline of 28%. Prevalence during the latter half of round 7 was 0.91% (95% CI, 0.81%, 1.03%) compared with 0.96% (0.87%, 1.05%) in the first half. The national R number in round 7 was estimated at 0.96 (0.88, 1.03) with a decline in prevalence observed during the first half of this period no longer apparent during the second half at the end of lockdown. During round 7 there was a marked fall in prevalence in West Midlands, a levelling off in some regions and a rise in London. R numbers at regional level ranged from 0.60 (0.41, 0.80) in West Midlands up to 1.27 (1.04, 1.54) in London, where prevalence was highest in the east and south-east of the city. Nationally, between 13th November and 3rd December, the highest prevalence was in school-aged children especially at ages 13-17 years at 2.04% (1.69%, 2.46%), or approximately 1 in 50.ConclusionBetween the previous round and round 7 (during lockdown), there was a fall in prevalence of SARS-C
Lee M, Carter E, Yan L, et al., 2020, Determinants of personal exposure to PM2.5 and black carbon in Chinese adults: a 1 repeated-measures study in villages using solid fuel energy, Environment International, Vol: 146, ISSN: 0160-4120
Exposure to air pollution is a leading health risk factor. The variance components and contributions of indoor versus outdoor source determinants of personal exposure to air pollution are poorly understood, especially in settings of household solid fuel use. We conducted a panel study with up to 4 days of repeated measures of integrated gravimetric personal exposure to PM2.5 and black carbon in 787 men and women (ages 40-79) living in peri-urban villages in northern (Beijing and Shanxi) and southern (Guangxi) China. We simultaneously measured outdoor PM2.5 and collected questionnaire data on sociodemographic characteristics and indoor pollution sources including tobacco smoking and solid fuel stove use. We obtained over 2000 days of personal exposure monitoring which showed higher exposures in the heating season (geometric mean (GM): 108 versus 65 μg/m3 in the non-heating season for PM2.5) and among northern participants (GM: 90 versus 59 μg/m3 in southern China in the non-heating season for PM2.5). We used mixed-effects models to estimate within- and between-participant variance components and to assess the determinants of exposures. Within-participant variance in exposure dominated the total variability (68-95%). Outdoor PM2.5 was the dominant variable for explaining within-participant variance in exposure to PM2.5 (16%). Household fuel use (PM2.5: 8%; black carbon: 10%) and smoking status (PM2.5: 27%; black carbon: 5%) explained the most between-participant variance. Indoor sources (solid fuel stoves, tobacco smoking) were associated with 13-30% higher exposures to air pollution and each 10 μg/m3 increase in outdoor PM2.5 was associated with 6-8% higher exposure. Our findings indicate that repeated measurements of daily exposure are likely needed to capture longer-term exposures in settings of household solid fuel use, even within a single season, and that reducing air pollution from both outdoor and indoor sources is likely needed to achieve measurable
Riley S, Eales O, Walters C, et al., 2020, REACT-1 round 7 interim report: fall in prevalence of swab-positivity in England during national lockdown, Publisher: Cold Spring Harbor Laboratory
Background The second wave of the 2020 COVID-19 pandemic in England has been characterized by high growth and prevalence in the North with lower prevalence in the South. High prevalence was first observed at younger adult ages before spreading out to school-aged children and older adults. Local tiered interventions were in place up to 5th November 2020 at which time a second national lockdown was implemented.Methods REACT-1 is a repeated cross-sectional survey of SARS-CoV-2 swab-positivity in random samples of the population of England. The current period of data collection (round 7) commenced on 13th November 2020 and we report interim results here for swabs collected up to and including 24th November 2020. Because there were two distinct periods of growth during the previous round 6, here we compare results from round 7 (mainly) with the second half of round 6, which obtained swabs between 26th October and 2nd November 2020. We report prevalence both unweighted and reweighted to be representative of the population of England. We describe trends in unweighted prevalence with daily growth rates, doubling times, reproduction numbers (R) and splines. We estimated odds ratios for swab-positivity using mutually-adjusted multivariable logistic regression models.Results We found 821 positives from 105,123 swabs giving an unweighted prevalence of 0.78% (95% CI, 0.73%, 0.84%) and a weighted prevalence of 0.96% (0.87%, 1.05%). The weighted prevalence estimate was ∼30% lower than that of 1.32% (1.20%, 1.45%) obtained in the second half of round 6. This decrease corresponds to a halving time of 37 (30, 47) days and an R number of 0.88 (0.86, 0.91). Using only data from the most recent period, we estimate an R number of 0.71 (0.54, 0.90). A spline fit to prevalence showed a rise shortly after the previous period of data collection followed by a fall coinciding with the start of lockdown. The national trends were driven mainly by reductions in higher-prevalence northern regi
Chadeau M, Bodinier B, Vermeulen R, et al., 2020, Education, biological ageing, all-cause and cause-specific mortality and morbidity: UK Biobank Cohort Study, EClinicalMedicine, Vol: 29-30, ISSN: 2589-5370
BackgroundSocioeconomic position as measured by education may be embodied and affect the functioning of key physiological systems. Links between social disadvantage, its biological imprint, and cause-specific mortality and morbidity have not been investigated in large populations, and yet may point towards areas for public health interventions beyond targeting individual behaviours.MethodsUsing data from 366,748 UK Biobank participants with 13 biomarker measurements, we calculated a Biological Health Score (BHS, ranging from 0 to 1) capturing the level of functioning of five physiological systems. Associations between BHS and incidence of cardiovascular disease (CVD) and cancer, and mortality from all, CVD, cancer, and external causes were examined. We explored the role of education in these associations. Mendelian randomisation using genetic evidence was used to triangulate these findings.FindingsAn increase in BHS of 0.1 was associated with all-cause (HR = 1.14 [1.12–1.16] and 1.09 [1.07–1.12] in men and women respectively), cancer (HR = 1.11 [1.09–1.14] and 1.07 [1.04–1.10]) and CVD (HR = 1.25 [1.20–1.31] and 1.21 [1.11–1.31]) mortality, CVD incidence (HR = 1.15 [1.13–1.16] and 1.17 [1.15–1.19]). These associations survived adjustment for education, lifestyle-behaviours, body mass index (BMI), co-morbidities and medical treatments. Mendelian randomisation further supported the link between the BHS and CVD incidence (HR = 1.31 [1.21–1.42]). The BHS contributed to CVD incidence prediction (age-adjusted C-statistic = 0.58), other than through education and health behaviours.InterpretationThe BHS captures features of the embodiment of education, health behaviours, and more proximal unknown factors which all complementarily contribute to all-cause, cancer and CVD morbidity and premature death.
Mustafa R, Mens M, Pinto R, et al., 2020, Identifying metabolomic fingerprints of microRNAs in cardiovascular disorders, Publisher: SPRINGERNATURE, Pages: 277-277, ISSN: 1018-4813
Surendran P, Gao H, Zhang W, et al., 2020, Discovery of rare variants associated with blood pressure regulation trhough meta-analaysis of 1.3 million individuals, Nature Genetics, Vol: 52, Pages: 1314-1332, ISSN: 1061-4036
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency, MAF > 0.05). In a meta-analysis of up to >1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (MAF≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated SNVs within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (e.g.GATA5, PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
Cabrera CP, Pazoki R, Giri A, et al., 2020, Multi-trait genome-wide association analysis of blood pressure identifies 45 additional loci, Publisher: SPRINGERNATURE, Pages: 105-105, ISSN: 1018-4813
Kolbeinsson A, Filippi S, Panagakis I, et al., 2020, Accelerated MRI-predicted brain ageing and its associations with cardiometabolic and brain disorders, Scientific Reports, Vol: 10, ISSN: 2045-2322
Brain structure in later life reflects both influences of intrinsic aging and those of lifestyle, environment and disease. We developed a deep neural network model trained on brain MRI scans of healthy people to predict “healthy” brain age. Brain regions most informative for the prediction included the cerebellum, hippocampus, amygdala and insular cortex. We then applied this model to data from an independent group of people not stratified for health. A phenome-wide association analysis of over 1,410 traits in the UK Biobank with differences between the predicted and chronological ages for the second group identified significant associations with over 40 traits including diseases (e.g., type I and type II diabetes), disease risk factors (e.g., increased diastolic blood pressure and body mass index), and poorer cognitive function. These observations highlight relationships between brain and systemic health and have implications for understanding contributions of the latter to late life dementia risk.
Stevelink SAM, Opie E, Pernet D, et al., 2020, Probable PTSD, depression and anxiety in 40,299 UK police officers and staff: Prevalence, risk factors and associations with blood pressure, PLoS One, Vol: 15, ISSN: 1932-6203
INTRODUCTION: Police employees undertake challenging duties which may adversely impact their health. This study explored the prevalence of and risk factors for probable mental disorders amongst a representative sample of UK police employees. The association between mental illness and alterations in blood pressure was also explored. METHODS: Data were used from the Airwave Health Monitoring Study which was established to monitor the possible physical health impacts of a new communication system on police employees. Data included sociodemographic characteristics, lifestyle habits, depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms and blood pressure. Descriptive statistics were used to explore the prevalence of probable mental disorders and associated factors. Stepwise linear regression was conducted, controlling for confounding variables, to examine associations between mental disorders and blood pressure. RESULTS: The sample included 40,299 police staff, police constable/sergeants and inspectors or above. Probable depression was most frequently reported (9.8%), followed by anxiety (8.5%) and PTSD (3.9%). Groups at risk for probable mental disorders included police staff, and police employees who reported drinking heavily. Police employees exposed to traumatic incidents in the past six months had a doubling in rates of anxiety or depression and a six-fold increase in PTSD compared to those with no recent trauma exposure. Adjusted logistic regression models did not reveal any significant association between probable mental disorders and systolic blood pressure but significantly elevated diastolic blood pressure (≈1mmHg) was found across mental disorders. CONCLUSIONS: These results show lower rates of probable mental disorders, especially PTSD, than reported in other studies focusing on police employees. Although mental ill health was associated with increased diastolic blood pressure, this was unlikely to be clinically significant. These fin
Riley S, Ainslie K, Eales O, et al., 2020, REACT-1 round 6 updated report: high prevalence of SARS-CoV-2 swab positivity with reduced rate of growth in England at the start of November 2020
BackgroundEngland is now in the midst of its second wave of the COVID-19 pandemic. Multiple regions of the country are at high infection prevalence and all areas experienced rapid recent growth of the epidemic during October 2020.MethodsREACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England designed to monitor the spread of the epidemic and thus increase situational awareness. Round 6 of REACT-1 commenced swab-collection on 16th October. A prior interim report included data from 16th to 25th October for 85,971 participants. Here, we report data for the entire round on 160,175 participants with swab results obtained up to 2nd November 2020.ResultsOverall weighted prevalence of infection in the community in England was 1.3% or 130 people per 10,000 infected, up from 60 people per 10,000 in the round 5 report (18th September to 5th October 2020), doubling every 24 days on average since the prior round. The corresponding R number was estimated to be 1.2. Prevalence of infection was highest in North West (2.4%, up from 1.2% ), followed by Yorkshire and The Humber (2.3% up from 0.84%), West Midlands (1.6% up from 0.60%), North East (1.5% up from 1.1%), East Midlands (1.3% up from 0.56%), London (0.97%, up from 0.54%), South West (0.80% up from 0.33%), South East (0.69% up from 0.29%), and East of England (0.69% up from 0.30%). Rapid growth in the South observed in the first half of round 6 was no longer apparent in the second half of round 6. We also observed a decline in prevalence in Yorkshire and The Humber during this period. Comparing the first and second halves of round 6, there was a suggestion of decline in weighted prevalence in participants aged 5 to 12 years and in those aged 25 to 44 years. While prevalence remained high, in the second half of round 6 there was suggestion of a slight fall then rise that was seen nationally and also separately in both the North and the South.ConclusionThe impact of the second national lockdown
Rodriguez-Martinez A, Zhou B, Sophiea MK, et al., 2020, Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants, The Lancet, Vol: 396, Pages: 1511-1524, ISSN: 0140-6736
SummaryBackgroundComparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents.MethodsFor this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence.FindingsWe pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became
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