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1. Identifying barriers and facilitators to increase fibre intakes in UK primary school children and exploring the acceptability of intervention components: a UK qualitative study

Author

Angela S Donin, Lucy P Goldsmith, Clare Sharp, Charlotte Wahlich, Peter H Whincup, and Michael H Ussher

Subjects
School-based interventions, Dietary fibre, Children, Obesity, Healthy diet, Public aspects of medicine, RA1-1270, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Objective: Within the UK, dietary fibre intakes are well below recommended intakes and associated with increased risk of obesity. This study aimed to explore the views of parents and children on barriers and facilitators to increasing fibre intakes and improving diets, alongside investigating the appropriateness of intervention components to overcome modifiable barriers. Design: Qualitative study including semi-structured interviews and focus groups informed by the Theoretical Domains Framework (TDF) and the Capability-Opportunity-Motivation-Behaviour (COM-B) model. Participants: Year 5 children (aged 9–10-years) and parents, recruited through London primary schools Results: A total of twenty-four participants (eleven parents and thirteen children) took part. Five key themes were identified as barriers and facilitators, namely lack of (and improving) knowledge, social factors (including parent–child conflicts, limited time for food preparation, influence of peer and family members), current eating habits, influence of the school, community and home environment in shaping eating behaviours, and the importance of choice and variety in finding foods that are healthy and tasty. Parents strongly supported school-based dietary interventions to enable consistent messaging at home and school and help support dietary behaviour change. Practical sessions (such as workshops to strengthen knowledge, taste tests and food swap ideas) were supported by parents and children. Conclusions: By using a theory-driven approach to explore the barriers and facilitators to increasing fibre intake, this research identified important themes and modifiable barriers to behaviour change and identifies acceptable intervention components to overcome barriers and bring about sustained dietary behaviour change in primary school children.

Published
2024
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2. Influence of neighborhood-level socioeconomic deprivation and individual socioeconomic position on risk of developing type 2 diabetes in older men: a longitudinal analysis in the British Regional Heart Study cohort

Author

Sheena E Ramsay, Lucy T Lennon, S Goya Wannamethee, Judith Rankin, Peter H Whincup, A Olia Papacosta, and Kathryn J Bush

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction Evidence from longitudinal studies on the influence of neighborhood socioeconomic deprivation in older age on the development of type 2 diabetes mellitus (T2DM) is limited. This study investigates the prospective associations of neighborhood-level deprivation and individual socioeconomic position (SEP) with T2DM incidence in older age.Research design and methods The British Regional Heart Study studied 4252 men aged 60–79 years in 1998–2000. Neighborhood-level deprivation was based on the Index of Multiple Deprivation quintiles for participants’ 1998–2000 residential postcode. Individual SEP was defined as social class based on longest-held occupation. A cumulative score of individual socioeconomic factors was derived. Incident T2DM cases were ascertained from primary care records; prevalent cases were excluded. Cox proportional hazard models were used to examine the associations.Results Among 3706 men, 368 incident cases of T2DM were observed over 18 years. The age-adjusted T2DM risk increased from the least deprived quintile to the most deprived: HR per quintile increase 1.14 (95% CI 1.06 to 1.23) (p=0.0005). The age-adjusted T2DM HR in social class V (lowest) versus social class I (highest) was 2.45 (95% CI 1.36 to 4.42) (p=0.001). Both associations attenuated but remained significant on adjustment for other deprivation measures, becoming non-significant on adjustment for body mass index and T2DM family history. T2DM risk increased with cumulative individual adverse socioeconomic factors: HR per point increase 1.14 (95% CI 1.05 to 1.24).Conclusions Inequalities in T2DM risk persist in later life, both in relation to neighborhood-level and individual-level socioeconomic factors. Underlying modifiable risk factors continue to need to be addressed in deprived older age populations to reduce disease burden.

Published
2023
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3. GWAS on retinal vasculometry phenotypes.

Author

Xiaofan Jiang, Pirro G Hysi, Anthony P Khawaja, Omar A Mahroo, Zihe Xu, Christopher J Hammond, Paul J Foster, Roshan A Welikala, Sarah A Barman, Peter H Whincup, Alicja R Rudnicka, Christopher G Owen, David P Strachan, and UK Biobank Eye and Vision Consortium

Subjects
Genetics, QH426-470
Abstract

The eye is the window through which light is transmitted and visual sensory signalling originates. It is also a window through which elements of the cardiovascular and nervous systems can be directly inspected, using ophthalmoscopy or retinal imaging. Measurements of ocular parameters may therefore offer important information on the physiology and homeostasis of these two important systems. Here we report the results of a genetic characterisation of retinal vasculature. Four genome-wide association studies performed on different aspects of retinal vasculometry phenotypes, such as arteriolar and venular tortuosity and width, found significant similarities between retinal vascular characteristics and cardiometabolic health. Our analyses identified 119 different regions of association with traits of retinal vasculature, including 89 loci associated arteriolar tortuosity, the strongest of which was rs35131825 (p = 2.00×10-108), 2 loci with arteriolar width (rs12969347, p = 3.30×10-09 and rs5442, p = 1.9E-15), 17 other loci associated with venular tortuosity and 11 novel associations with venular width. Our causal inference analyses also found that factors linked to arteriolar tortuosity cause elevated diastolic blood pressure and not vice versa.

Published
2023
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4. Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts

Author

Amanda E Paluch, PhD, Shivangi Bajpai, MS, David R Bassett, ProfPhD, Mercedes R Carnethon, ProfPhD, Ulf Ekelund, ProfPhD, Kelly R Evenson, ProfPhD, Deborah A Galuska, PhD, Barbara J Jefferis, PhD, William E Kraus, ProfMD, I-Min Lee, ProfScD, Charles E Matthews, PhD, John D Omura, MD, Alpa V Patel, PhD, Carl F Pieper, DrPH, Erika Rees-Punia, PhD, Dhayana Dallmeier, PhD, Jochen Klenk, ProfPhD, Peter H Whincup, ProfPhD, Erin E Dooley, PhD, Kelley Pettee Gabriel, ProfPhD, Priya Palta, PhD, Lisa A Pompeii, ProfPhD, Ariel Chernofsky, MS, Martin G Larson, PhD, Ramachandran S Vasan, ProfMD, Nicole Spartano, PhD, Marcel Ballin, MSc, Peter Nordström, ProfPhD, Anna Nordström, PhD, Sigmund A Anderssen, ProfPhD, Bjørge H Hansen, ProfPhD, Jennifer A Cochrane, BA, Terence Dwyer, ProfMD, Jing Wang, PhD, Luigi Ferrucci, PhD, Fangyu Liu, MHS, Jennifer Schrack, PhD, Jacek Urbanek, PhD, Pedro F Saint-Maurice, PhD, Naofumi Yamamoto, PhD, Yutaka Yoshitake, PhD, Robert L Newton, Jr, PhD, Shengping Yang, PhD, Eric J Shiroma, ScD, and Janet E Fulton, PhD

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. Methods: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose–response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. Findings: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3–9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51–0·71) for quartile 2, 0·55 (0·49–0·62) for quartile 3, and 0·47 (0·39–0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000–8000 steps per day and among adults younger than 60 years until 8000–10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56–0·83]) and a peak of 60 min (0·67 [0·50–0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96–1·32]) and 100 steps per min or faster (0·86 [0·58–1·28]). Interpretation: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. Funding: US Centers for Disease Control and Prevention.

Published
2022
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5. Frailty and incident heart failure in older men: the British Regional Heart Study

Author

Sheena E Ramsay, Lucy T Lennon, S Goya Wannamethee, Peter H Whincup, Douglas GJ McKechnie, and A Olia Papacosta

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective Frailty and heart failure (HF) are cross-sectionally associated. Published longitudinal data are very limited. We sought to investigate associations between frailty and incident HF.Methods Prospective study of 1722 men, examined at age 72–91 years. Scores based on the Fried phenotype, Gill index and a novel frailty score, based on the Health Ageing and Body Composition Battery, incorporating slow walking speed, low chair-stand time and subjective difficulty with balance, were calculated. Associations between these scores and incident HF were analysed with Cox proportional hazard modelling.Results 1445 men with frailty data and without prevalent HF were included. 99 developed HF (mean follow-up 6.1 years). Men scoring 3/3 on our novel frailty score had elevated risk of incident HF (HR 2.77, 95% CI 1.25 to 6.15), which persisted after adjustment for established risk factors and interleukin-6 (HR 3.14, 95% CI 1.35 to 7.31). This risk remained increased, although attenuated, after excluding HF events within 2 years of baseline (HR 2.05, 95% CI 0.61 to 6.92). The frailty phenotype showed a non-significant association with HF (age-adjusted HR 1.92, 95% CI 0.99 to 3.73), which was further attenuated after adjustment for prevalent coronary heart disease and Body mass index (HR 1.60, 95% CI 0.81 to 3.15). Gill-type scores were weakly associated with HF risk after these adjustments (HR 1.31, 95% CI 0.47 to 3.70).Conclusion In these older men, the combination of slow walk speed, low sit-stand time and balance problems were associated with high risk of incident HF, independent of established risk factors and inflammatory markers. However, undiagnosed HF at baseline may still be a confounder. There is a differential association between aspects of the frailty phenotype and incident HF.

Published
2021
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6. Active design of built environments for increasing levels of physical activity in adults: the ENABLE London natural experiment study

Author

Christopher G Owen, Elizabeth S Limb, Claire M Nightingale, Alicja R Rudnicka, Bina Ram, Aparna Shankar, Steven Cummins, Daniel Lewis, Christelle Clary, Ashley R Cooper, Angie S Page, Duncan Procter, Anne Ellaway, Billie Giles-Corti, Peter H Whincup, and Derek G Cook

Subjects
built environment, physical activity, adiposity, health behaviour, housing tenure, Public aspects of medicine, RA1-1270
Abstract

Background: Low physical activity is widespread and poses a serious public health challenge both globally and in the UK. The need to increase population levels of physical activity is recognised in current health policy recommendations. There is considerable interest in whether or not the built environment influences health behaviours, particularly physical activity levels, but longitudinal evidence is limited. Objectives: The effect of moving into East Village (the former London 2012 Olympic and Paralympic Games Athletes’ Village, repurposed on active design principles) on the levels of physical activity and adiposity, as well as other health-related and well-being outcomes among adults, was examined. Design: The Examining Neighbourhood Activities in Built Environments in London (ENABLE London) study was a longitudinal cohort study based on a natural experiment. Setting: East Village, London, UK. Participants: A cohort of 1278 adults (aged ≥ 16 years) and 219 children seeking to move into social, intermediate and market-rent East Village accommodation were recruited in 2013–15 and followed up after 2 years. Intervention: The East Village neighbourhood, the former London 2012 Olympic and Paralympic Games Athletes’ Village, is a purpose-built, mixed-use residential development specifically designed to encourage healthy active living by improving walkability and access to public transport. Main outcome measure: Change in objectively measured daily steps from baseline to follow-up. Methods: Change in environmental exposures associated with physical activity was assessed using Geographic Information System-derived measures. Individual objective measures of physical activity using accelerometry, body mass index and bioelectrical impedance (per cent of fat mass) were obtained, as were perceptions of change in crime and quality of the built environment. We examined changes in levels of physical activity and adiposity using multilevel models adjusting for sex, age group, ethnic group, housing sector (fixed effects) and baseline household (random effect), comparing the change in those who moved to East Village (intervention group) with the change in those who did not move to East Village (control group). Effects of housing sector (i.e. social, intermediate/affordable, market-rent) as an effect modifier were also examined. Qualitative work was carried out to provide contextual information about the perceived effects of moving to East Village. Results: A total of 877 adults (69%) were followed up after 2 years (mean 24 months, range 19–34 months, postponed from 1 year owing to the delayed opening of East Village), of whom 50% had moved to East Village; insufficient numbers of children moved to East Village to be considered further. In adults, moving to East Village was associated with only a small, non-significant, increase in mean daily steps (154 steps, 95% confidence interval –231 to 539 steps), more so in the intermediate sector (433 steps, 95% confidence interval –175 to 1042 steps) than in the social and market-rent sectors (although differences between housing sectors were not statistically significant), despite sizeable improvements in walkability, access to public transport and neighbourhood perceptions of crime and quality of the built environment. There were no appreciable effects on time spent in moderate to vigorous physical activity or sedentary time, body mass index or percentage fat mass, either overall or by housing sector. Qualitative findings indicated that, although participants enjoyed their new homes, certain design features might actually serve to reduce levels of activity. Conclusions: Despite strong evidence of large positive changes in neighbourhood perceptions and walkability, there was only weak evidence that moving to East Village was associated with increased physical activity. There was no evidence of an effect on markers of adiposity. Hence, improving the physical activity environment on its own may not be sufficient to increase population physical activity or other health behaviours. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 8, No. 12. See the NIHR Journals Library website for further project information. This research was also supported by project grants from the Medical Research Council National Prevention Research Initiative (MR/J000345/1).

Published
2020
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7. Weekend and weekday associations between the residential built environment and physical activity: Findings from the ENABLE London study.

Author

Christelle Clary, Daniel Lewis, Elizabeth S Limb, Claire M Nightingale, Bina Ram, Alicja R Rudnicka, Duncan Procter, Angie S Page, Ashley R Cooper, Anne Ellaway, Billie Giles-Corti, Peter H Whincup, Derek G Cook, Christopher G Owen, and Steven Cummins

Subjects
Medicine, Science
Abstract

BackgroundWe assessed whether the residential built environment was associated with physical activity (PA) differently on weekdays and weekends, and contributed to socio-economic differences in PA.MethodsMeasures of PA and walkability, park proximity and public transport accessibility were derived for baseline participants (n = 1,064) of the Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) Study. Multilevel-linear-regressions examined associations between weekend and weekday steps and Moderate to Vigorous PA (MVPA), residential built environment factors, and housing tenure status as a proxy for socio-economic position.ResultsA one-unit decrease in walkability was associated with 135 (95% CI [28; 242]) fewer steps and 1.2 (95% CI [0.3; 2.1]) fewer minutes of MVPA on weekend days, compared with little difference in steps and minutes of MVPA observed on weekdays. A 1km-increase in distance to the nearest local park was associated with 597 (95% CI [161; 1032]) more steps and 4.7 (95% CI [1.2; 8.2]) more minutes of MVPA on weekend days; 84 fewer steps (95% CI [-253;420]) and 0.3 fewer minutes of MVPA (95%CI [-2.3, 3.0]) on weekdays. Lower public transport accessibility was associated with increased steps on a weekday (767 steps, 95%CI [-13,1546]) compared with fewer steps on weekend days (608 fewer steps, 95% CI [-44, 1658]). None of the associations between built environment factors and PA on either weekend or weekdays were modified by socio-economic status. However, socio-economic differences in PA related moderately to socio-economic disparities in PA-promoting features of the residential neighbourhood.ConclusionsThe residential built environment is associated with PA differently at weekends and on weekdays, and contributes moderately to socio-economic differences in PA.

Published
2020
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8. The effect of moving to East Village, the former London 2012 Olympic and Paralympic Games Athletes' Village, on physical activity and adiposity (ENABLE London): a cohort study

Author

Claire M Nightingale, PhD, Elizabeth S Limb, MSc, Bina Ram, PhD, Aparna Shankar, PhD, Christelle Clary, PhD, Daniel Lewis, PhD, Steven Cummins, ProfPhD, Duncan Procter, PhD, Ashley R Cooper, ProfPhD, Angie S Page, ProfPhD, Anne Ellaway, ProfPhD, Billie Giles-Corti, ProfPhD, Peter H Whincup, ProfPhD, Alicja R Rudnicka, ProfPhD, Derek G Cook, ProfPhD, and Christopher G Owen, ProfPhD

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The built environment can affect health behaviours, but longitudinal evidence is limited. We aimed to examine the effect of moving into East Village, the former London 2012 Olympic and Paralympic Games Athletes' Village that was repurposed on active design principles, on adult physical activity and adiposity. Methods: In this cohort study, we recruited adults seeking new accommodation in East Village and compared physical activity and built environment measures with these data in control participants who had not moved to East Village. At baseline and after 2 years, we objectively measured physical activity with accelerometry and adiposity with body-mass index and bioimpedance, and we assessed objective measures of and participants' perceptions of change in their built environment. We examined the change in physical activity and adiposity between the East Village and control groups, after adjusting for sex, age group, ethnicity, housing tenure, and household (as a random effect). Findings: We recruited participants for baseline assessment between Jan 24, 2013, and Jan 7, 2016, and we followed up the cohort after 2 years, between Feb 24, 2015, and Oct 24, 2017. At baseline, 1819 households (one adult per household) consented to initial contact by the study team. 1278 adults (16 years and older) from 1006 (55%) households participated at baseline; of these participants, 877 (69%) adults from 710 (71%) households were assessed after 2 years, of whom 441 (50%) participants from 343 (48%) households had moved to East Village. We found no effect associated with moving to East Village on daily steps, the time spent doing moderate-to-vigorous physical activity (either in total or in 10-min bouts or more), daily sedentary time, body-mass index, or fat mass percentage between participants who had moved to East Village and those in the control group, despite sizeable improvements in walkability and neighbourhood perceptions of crime and quality among the East Village group relative to their original neighbourhood at baseline. Interpretation: Despite large improvements in neighbourhood perceptions and walkability, we found no clear evidence that moving to East Village was associated with increased physical activity. Improving the built environment on its own might be insufficient to increase physical activity. Funding: National Institute for Health Research and National Prevention Research Initiative.

Published
2019
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9. Physical activity levels in adults and older adults 3-4 years after pedometer-based walking interventions: Long-term follow-up of participants from two randomised controlled trials in UK primary care.

Author

Tess Harris, Sally M Kerry, Elizabeth S Limb, Cheryl Furness, Charlotte Wahlich, Christina R Victor, Steve Iliffe, Peter H Whincup, Michael Ussher, Ulf Ekelund, Julia Fox-Rushby, Judith Ibison, Stephen DeWilde, Cathy McKay, and Derek G Cook

Subjects
Medicine
Abstract

BackgroundPhysical inactivity is an important cause of noncommunicable diseases. Interventions can increase short-term physical activity (PA), but health benefits require maintenance. Few interventions have evaluated PA objectively beyond 12 months. We followed up two pedometer interventions with positive 12-month effects to examine objective PA levels at 3-4 years.Methods and findingsLong-term follow-up of two completed trials: Pedometer And Consultation Evaluation-UP (PACE-UP) 3-arm (postal, nurse support, control) at 3 years and Pedometer Accelerometer Consultation Evaluation-Lift (PACE-Lift) 2-arm (nurse support, control) at 4 years post-baseline. Randomly selected patients from 10 United Kingdom primary care practices were recruited (PACE-UP: 45-75 years, PACE-Lift: 60-75 years). Intervention arms received 12-week walking programmes (pedometer, handbooks, PA diaries) postally (PACE-UP) or with nurse support (PACE-UP, PACE-Lift). Main outcomes were changes in 7-day accelerometer average daily step counts and weekly time in moderate-to-vigorous PA (MVPA) in ≥10-minute bouts in intervention versus control groups, between baseline and 3 years (PACE-UP) and 4 years (PACE-Lift). PACE-UP 3-year follow-up was 67% (681/1,023) (mean age: 59, 64% female), and PACE-Lift 4-year follow-up was 76% (225/298) (mean age: 67, 53% female). PACE-UP 3-year intervention versus control comparisons were as follows: additional steps/day postal +627 (95% CI: 198-1,056), p = 0.004, nurse +670 (95% CI: 237-1,102), p = 0.002; total weekly MVPA in bouts (minutes/week) postal +28 (95% CI: 7-49), p = 0.009, nurse +24 (95% CI: 3-45), p = 0.03. PACE-Lift 4-year intervention versus control comparisons were: +407 (95% CI: -177-992), p = 0.17 steps/day, and +32 (95% CI: 5-60), p = 0.02 minutes/week MVPA in bouts. Neither trial showed sedentary or wear-time differences. Main study limitation was incomplete follow-up; however, results were robust to missing data sensitivity analyses.ConclusionsIntervention participants followed up from both trials demonstrated higher levels of objectively measured PA at 3-4 years than controls, similar to previously reported 12-month trial effects. Pedometer interventions, delivered by post or with nurse support, can help address the public health physical inactivity challenge.Trial registrationsPACE-UP isrctn.com ISRCTN98538934; PACE-Lift isrctn.com ISRCTN42122561.

Published
2018
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10. Effect of a Primary Care Walking Intervention with and without Nurse Support on Physical Activity Levels in 45- to 75-Year-Olds: The Pedometer And Consultation Evaluation (PACE-UP) Cluster Randomised Clinical Trial.

Author

Tess Harris, Sally M Kerry, Elizabeth S Limb, Christina R Victor, Steve Iliffe, Michael Ussher, Peter H Whincup, Ulf Ekelund, Julia Fox-Rushby, Cheryl Furness, Nana Anokye, Judith Ibison, Steve DeWilde, Lee David, Emma Howard, Rebecca Dale, Jaime Smith, and Derek G Cook

Subjects
Medicine
Abstract

BackgroundPedometers can increase walking and moderate-to-vigorous physical activity (MVPA) levels, but their effectiveness with or without support has not been rigorously evaluated. We assessed the effectiveness of a pedometer-based walking intervention in predominantly inactive adults, delivered by post or through primary care nurse-supported physical activity (PA) consultations.Methods and findingsA parallel three-arm cluster randomised trial was randomised by household, with 12-mo follow-up, in seven London, United Kingdom, primary care practices. Eleven thousand fifteen randomly selected patients aged 45-75 y without PA contraindications were invited. Five hundred forty-eight self-reporting achieving PA guidelines were excluded. One thousand twenty-three people from 922 households were randomised between 2012-2013 to one of the following groups: usual care (n = 338); postal pedometer intervention (n = 339); and nurse-supported pedometer intervention (n = 346). Of these, 956 participants (93%) provided outcome data (usual care n = 323, postal n = 312, nurse-supported n = 321). Both intervention groups received pedometers, 12-wk walking programmes, and PA diaries. The nurse group was offered three PA consultations. Primary and main secondary outcomes were changes from baseline to 12 mo in average daily step-counts and time in MVPA (in ≥10-min bouts), respectively, measured objectively by accelerometry. Only statisticians were masked to group. Analysis was by intention-to-treat. Average baseline daily step-count was 7,479 (standard deviation [s.d.] 2,671), and average time in MVPA bouts was 94 (s.d. 102) min/wk. At 12 mo, mean steps/d, with s.d. in parentheses, were as follows: control 7,246 (2,671); postal 8,010 (2,922); and nurse support 8,131 (3,228). PA increased in both intervention groups compared with the control group; additional steps/d were 642 for postal (95% CI 329-955) and 677 for nurse support (95% CI 365-989); additional MVPA in bouts (min/wk) were 33 for postal (95% CI 17-49) and 35 for nurse support (95% CI 19-51). There were no significant differences between the two interventions at 12 mo. The 10% (1,023/10,467) recruitment rate was a study limitation.ConclusionsA primary care pedometer-based walking intervention in predominantly inactive 45- to 75-y-olds increased step-counts by about one-tenth and time in MVPA in bouts by about one-third. Nurse and postal delivery achieved similar 12-mo PA outcomes. A primary care pedometer intervention delivered by post or with minimal support could help address the public health physical inactivity challenge.Clinical trial registrationisrctn.com ISRCTN98538934.

Published
2017
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11. Challenges in Collating Spirometry Reference Data for South-Asian Children: An Observational Study.

Author

Sooky Lum, Vassiliki Bountziouka, Philip Quanjer, Samatha Sonnappa, Angela Wade, Caroline Beardsmore, Sunil K Chhabra, Rajesh K Chudasama, Derek G Cook, Seeromanie Harding, Claudia E Kuehni, K V V Prasad, Peter H Whincup, Simon Lee, and Janet Stocks

Subjects
Medicine, Science
Abstract

MethodsSpirometry datasets from South-Asian children were collated from four centres in India and five within the UK. Records with transcription errors, missing values for height or spirometry, and implausible values were excluded(n = 110).ResultsFollowing exclusions, cross-sectional data were available from 8,124 children (56.3% male; 5-17 years). When compared with GLI-predicted values from White Europeans, forced expired volume in 1s (FEV1) and forced vital capacity (FVC) in South-Asian children were on average 15% lower, ranging from 4-19% between centres. By contrast, proportional reductions in FEV1 and FVC within all but two datasets meant that the FEV1/FVC ratio remained independent of ethnicity. The 'GLI-Other' equation fitted data from North India reasonably well while 'GLI-Black' equations provided a better approximation for South-Asian data than the 'GLI-White' equation. However, marked discrepancies in the mean lung function z-scores between centres especially when examined according to socio-economic conditions precluded derivation of a single South-Asian GLI-adjustment.ConclusionUntil improved and more robust prediction equations can be derived, we recommend the use of 'GLI-Black' equations for interpreting most South-Asian data, although 'GLI-Other' may be more appropriate for North Indian data. Prospective data collection using standardised protocols to explore potential sources of variation due to socio-economic circumstances, secular changes in growth/predictors of lung function and ethnicities within the South-Asian classification are urgently required.

Published
2016
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12. A primary care nurse-delivered walking intervention in older adults: PACE (pedometer accelerometer consultation evaluation)-Lift cluster randomised controlled trial.

Author

Tess Harris, Sally M Kerry, Christina R Victor, Ulf Ekelund, Alison Woodcock, Steve Iliffe, Peter H Whincup, Carole Beighton, Michael Ussher, Elizabeth S Limb, Lee David, Debbie Brewin, Fredrika Adams, Annabelle Rogers, and Derek G Cook

Subjects
Medicine
Abstract

BackgroundBrisk walking in older people can increase step-counts and moderate to vigorous intensity physical activity (MVPA) in ≥10-minute bouts, as advised in World Health Organization guidelines. Previous interventions have reported step-count increases, but not change in objectively measured MVPA in older people. We assessed whether a primary care nurse-delivered complex intervention increased objectively measured step-counts and MVPA.Methods and findingsA total of 988 60-75 year olds, able to increase walking and randomly selected from three UK family practices, were invited to participate in a parallel two-arm cluster randomised trial; randomisation was by household. Two-hundred-ninety-eight people from 250 households were randomised between 2011 and 2012; 150 individuals to the intervention group, 148 to the usual care control group. Intervention participants received four primary care nurse physical activity (PA) consultations over 3 months, incorporating behaviour change techniques, pedometer step-count and accelerometer PA intensity feedback, and an individual PA diary and plan. Assessors were not blinded to group status, but statistical analyses were conducted blind. The primary outcome was change in accelerometry assessed average daily step-counts between baseline and 3 months, with change at 12 months a secondary outcome. Other secondary outcomes were change from baseline in time in MVPA weekly in ≥10-minute bouts, accelerometer counts, and counts/minute at 3 months and 12 months. Other outcomes were adverse events, anthropometric measures, mood, and pain. Qualitative evaluations of intervention participants and practice nurses assessed the intervention's acceptability. At 3 months, eight participants had withdrawn or were lost to follow-up, 280 (94%) individuals provided primary outcome data. At 3 months changes in both average daily step-counts and weekly MVPA in ≥10-minute bouts were significantly higher in the intervention than control group: by 1,037 (95% CI 513-1,560) steps/day and 63 (95% CI 40-87) minutes/week, respectively. At 12 months corresponding differences were 609 (95% CI 104-1,115) steps/day and 40 (95% CI 17-63) minutes/week. Counts and counts/minute showed similar effects to steps and MVPA. Adverse events, anthropometry, mood, and pain were similar in the two groups. Participants and practice nurses found the intervention acceptable and enjoyable.ConclusionsThe PACE-Lift trial increased both step-counts and objectively measured MVPA in ≥10-minute bouts in 60-75 year olds at 3 and 12 months, with no effect on adverse events. To our knowledge, this is the first trial in this age group to demonstrate objective MVPA increases and highlights the value of individualised support incorporating objective PA assessment in a primary care setting.Trial registrationControlled-Trials.com ISRCTN42122561.

Published
2015
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13. Long-Term Exposure to Primary Traffic Pollutants and Lung Function in Children: Cross-Sectional Study and Meta-Analysis.

Author

Francesco Barone-Adesi, Jennifer E Dent, David Dajnak, Sean Beevers, H Ross Anderson, Frank J Kelly, Derek G Cook, and Peter H Whincup

Subjects
Medicine, Science
Abstract

BACKGROUND:There is widespread concern about the possible health effects of traffic-related air pollution. Nitrogen dioxide (NO2) is a convenient marker of primary pollution. We investigated the associations between lung function and current residential exposure to a range of air pollutants (particularly NO2, NO, NOx and particulate matter) in London children. Moreover, we placed the results for NO2 in context with a meta-analysis of published estimates of the association. METHODS AND FINDINGS:Associations between primary traffic pollutants and lung function were investigated in 4884 children aged 9-10 years who participated in the Child Heart and Health Study in England (CHASE). A systematic literature search identified 13 studies eligible for inclusion in a meta-analysis. We combined results from the meta-analysis with the distribution of the values of FEV1 in CHASE to estimate the prevalence of children with abnormal lung function (FEV1

Published
2015
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14. Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

Author

Amy E Taylor, Richard W Morris, Meg E Fluharty, Johan H Bjorngaard, Bjørn Olav Åsvold, Maiken E Gabrielsen, Archie Campbell, Riccardo Marioni, Meena Kumari, Jenni Hällfors, Satu Männistö, Pedro Marques-Vidal, Marika Kaakinen, Alana Cavadino, Iris Postmus, Lise Lotte N Husemoen, Tea Skaaby, Tarunveer S Ahluwalia, Jorien L Treur, Gonneke Willemsen, Caroline Dale, S Goya Wannamethee, Jari Lahti, Aarno Palotie, Katri Räikkönen, Aliaksei Kisialiou, Alex McConnachie, Sandosh Padmanabhan, Andrew Wong, Christine Dalgård, Lavinia Paternoster, Yoav Ben-Shlomo, Jessica Tyrrell, John Horwood, David M Fergusson, Martin A Kennedy, Tim Frayling, Ellen A Nohr, Lene Christiansen, Kirsten Ohm Kyvik, Diana Kuh, Graham Watt, Johan Eriksson, Peter H Whincup, Jacqueline M Vink, Dorret I Boomsma, George Davey Smith, Debbie Lawlor, Allan Linneberg, Ian Ford, J Wouter Jukema, Christine Power, Elina Hyppönen, Marjo-Riitta Jarvelin, Martin Preisig, Katja Borodulin, Jaakko Kaprio, Mika Kivimaki, Blair H Smith, Caroline Hayward, Pål R Romundstad, Thorkild I A Sørensen, Marcus R Munafò, and Naveed Sattar

Subjects
Genetics, QH426-470
Abstract

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Published
2014
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15. Regular breakfast consumption and type 2 diabetes risk markers in 9- to 10-year-old children in the child heart and health study in England (CHASE): a cross-sectional analysis.

Author

Angela S Donin, Claire M Nightingale, Chris G Owen, Alicja R Rudnicka, Michael R Perkin, Susan A Jebb, Alison M Stephen, Naveed Sattar, Derek G Cook, and Peter H Whincup

Subjects
Medicine
Abstract

BACKGROUND:Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children. METHODS AND FINDINGS:We conducted a cross-sectional study of 4,116 UK primary school children aged 9-10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%-37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%-37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%-2.0%), glucose (percent difference 1.0%, 95% CI 0.0%-2.0%), and urate (percent difference 6%, 95% CI 3%-10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity

Published
2014
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16. Adiposity in early, middle and later adult life and cardiometabolic risk markers in later life; findings from the British regional heart study.

Author

Venediktos V Kapetanakis, Alicja R Rudnicka, Andrea K Wathern, Lucy Lennon, Olia Papacosta, Derek G Cook, S Goya Wannamethee, Peter H Whincup, and Christopher G Owen

Subjects
Medicine, Science
Abstract

This research investigates the associations between body mass index (BMI) at 21, 40-59, 60-79 years of age on cardiometabolic risk markers at 60-79 years.A prospective study of 3464 British men with BMI measured at 40-59 and 60-79 years, when cardiometabolic risk was assessed. BMI at 21 years was ascertained from military records, or recalled from middle-age (adjusted for reporting bias); associations between BMI at different ages and later cardiometabolic risk markers were examined using linear regression. Sensitive period, accumulation and mobility life course models were devised for high BMI (defined as BMI≥75th centile) and compared with a saturated BMI trajectory model.At ages 21, 40-59 and 60-79 years, prevalences of overweight (BMI≥25 kg/m2) were 12%, 53%, 70%, and obesity (≥30 kg/m2) 1.6%, 6.6%, and 17.6%, respectively. BMI at 21 years was positively associated with serum insulin, blood glucose, and HbA1c at 60-79 years, with increases of 1.5% (95%CI 0.8,2.3%), 0.4% (0.1,0.6%), 0.3% (0.1,0.4%) per 1 kg/m2, respectively, but showed no associations with blood pressure or blood cholesterol. However, these associations were modest compared to those between BMI at 60-79 years and serum insulin, blood glucose and HbA1c at 60-79 years, with increases of 8.6% (8.0,9.2%), 0.7% (0.5,0.9%), and 0.5% (0.4,0.7%) per 1 kg/m2, respectively. BMI at 60-79 years was also associated with total cholesterol and blood pressure. Associations for BMI at 40-59 years were mainly consistent with those of BMI at 60-79 years. None of the life course models fitted the data as well as the saturated model for serum insulin. A sensitive period at 50 years for glucose and HbA1c and sensitive period at 70 years for blood pressure were identified.In this cohort of men who were thin compared to more contemporary cohorts, BMI in later life was the dominant influence on cardiovascular and diabetes risk. BMI in early adult life may have a small long-term effect on diabetes risk.

Published
2014
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17. Are ethnic and gender specific equations needed to derive fat free mass from bioelectrical impedance in children of South asian, black african-Caribbean and white European origin? Results of the assessment of body composition in children study.

Author

Claire M Nightingale, Alicja R Rudnicka, Christopher G Owen, Angela S Donin, Sian L Newton, Cheryl A Furness, Emma L Howard, Rachel D Gillings, Jonathan C K Wells, Derek G Cook, and Peter H Whincup

Subjects
Medicine, Science
Abstract

Bioelectrical impedance analysis (BIA) is a potentially valuable method for assessing lean mass and body fat levels in children from different ethnic groups. We examined the need for ethnic- and gender-specific equations for estimating fat free mass (FFM) from BIA in children from different ethnic groups and examined their effects on the assessment of ethnic differences in body fat.Cross-sectional study of children aged 8-10 years in London Primary schools including 325 South Asians, 250 black African-Caribbeans and 289 white Europeans with measurements of height, weight and arm-leg impedance (Z; Bodystat 1500). Total body water was estimated from deuterium dilution and converted to FFM. Multilevel models were used to derive three types of equation {A: FFM = linear combination(height+weight+Z); B: FFM = linear combination(height(2)/Z); C: FFM = linear combination(height(2)/Z+weight)}.Ethnicity and gender were important predictors of FFM and improved model fit in all equations. The models of best fit were ethnicity and gender specific versions of equation A, followed by equation C; these provided accurate assessments of ethnic differences in FFM and FM. In contrast, the use of generic equations led to underestimation of both the negative South Asian-white European FFM difference and the positive black African-Caribbean-white European FFM difference (by 0.53 kg and by 0.73 kg respectively for equation A). The use of generic equations underestimated the positive South Asian-white European difference in fat mass (FM) and overestimated the positive black African-Caribbean-white European difference in FM (by 4.7% and 10.1% respectively for equation A). Consistent results were observed when the equations were applied to a large external data set.Ethnic- and gender-specific equations for predicting FFM from BIA provide better estimates of ethnic differences in FFM and FM in children, while generic equations can misrepresent these ethnic differences.

Published
2013
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18. Travel to school and physical activity levels in 9-10 year-old UK children of different ethnic origin; Child Heart and Health Study in England (CHASE).

Author

Christopher G Owen, Claire M Nightingale, Alicja R Rudnicka, Esther M F van Sluijs, Ulf Ekelund, Derek G Cook, and Peter H Whincup

Subjects
Medicine, Science
Abstract

Travel to school may offer a convenient way to increase physical activity levels in childhood. We examined the association between method of travel to school and physical activity levels in urban multi-ethnic children.2035 children (aged 9-10 years in 2006-7) provided data on their usual method of travel to school and wore an Actigraph-GT1M activity monitor during waking hours. Associations between method of travel and mean level of physical activity (counts per minute [CPM], steps, time spent in light, moderate or vigorous activity per day) were examined in models adjusted for confounding variables. 1393 children (69%) walked or cycled to school; 161 (8%) used public transport and 481 (24%) travelled by car. White European children were more likely to walk/cycle, black African Caribbeans to travel by public transport and South Asian children to travel by car. Children travelling by car spent less time in moderate to vigorous physical activity (-7 mins, 95%CI-9,-5), and had lower CPM (-32 CPM, 95%CI-44,-19) and steps per day (-813 steps, 95%CI,-1043,-582) than walkers/cyclists. Pupils travelling by public transport had similar activity levels to walkers/cyclists. Lower physical activity levels amongst car travellers' were especially marked at travelling times (school days between 8-9 am, 3-5 pm), but were also evident on weekdays at other times and at weekends; they did not differ by gender or ethnic group.Active travel to school is associated with higher levels of objectively measured physical activity, particularly during periods of travel but also at other times. If children travelling by car were to achieve physical activity levels (steps) similar to children using active travel, they would increase their physical activity levels by 9%. However, the population increase would be a modest 2%, because of the low proportion of car travellers in this urban population.

Published
2012
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19. Cardiometabolic risk markers in Indian children: comparison with UK Indian and white European children.

Author

Claire M Nightingale, Ghattu V Krishnaveni, Alicja R Rudnicka, Christopher G Owen, Sargoor R Veena, Jacqueline C Hill, Derek G Cook, Caroline H D Fall, and Peter H Whincup

Subjects
Medicine, Science
Abstract

OBJECTIVE:UK Indian adults have higher risks of coronary heart disease and type 2 diabetes than Indian and UK European adults. With growing evidence that these diseases originate in early life, we compared cardiometabolic risk markers in Indian, UK Indian and white European children. METHODS:Comparisons were based on the Mysore Parthenon Birth Cohort Study (MPBCS), India and the Child Heart Health Study in England (CHASE), which studied 9-10 year-old children (538 Indian, 483 UK Indian, 1375 white European) using similar methods. Analyses adjusted for study differences in age and sex. RESULTS:Compared with Mysore Indians, UK Indians had markedly higher BMI (% difference 21%, 95%CI 18 to 24%), skinfold thickness (% difference 34%, 95%CI 26 to 42%), LDL-cholesterol (mean difference 0.48, 95%CI 0.38 to 0.57 mmol/L), systolic BP (mean difference 10.3, 95% CI 8.9 to 11.8 mmHg) and fasting insulin (% difference 145%, 95%CI 124 to 168%). These differences (similar in both sexes and little affected by adiposity adjustment) were larger than those between UK Indians and white Europeans. Compared with white Europeans, UK Indians had higher skinfold thickness (% difference 6.0%, 95%CI 1.5 to 10.7%), fasting insulin (% difference 31%, 95%CI 22 to 40%), triglyceride (% difference 13%, 95%CI 8 to 18%) and LDL-cholesterol (mean difference 0.12 mmol/L, 95%CI 0.04 to 0.19 mmol/L). CONCLUSIONS:UK Indian children have an adverse cardiometabolic risk profile, especially compared to Indian children. These differences, not simply reflecting greater adiposity, emphasize the need for prevention strategies starting in childhood or earlier.

Published
2012
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20. Socio-economic position and type 2 diabetes risk factors: patterns in UK children of South Asian, black African-Caribbean and white European origin.

Author

Claudia Thomas, Claire M Nightingale, Angela S Donin, Alicja R Rudnicka, Christopher G Owen, Naveed Sattar, Derek G Cook, and Peter H Whincup

Subjects
Medicine, Science
Abstract

BACKGROUND:Socio-economic position (SEP) and ethnicity influence type 2 diabetes mellitus (T2DM) risk in adults. However, the influence of SEP on emerging T2DM risks in different ethnic groups and the contribution of SEP to ethnic differences in T2DM risk in young people have been little studied. We examined the relationships between SEP and T2DM risk factors in UK children of South Asian, black African-Caribbean and white European origin, using the official UK National Statistics Socio-economic Classification (NS-SEC) and assessed the extent to which NS-SEC explained ethnic differences in T2DM risk factors. METHODS AND FINDINGS:Cross-sectional school-based study of 4,804 UK children aged 9-10 years, including anthropometry and fasting blood analytes (response rates 70%, 68% and 58% for schools, individuals and blood measurements). Assessment of SEP was based on parental occupation defined using NS-SEC and ethnicity on parental self-report. Associations between NS-SEC and adiposity, insulin resistance (IR) and triglyceride differed between ethnic groups. In white Europeans, lower NS-SEC status was related to higher ponderal index (PI), fat mass index, IR and triglyceride (increases per NS-SEC decrement [95%CI] were 1.71% [0.75, 2.68], 4.32% [1.24, 7.48], 5.69% [2.01, 9.51] and 3.17% [0.96, 5.42], respectively). In black African-Caribbeans, lower NS-SEC was associated with lower PI (-1.12%; [-2.01, -0.21]), IR and triglyceride, while in South Asians there were no consistent associations between NS-SEC and T2DM risk factors. Adjustment for NS-SEC did not appear to explain ethnic differences in T2DM risk factors, which were particularly marked in high NS-SEC groups. CONCLUSIONS:SEP is associated with T2DM risk factors in children but patterns of association differ by ethnic groups. Consequently, ethnic differences (which tend to be largest in affluent socio-economic groups) are not explained by NS-SEC. This suggests that strategies aimed at reducing social inequalities in T2DM risk are unlikely to reduce emerging ethnic differences in T2DM risk.

Published
2012
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21. Social class differences in secular trends in established coronary risk factors over 20 years: a cohort study of British men from 1978-80 to 1998-2000.

Author

Sheena E Ramsay, Peter H Whincup, Sarah L Hardoon, Lucy T Lennon, Richard W Morris, and S G Wannamethee

Subjects
Medicine, Science
Abstract

BACKGROUND:Coronary heart disease (CHD) mortality in the UK since the late 1970s has declined more markedly among higher socioeconomic groups. However, little is known about changes in coronary risk factors in different socioeconomic groups. This study examined whether changes in established coronary risk factors in Britain over 20 years between 1978-80 and 1998-2000 differed between socioeconomic groups. METHODS AND FINDINGS:A socioeconomically representative cohort of 7735 British men aged 40-59 years was followed-up from 1978-80 to 1998-2000; data on blood pressure (BP), cholesterol, body mass index (BMI) and cigarette smoking were collected at both points in 4252 survivors. Social class was based on longest-held occupation in middle-age. Compared with men in non-manual occupations, men in manual occupations experienced a greater increase in BMI (mean difference = 0.33 kg/m(2); 95%CI 0.14-0.53; p for interaction = 0.001), a smaller decline in non-HDL cholesterol (difference in mean change = 0.18 mmol/l; 95%CI 0.11-0.25, p for interaction≤0.0001) and a smaller increase in HDL cholesterol (difference in mean change = 0.04 mmol/l; 95%CI 0.02-0.06, p for interaction≤0.0001). However, mean systolic BP declined more in manual than non-manual groups (difference in mean change = 3.6; 95%CI 2.1-5.1, p for interaction≤0.0001). The odds of being a current smoker in 1978-80 and 1998-2000 did not differ between non-manual and manual social classes (p for interaction = 0.51). CONCLUSION:Several key risk factors for CHD and type 2 diabetes showed less favourable changes in men in manual occupations. Continuing priority is needed to improve adverse cardiovascular risk profiles in socially disadvantaged groups in the UK.

Published
2011
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22. Early emergence of ethnic differences in type 2 diabetes precursors in the UK: the Child Heart and Health Study in England (CHASE Study).

Author

Peter H Whincup, Claire M Nightingale, Christopher G Owen, Alicja R Rudnicka, Ian Gibb, Catherine M McKay, Angela S Donin, Naveed Sattar, K George M M Alberti, and Derek G Cook

Subjects
Medicine
Abstract

Adults of South Asian origin living in the United Kingdom have high risks of type 2 diabetes and central obesity; raised circulating insulin, triglyceride, and C-reactive protein concentrations; and low HDL-cholesterol when compared with white Europeans. Adults of African-Caribbean origin living in the UK have smaller increases in type 2 diabetes risk, raised circulating insulin and HDL-cholesterol, and low triglyceride and C-reactive protein concentrations. We examined whether corresponding ethnic differences were apparent in childhood.We performed a cross-sectional survey of 4,796 children aged 9-10 y in three UK cities who had anthropometric measurements (68% response) and provided blood samples (58% response); ethnicity was based on parental definition. In age-adjusted comparisons with white Europeans (n = 1,153), South Asian children (n = 1,306) had higher glycated haemoglobin (HbA1c) (% difference: 2.1, 95% CI 1.6 to 2.7), fasting insulin (% difference 30.0, 95% CI 23.4 to 36.9), triglyceride (% difference 12.9, 95% CI 9.4 to 16.5), and C-reactive protein (% difference 43.3, 95% CI 28.6 to 59.7), and lower HDL-cholesterol (% difference -2.9, 95% CI -4.5 to -1.3). Higher adiposity levels among South Asians (based on skinfolds and bioimpedance) did not account for these patterns. Black African-Caribbean children (n = 1,215) had higher levels of HbA1c, insulin, and C-reactive protein than white Europeans, though the ethnic differences were not as marked as in South Asians. Black African-Caribbean children had higher HDL-cholesterol and lower triglyceride levels than white Europeans; adiposity markers were not increased.Ethnic differences in type 2 diabetes precursors, mostly following adult patterns, are apparent in UK children in the first decade. Some key determinants operate before adult life and may provide scope for early prevention.

Published
2010
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23. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.

Author

John Danesh, Stephen Kaptoge, Andrea G Mann, Nadeem Sarwar, Angela Wood, Sara B Angleman, Frances Wensley, Julian P T Higgins, Lucy Lennon, Gudny Eiriksdottir, Ann Rumley, Peter H Whincup, Gordon D O Lowe, and Vilmundur Gudnason

Subjects
Medicine
Abstract

BackgroundThe relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context.Methods and findingsMeasurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual") IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels).ConclusionsLong-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CHD.

Published
2008
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24. Evaluating Ethnic Variations in the Risk of Infections in People With Prediabetes and Type 2 Diabetes: A Matched Cohort Study

Author

Iain M. Carey, Julia A. Critchley, Umar A.R. Chaudhry, Stephen DeWilde, Elizabeth S. Limb, Derek G. Cook, Peter H. Whincup, and Tess Harris

Subjects
Advanced and Specialized Nursing, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

OBJECTIVE People living with type 2 diabetes (T2D) are at higher infection risk, but it is unknown how this risk varies by ethnicity or whether the risk is similarly observed in people with nondiabetic hyperglycemia (“prediabetes”). RESEARCH DESIGN AND METHODS We included 527,151 patients in England with T2D and 273,216 with prediabetes, aged 18–90, and alive on 1 January 2015 on the Clinical Practice Research Datalink. Each was matched to two patients without diabetes or prediabetes on age, sex, and ethnic group. Infections during 2015–2019 were collated from primary care and linked hospitalization records. Infection incidence rate ratios (IRRs) for those with prediabetes or T2D were estimated, unadjusted and adjusted for confounders. RESULTS People with T2D had increased risk for infections presenting in primary care (IRR 1.51, 95% CI 1.51–1.52) and hospitalizations (IRR 1.91, 1.90–1.93). This was broadly consistent overall within each ethnic group, although younger White T2D patients (age CONCLUSIONS The elevated infection risk for people with T2D appears similar for different ethnic groups and is also seen in people with prediabetes. Infections are a substantial cause of ill-health and health service use for people with prediabetes and T2D. This has public health implications with rising prediabetes and diabetes prevalence.

Published
2023

25. Retinal microvascular associations with cardiometabolic risk factors differ by diabetes status: results from the UK Biobank

Author

Robyn J, Tapp, Christopher G, Owen, Sarah A, Barman, David P, Strachan, Roshan A, Welikala, Paul J, Foster, Peter H, Whincup, and Alicja R, Rudnicka

Subjects
Arterioles, C-Reactive Protein, Cholesterol, Risk Factors, Endocrinology, Diabetes and Metabolism, Diabetes Mellitus, Internal Medicine, Cardiometabolic Risk Factors, Humans, Retinal Vessels, Blood Pressure, United Kingdom, Biological Specimen Banks
Abstract

Aims/hypothesis The aim of the study was to examine the association of retinal vessel morphometry with BP, body composition and biochemistry, and to determine whether these associations differ by diabetes status. Methods The UK Biobank ocular assessment included 68,550 participants aged 40-70 years who underwent non-mydriatic retinal photography, BP and body composition measurements, and haematological analysis. A fully automated image analysis program provided measurements of retinal vessel diameter and tortuosity. The associations between retinal vessel morphology and cardiometabolic risk factors by diabetes status were examined using multilevel linear regression, to provide absolute differences in vessel diameter and percentage differences in tortuosity (allowing for within-person clustering). Results A total of 50,233 participants (a reduction from 68,550) were included in these analyses. Overall, those with diabetes had significantly more tortuous venules and wider arteriolar diameters compared with those without. Associations between venular tortuosity and cardiometabolic risk factors differed according to diabetes status (p interaction 1c, C-reactive protein, white cell count and granulocyte count. For example, a unit rise in white cell count was associated with a 0.18% increase (95% CI 0.05, 0.32%) in venular tortuosity for those without diabetes and a 1.48% increase (95% CI 0.90, 2.07%) among those with diabetes. For arteriolar diameter, significant interactions were evident for systolic BP, diastolic BP, mean arterial pressure (MAP) and LDL-cholesterol. For example, a 10 mmHg rise in systolic BP was associated with a −0.92 μm difference (95% CI −0.96 to −0.88 μm) in arteriolar diameter for those without diabetes, and a −0.58 μm difference (95% CI −0.76 to −0.41 μm) among those with diabetes. No interactions were observed for arteriolar tortuosity or venular diameters. Conclusions/interpretation We provide clear evidence of the modifying effect of diabetes on cardiometabolic risk factor associations with retinal microvascular architecture. These observations suggest the occurrence of preclinical disease processes, and may be a sign of impaired autoregulation due to hyperglycaemia, which has been suggested to play a pivotal role in the development of diabetes-related microvascular complications. Data Availability The data supporting the results reported here are available through the UK Biobank (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). Graphical abstract

Published
2022

26. Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis

Author

Amanda E, Paluch, Shivangi, Bajpai, Marcel, Ballin, David R, Bassett, Thomas W, Buford, Mercedes R, Carnethon, Ariel, Chernofsky, Erin E, Dooley, Ulf, Ekelund, Kelly R, Evenson, Deborah A, Galuska, Barbara J, Jefferis, Lingsong, Kong, William E, Kraus, Martin G, Larson, I-Min, Lee, Charles E, Matthews, Robert L, Newton, Anna, Nordström, Peter, Nordström, Priya, Palta, Alpa V, Patel, Kelley, Pettee Gabriel, Carl F, Pieper, Lisa, Pompeii, Erika, Rees-Punia, Nicole L, Spartano, Ramachandran S, Vasan, Peter H, Whincup, Shengping, Yang, and Janet E, Fulton

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Taking fewer than the widely promoted “10 000 steps per day” has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose–response relationship between steps per day and CVD can help inform clinical and public health guidelines. Methods: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance–weighted random effects models. Results: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, Conclusions: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician–patient communication and population health to reduce the risk of CVD.

Published
2022

29. Device-measured physical activity, adiposity and mortality: a harmonised meta-analysis of eight prospective cohort studies

Author

Jakob Tarp, Morten W Fagerland, Knut Eirik Dalene, Jostein Steene Johannessen, Bjørge H Hansen, Barbara J Jefferis, Peter H Whincup, Keith M Diaz, Steven Hooker, Virginia J Howard, Ariel Chernofsky, Martin G Larson, Nicole L Spartano, Ramachandran S Vasan, Ing-Mari Dohrn, Maria Hagströmer, Charlotte Edwardson, Thomas Yates, Eric J Shiroma, Paddy C Dempsey, Katrien Wijndaele, Sigmund A Anderssen, I-Min Lee, Ulf Ekelund, Tarp, Jakob [0000-0002-9186-7077], Jefferis, Barbara J [0000-0002-0850-3177], Diaz, Keith M [0000-0003-0190-0548], Dohrn, Ing-Mari [0000-0003-2593-550X], Yates, Thomas [0000-0002-5724-5178], Dempsey, Paddy C [0000-0002-1714-6087], Lee, I-Min [0000-0002-1083-6907], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, exercise, Original research, Physical Therapy, Sports Therapy and Rehabilitation, body mass index, General Medicine, Middle Aged, Overweight, VDP::Medisinske Fag: 700::Idrettsmedisinske fag: 850, Cohort Studies, VDP::Medisinske Fag: 700::Helsefag: 800, Risk Factors, Humans, Orthopedics and Sports Medicine, observational study, Female, Obesity, Prospective Studies, Waist Circumference, Adiposity
Abstract

BackgroundThe joint associations of total and intensity-specific physical activity with obesity in relation to all-cause mortality risk are unclear.MethodsWe included 34 492 adults (72% women, median age 62.1 years, 2034 deaths during follow-up) in a harmonised meta-analysis of eight population-based prospective cohort studies with mean follow-up ranging from 6.0 to 14.5 years. Standard body mass index categories were cross-classified with sample tertiles of device-measured total, light-to-vigorous and moderate-to-vigorous physical activity and sedentary time. In five cohorts with waist circumference available, high and low waist circumference was combined with tertiles of moderate-to-vigorous physical activity.ResultsThere was an inverse dose–response relationship between higher levels of total and intensity-specific physical activity and mortality risk in those who were normal weight and overweight. In individuals with obesity, the inverse dose–response relationship was only observed for total physical activity. Similarly, lower levels of sedentary time were associated with lower mortality risk in normal weight and overweight individuals but there was no association between sedentary time and risk of mortality in those who were obese. Compared with the obese-low total physical activity reference, the HRs were 0.59 (95% CI 0.44 to 0.79) for normal weight-high total activity and 0.67 (95% CI 0.48 to 0.94) for obese-high total activity. In contrast, normal weight-low total physical activity was associated with a higher risk of mortality compared with the obese-low total physical activity reference (1.28; 95% CI 0.99 to 1.67).ConclusionsHigher levels of physical activity were associated with lower risk of mortality irrespective of weight status. Compared with obesity-low physical activity, there was no survival benefit of being normal weight if physical activity levels were low.

Published
2022

30. The Relationship of Oral Health with Progression of Physical Frailty among Older Adults: A Longitudinal Study Composed of Two Cohorts of Older Adults from the United Kingdom and United States

Author

Rachel Kimble, A. Olia Papacosta, Lucy T. Lennon, Peter H. Whincup, Robert J. Weyant, John C. Mathers, S. Goya Wannamethee, and Sheena E. Ramsay

Subjects
Health Policy, General Medicine, Geriatrics and Gerontology, General Nursing
Abstract

To investigate the prospective associations between oral health and progression of physical frailty in older adults.Prospective analysis.Data are from the British Regional Heart Study (BRHS) comprising 2137 men aged 71 to 92 years from 24 British towns and the Health, Aging, and Body Composition (HABC) Study of 3075 men and women aged 70 to 79 years.Oral health markers included denture use, tooth count, periodontal disease, self-rated oral health, dry mouth, and perceived difficulty eating. Physical frailty progression after ∼8 years follow-up was determined based on 2 scoring tools: the Fried frailty phenotype (for physical frailty) and the Gill index (for severe frailty). Logistic regression models were conducted to examine the associations between oral health markers and progression to frailty and severe frailty, adjusted for sociodemographic, behavioral, and health-related factors.After full adjustment, progression to frailty was associated with dentition (per each additional tooth, odds ratio [OR] 0.97; 95% CI: 0.95-1.00),21 teeth with (OR 1.71; 95% CI: 1.01-2.88) or without denture use (OR 2.32; 95% CI 1.12-4.81), and symptoms of dry mouth (OR ≥1.8; 95% CI ≥ 1.06-3.10) in the BRHS cohort. In the HABC Study, progression to frailty was associated with dry mouth (OR 3.87; 95% CI 1.68-8.93) and ≥2 cumulative oral health problems (OR 2.54; 95% CI 1.27-5.10) and progression to severe frailty was associated with periodontal disease (pocket depth; OR 4.11; 95% CI 1.13-14.92) after full adjustment.These findings indicate that oral health problems, particularly tooth loss and dry mouth, in older adults are associated with progression to frailty in later life. Additional research is needed to determine if interventions aimed at maintaining (or improving) oral health can contribute to reducing the risk, and worsening, of physical frailty in older adults.

Published
2023

31. Inflammatory markers and incident heart failure in older men: the role of NT-proBNP

Author

S. Goya Wannamethee, Peter H. Whincup, Douglas G.J. McKechnie, Paul Welsh, Lucy T. Lennon, and A Olia Papacosta

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Clinical Biochemistry, Myocardial Infarction, Inflammation, 030204 cardiovascular system & hematology, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, cohort studies, cardiovascular disease, Risk Factors, Internal medicine, Natriuretic Peptide, Brain, Drug Discovery, medicine, Natriuretic peptide, Humans, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Aged, Heart Failure, Incidental Findings, Interleukin-6, business.industry, Biochemistry (medical), biomarkers, Middle Aged, medicine.disease, Peptide Fragments, United Kingdom, C-Reactive Protein, Quartile, B-type natriuretic peptide, Heart failure, Cardiology, medicine.symptom, business, Research Article, Cohort study
Abstract

Aim: To determine the relationship between baseline inflammation (CRP and IL-6) with natriuretic peptide (NP) activity (measured by NT-proBNP) and incident heart failure (HF) in older men. Methods & results: In the British Regional Heart Study, 3569 men without prevalent myocardial infarction or HF were followed for mean 16.3 years; 327 developed HF. Baseline CRP and IL-6 were significantly and positively associated with NT-proBNP. Those in the highest CRP and IL-6 quartiles had an elevated risk of HF after age and BMI adjustment (HR = 1.42 [1.01–1.98] and 1.71 [1.24–2.37], respectively), which markedly attenuated after NT-proBNP adjustment (HR = 1.15 [0.81–1.63] and 1.25 [0.89–1.75], respectively). Conclusion: NP activity is associated with pro-inflammatory biomarkers and may explain the link between inflammation and incident HF., Lay abstract Inflammation describes the body’s natural response to infections, injuries and toxins. Inflammation is a helpful response in the short term, but it is thought that long-lasting inflammation – for example, due to illnesses such as diabetes or obesity – may have harmful effects. Previous studies have found that people with higher levels of inflammatory molecules in the blood seem to be more likely to develop heart failure (HF) later on. The amount of fluid in the body is controlled, in part, by molecules in the blood known as ‘natriuretic peptides' (NPs). People with HF have much higher levels of NPs in their blood, and these are used to help diagnose HF. There are suggestions that inflammation and natriuretic peptides are linked to one another. Using a sample of men aged 60–79 years, who did not have HF, we compared blood markers of inflammation and NPs at a baseline examination. Men with higher blood inflammatory markers tended to have higher blood NP levels. We then followed these men up for an average of 16.3 years. Men with higher blood inflammatory markers at baseline were more likely to develop HF, as expected, even after accounting for differences in age and BMI. However, when we accounted for NP levels at baseline, the increased risk of HF with inflammation disappeared. This suggests that NP activity is important in the relationship between inflammation and the risk of HF. Future studies should account for this when examining the link. It is possible that NPs or, more likely, whatever is driving their release, may explain why people with inflammation are more likely to get HF.

Published
2021

32. Association between oral health markers and decline in muscle strength and physical performance in later life: longitudinal analyses of two prospective cohorts from the UK and the USA

Author

Rachel Kimble, Gillian McLellan, Lucy T Lennon, Anna Olia Papacosta, Robert J Weyant, Yvonne Kapila, John C Mathers, Sasiwarang Goya Wannamethee, Peter H Whincup, and Sheena E Ramsay

Subjects
Male, Psychiatry and Mental health, Tooth Loss, Health (social science), Humans, Female, Oral Health, Muscle Strength, Geriatrics and Gerontology, Physical Functional Performance, Family Practice, United Kingdom, Aged
Abstract

Poor oral health could be associated with changes in musculoskeletal health over time. This aim of this study was to investigate the longitudinal relationship between oral health and decline in physical function in later life.We did a prospective analysis of two cohorts of older adults (aged 70 years or older) including men from the British Regional Heart Study (BRHS; n=612), and men and women from the Health, Aging and Body Composition (Health ABC) Study (n=1572), followed up for about 8 years. Data were available for clinical or self-reported oral health measures, muscle (grip) strength, and physical performance (chair stand and gait speed). ANCOVA models were used to assess the association between oral health and follow-up physical function scores. Multivariate logistic regression models were used to examine the associations between oral health and decline in physical function over the follow-up period. In the BRHS, changes in oral health and physical function were also assessed. All models were adjusted for relevant sociodemographic, behavioural, and health-related factors.In the BRHS, complete tooth loss and difficulty eating were associated with weaker grip strength at follow-up, and periodontal status was associated with decline in gait speed. In the Health ABC Study, complete tooth loss, poor self-rated oral health, and the presence of one oral health problem were associated with slower gait speed at follow-up. In both studies, dry mouth was associated with declines in physical function. In the BRHS, deterioration of dentition (tooth loss) over the follow-up period was associated with decline in chair stand speed (adjusted odds ratio 2·34 [95% CI 1·20-4·46]), as was deterioration in difficulty eating (2·41 [1·04-5·60]).Oral health problems are associated with poorer physical function and greater decline in physical function in older adults, and could be an indicator of individuals at risk of reduced physical capacity and subsequent frailty and disability in later life.The Dunhill Medical Trust and the US National Institutes of Health-National Institute of Dental and Craniofacial Research.

Published
2022

34. Artificial intelligence enabled retinal vasculometry for prediction of circulatory mortality, myocardial infarction and stroke

Author

Alicja R Rudnicka, Roshan A Welikala, Sarah A Barman, Paul J Foster, Robert Luben, Shabina A Hayat, Kay-Tee Khaw, Peter H Whincup, David P Strachan, and Christopher G Owen

Abstract

AimsWe examine whether inclusion of Artificial Intelligence (AI)-enabled retinal vasculometry (RV) improves existing risk algorithms for incident stroke, myocardial infarction (MI) and circulatory mortality.MethodsAI-enabled retinal vessel image analysis processed images from 88,052 UK Biobank (UKB) participants (aged 40-69 years at image capture) and 7,411 EPIC-Norfolk participants (aged 48-92). Retinal arteriolar and venular width, tortuosity and area were extracted. Prediction models were developed in UKB using multivariable Cox proportional hazards regression for circulatory mortality, incident stroke and MI, and externally validated in EPIC-Norfolk. Model performance was assessed using optimism adjusted calibration, C- and R2 statistics. Performance of Framingham risk scores (FRS) for incident stroke and incident MI, with addition of RV to FRS, were compared with a simpler model based on RV, age, smoking status and medical history (antihypertensive/cholesterol lowering medication, diabetes, prevalent stroke/MI).ResultsUKB prognostic models were developed on 65,144 participants (mean age 56.8; median follow-up 7.7 years) and validated in 5,862 EPIC-Norfolk participants (67.6, 9.1 years respectively). Prediction models for circulatory mortality in men and women had optimism adjusted C- and R2 statistics between 0.75-0.77 and 0.33-0.44 respectively. For incident stroke and MI, addition of RV to FRS did not improve model performance in either cohort. However, the simpler RV model performed equally or better than FRS.ConclusionRV offers an alternative predictive biomarker to traditional risk-scores for vascular health, without the need for blood sampling or blood pressure measurement. Further work is needed to examine RV in population screening to triage individuals at high-risk. (250 words)HIGHLIGHTSWhat is already known on this topicPopulation screening for MI and stroke using risk prediction tools exist but have limited uptake; risk scores for circulator mortality do not exist.What this study addsRisk models developed in UK Biobank (validated in EPIC-Norfolk) using Artificial Intelligence (AI)-enabled retinal vasculometry (RV), age, history of cardiovascular disease, use of hypertensive medication and smoking yielded high predictive test performance for circulatory mortality.Risk scores for MI and stroke performed similarly to established risk scores.How this study might affect research, practice or policyAI-enabled RV extraction offers a non-invasive prognostic biomarker of vascular health that does not require blood sampling or blood pressure measurement, and potentially has greater community reach to identify individuals at medium-high risk requiring further clinical assessment.SYNOPSIS/PRECISRisk models developed in UK Biobank (validated in EPIC-Norfolk) using Artificial Intelligence enabled retinal vasculometry indices, age, history of cardiovascular disease, use of hypertensive medication and smoking yielded high predictive test performance for circulatory mortality. Risk scores for MI and stroke performed similarly to established risk scores.

Published
2022

35. Haematological variables and risk of future venous thromboembolism in the British Regional Heart Study on men. Combined D-dimer and APTT as a predictive test for thromboembolism?

Author

S. Goya Wannamethee, Olia Papacosta, Lucy Lennon, Peter H. Whincup, Ann Rumley, and Gordon D. O. Lowe

Subjects
Fibrin Fibrinogen Degradation Products, Male, Risk Factors, Humans, Partial Thromboplastin Time, Hematology, Obesity, Venous Thromboembolism, Biomarkers
Abstract

We examined the associations between haematological and inflammatory variables with future venous thromboembolism (VTE), in 3494 men aged 60-79 years, with no previous history of VTE or myocardial infarction, who were not receiving oral anticoagulants. After a mean follow-up period of 18 years, there were 149 confirmed cases of fatal or non-fatal VTE (deep vein thrombosis and/or pulmonary embolism). Among classical cardiovascular risk factors, only obesity and cigarette smoking were associated with VTE risk. After adjustment for age, obesity and smoking, VTE risk was associated with coagulation factor VIII, factor IX, von Willebrand factor (VWF), activated partial thromboplastin time (APTT), and fibrin D-dimer. Hazard ratios (95% CI) for top to bottom quarters (bottom to top for APTT), were respectively 2.17 (1.37, 3.44), 2.15 (1.30, 3.53), 2.02 (1.27, 3.22), 2.43 (1.47, 4.02) and 3.62 (2.18, 6.08). The 11% of men with both the shortest APTT and highest D-dimer combined had a 5.02 (2.37, 10.62) higher risk of VTE. VTE risk was not associated with fibrinogen, factor VII or activated protein C resistance; full blood count variables or with inflammatory markers, plasma viscosity, C-reactive protein or interleukin-6. The combination of D-dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores.

Published
2022

36. Associations between inflammation, coagulation, cardiac strain and injury, and subclinical vascular disease with frailty in older men: a cross-sectional study

Author

Douglas G. J. McKechnie, Meera Patel, A. Olia Papacosta, Lucy T. Lennon, Elizabeth A. Ellins, Julian P. J. Halcox, Sheena E. Ramsay, Peter H. Whincup, and S. Goya Wannamethee

Subjects
Aged, 80 and over, Inflammation, Male, Frailty, Interleukin-6, Pulse Wave Analysis, Carotid Intima-Media Thickness, Peptide Fragments, Cross-Sectional Studies, Troponin T, Cardiovascular Diseases, Risk Factors, Tissue Plasminogen Activator, Natriuretic Peptide, Brain, von Willebrand Factor, Humans, Vascular Diseases, Geriatrics and Gerontology, Biomarkers, Aged
Abstract

Background Inflammation, coagulation activation, endothelial dysfunction and subclinical vascular disease are cross-sectionally associated with frailty. Cardiac-specific biomarkers are less-well characterised. We assessed associations between these and frailty, in men with, and without, cardiovascular disease (CVD). Methods Cross-sectional analysis of 1096 men without, and 303 with, CVD, aged 71–92, from the British Regional Heart Study. Multinominal logistic regression was performed to examine the associations between frailty status (robust/pre-frail/frail) and, separately, C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), D-dimer, von Willebrand factor (vWF), high-sensitivity cardiac troponin-T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) (all natural log-transformed), and, in men without CVD, carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cfPWV), carotid distensibility coefficient (DC), and ankle-brachial pressure index (ABPI), adjusted for age, renal function, BMI, social class, smoking, polypharmacy, cognition, multimorbidity and systolic blood pressure. Explanatory variables with p Results In men without CVD, higher CRP, IL-6, vWF, tPA, hs-cTnT, NT-proBNP, cfPWV, and lower DC were significantly associated with frailty; mutually-adjusted, log IL-6 (OR for frailty = 2.02, 95%CI 1.38–2.95), log hs-cTnT (OR = 1.95, 95%CI 1.24–3.05) and DC (OR = 0.92, 95%CI 0.86–0.99) retained associations. In men with CVD, higher CRP, IL-6, and hs-cTnT, but not vWF, tPA, NT-proBNP or D-dimer, were significantly associated with frailty; mutually-adjusted, log hs-cTnT (OR 3.82, 95%CI 1.84–7.95) retained a significant association. Conclusions In older men, biomarkers of myocardial injury are associated with frailty. Inflammation is associated with frailty in men without CVD. Carotid artery stiffness is associated with frailty in men without CVD, independently of these biomarkers.

Published
2022

37. Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Author

Martina Müller-Nurasyid, Jerome I. Rotter, David M. Evans, John P. Kemp, Emelia J. Benjamin, Graciela E. Delgado, Vilmundur Gudnason, Ann Hammarstedt, Panos Deloukas, Aroon D. Hingorani, Riccardo E. Marioni, David Stacey, Jenny van Dongen, Eric Boerwinkle, Joachim Heinrich, Yongmei Liu, S. Goya Wannamethee, Delilah Zabaneh, Braxton D. Mitchell, Marie Standl, Jackie F. Price, Maria G. Stathopoulou, Yoav Ben-Shlomo, Joris Deelen, Eero Kajantie, Mohammadreza Abdollahi, Christie M. Ballantyne, Johan G. Eriksson, Ilkka Seppälä, Elnaz Naderi, Barbara J. Jefferis, Richard W Morris, Nicholas J. Timpson, George Dedoussis, Sirpa Jalkanen, Mika Kivimäki, Perminder S. Sachdev, Diana van Heemst, Melanie Waldenberger, Gaurav Singhal, Elisabeth Thiering, Olli T. Raitakari, Anders Hamsten, Zoltán Kutalik, L. Bain, Eco J. C. de Geus, Tarunveer S. Ahluwalia, Yuri Milaneschi, Hubert Scharnagl, Juan P. Casas, Georg Homuth, Claes Ohlsson, Abbas Dehghan, Nicola J. Armstrong, Behrooz Z. Alizadeh, Terho Lehtimäki, Steve E. Humphries, Naveed Sattar, Bram P. Prins, Peter Rossing, Sophie Visvikis-Siest, Joana A. Revez, Ilja M. Nolte, Stella Trompet, Harold Snieder, Marian Beekman, Diana Marek, Beate St Pourcain, Thorkild I. A. Sørensen, Silvia Naitza, Karen A. Mather, Uwe Völker, Eline Slagboom, Tina Shah, Magdalene C. Jawahar, Jens Baumert, Alexander Teumer, Dorret I. Boomsma, Marcus E. Kleber, Peter Vollenweider, Wolfgang Koenig, Brenda W.J.H. Penninx, Kenneth Rice, Ian J. Deary, Pedro Marques-Vidal, Donna K. Arnett, Eleonora Porcu, Jouke-Jan Hottenga, Maria Sabater-Lleal, Bruce M. Psaty, Matthias Nauck, Dan Mellström, Joel Eriksson, Bernhard T. Baune, Debbie A Lawlor, Catherine Toben, Peter H. Whincup, Toshiko Tanaka, Stavroula Kanoni, Katri Räikkönen, Gonneke Willemsen, Bengt Sennblad, Julian N. Trollor, Yalda Jamshidi, Sarah E. Harris, Jari Lahti, Joshua C. Bis, Peter Durda, Yen Pei C. Chang, Jorgen Engmann, Tom R. Gaunt, Stella Aslibekyan, Anbupalam Thalamuthu, Mary F. Feitosa, Angela Silveira, Tine Jess, Stela McLachlan, J. Wouter Jukema, Chen Lu, Simon P. Mooijaart, Tim D. Spector, Harald Grallert, Winfried März, Alexandros M. Petrelis, Manuel A. R. Ferreira, Meena Kumari, Stochastics, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Methodology, CHARGE Inflammation Working Group, Epidemiology, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Steno Diabetes Center, University of Copenhagen = Københavns Universitet (KU), University of Groningen [Groningen], Murdoch University, University of Alabama at Birmingham [ Birmingham] (UAB), QIMR Berghofer Medical Research Institute, University College of London [London] (UCL), Helmholtz-Zentrum München (HZM), Leiden University Medical Center (LUMC), University of Bristol [Bristol], University of Washington [Seattle], University of Maryland School of Medicine, University of Maryland System, Vrije Universiteit Amsterdam [Amsterdam] (VU), VU University Medical Center [Amsterdam], University of Heidelberg, Medical Faculty, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Sahlgrenska Academy at University of Gothenburg [Göteborg], National Institute for Health and Welfare [Helsinki], University of Helsinki, William Harvey Research Institute, Barts and the London Medical School, University of Queensland [Brisbane], School of Public Health [Boston], Boston University [Boston] (BU), MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council, University of Edinburgh, Amsterdam UMC, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche [Roma] (CNR), Karolinska Institutet [Stockholm], University of Tampere [Finland], Adelaide Medical School [Australia], University of Adelaide, Universität Greifswald - University of Greifswald, University of New South Wales [Sydney] (UNSW), Prince of Wales Hospital, Ludwig-Maximilians-Universität München (LMU), Baylor College of Medicine (BCM), Baylor University, Boston University School of Medicine (BUSM), VA Boston Healthcare System, Harokopio University of Athens, Max planck Institute for Biology of Ageing [Cologne], Larner College of Medicine [University of Vermont, Burlington], University of Vermont [Burlington], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, University of Turku, St George's, University of London, Statens Serum Institut [Copenhagen], Medical Faculty [Mannheim], Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Johannes Gutenberg - Universität Mainz (JGU), Vrije Universiteit Medical Centre (VUMC), British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Medical University Graz, Uppsala Universitet [Uppsala], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], University of Kentucky, Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University of Maryland [Baltimore], Queen Mary University of London (QMUL), University of Iceland [Reykjavik], Ludwig Maximilian University [Munich] (LMU), Melbourne School of Population and Global Health [Melbourne], University of Melbourne, Deutsches Herzzentrum München (DHM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Ulm (UUlm), University of Essex, Greifswald University Hospital, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), King‘s College London, University of Cambridge [UK] (CAM), Harbor UCLA Medical Center [Torrance, Ca.], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Human Genome Sequencing Center [Houston] (HGSC), Baylor University-Baylor University, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Clinicum, Department of Bacteriology and Immunology, Department of Public Health, Department of Psychology and Logopedics, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Doctoral Programme in Human Behaviour, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Subjects
AcademicSubjects/SCI01140, [SDV]Life Sciences [q-bio], Genome-wide association study, 030204 cardiovascular system & hematology, DISEASE, Pathogenesis, Cohort Studies, 0302 clinical medicine, cytokine, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Association Studies Article, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Genetics, 0303 health sciences, ARCHITECTURE, CHRONIC INFLAMMATION, 1184 Genetics, developmental biology, physiology, General Medicine, RECEPTOR IL-6R GENE, C-REACTIVE PROTEIN, hla-drb1 gene, 3. Good health, Medical genetics, Medical Genetics, chromosomes, medicine.medical_specialty, SUSCEPTIBILITY LOCI, European Continental Ancestry Group, Locus (genetics), Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, anti-inflammatory agents, White People, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Interleukin 6, Molecular Biology, Medicinsk genetik, 030304 developmental biology, PRODUCE IL-6, Interleukin-6, Chromosome, Receptors, Interleukin-6, RHEUMATOID-ARTHRITIS, Interleukin 1 Receptor Antagonist Protein, Gene Expression Regulation, Genetic Loci, CELLS, biology.protein, 1182 Biochemistry, cell and molecular biology, Human genome, 3111 Biomedicine, Genome-Wide Association Study, HLA-DRB1 Chains, Interleukin-1
Abstract

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Published
2021

38. Evaluating an Intervention to Increase Cereal Fiber Intake in Children: A Randomized Controlled Feasibility Trial

Author

Alicja R. Rudnicka, Michael Ussher, Rikard Landberg, Paul Welsh, Angela S Donin, Peter H. Whincup, Christopher G. Owen, Derek G Cook, Claire M Nightingale, Susan A. Jebb, Michael R. Perkin, Naveed Sattar, and Peymane Adab

Subjects
Dietary Fiber, Male, medicine.medical_specialty, type 2 diabetes risk, Medicine (miscellaneous), Type 2 diabetes, law.invention, AcademicSubjects/MED00060, Insulin resistance, Primary outcome, children, Group differences, Randomized controlled trial, dietary intervention, law, Internal medicine, Humans, Nutritional Epidemiology, Medicine, Child, Nutrition and Dietetics, business.industry, digestive, oral, and skin physiology, food and beverages, Cereal fiber, medicine.disease, Feasibility Studies, AcademicSubjects/SCI00960, feasibility trial, Female, Observational study, Edible Grain, business
Abstract

Background Observational studies have shown that higher cereal fiber intake is associated with reduced type 2 diabetes risk. However, it remains uncertain whether this association is causal. Objective This study evaluated the feasibility of an intervention to increase cereal fiber intake in children using breakfast cereals. Methods The study was a 2-arm parallel group randomized controlled trial in 9–10-y-old children, who received free supplies of high-fiber breakfast cereals (g3.5 g/portion) or low-fiber breakfast cereals (l1.0 g/portion) to eat daily for 1 mo with behavioral support to promote adherence. Children provided baseline and 1-mo fasting blood samples, physical measurements, and 24-h dietary recalls. The primary outcome was the group difference in change in plasma total alkylresorcinol (AR) concentration; secondary outcomes were group differences in nutrient intakes and adiposity indices. Analyses (complete case and multiple imputation) were conducted by regressing the final AR concentration on baseline AR in models adjusted for sex, ethnicity, age, and school (random effect). Results Two-hundred seventy-two children were randomly assigned (137 receiving a low-fiber and 135 a high-fiber diet) and 193 (71%) provided fasting blood samples at baseline and follow-up. Among randomized participants, median (IQR) of baseline AR was 43.1 (24.6–85.5) nmol/L and of cereal fiber intake was 4.5 (2.7–6.4) g; 87% of participants reported consuming the cereal on most or all days. Compared with changes in the low-fiber group, the high-fiber group had greater increases in AR (40.7 nmol/L; 95% CI: 21.7, 59.8 nmol/L, P l 0.0001) and in reported cereal fiber intake (2.9g/d; 95% CI: 2.0, 3.7 g; P l 0.0001). There were no appreciable differences in other secondary outcomes. Conclusions We have developed a simple and acceptable nutritional intervention that increases markers of daily cereal fiber intake in children. This intervention could be used to test whether increases in cereal fiber intake in children might reduce insulin resistance. This trial was registered at www.isrctn.com as ISRCTN33260236.

Published
2021

39. Joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality: a harmonised meta-analysis in more than 44 000 middle-aged and older individuals

Author

Morten W. Fagerland, Katrien Wijndaele, Maria Hagströmer, Ariel Chernofsky, Steven P. Hooker, Thomas Yates, Bjørge H. Hansen, Jakob Tarp, Nicole L. Spartano, Paddy C. Dempsey, Sigmund A. Anderssen, Ing-Mari Dohrn, Charlotte L. Edwardson, Martin G. Larson, Ramachandran S. Vasan, Peter H. Whincup, Barbara J. Jefferis, Virginia J. Howard, Eric J. Shiroma, I-Min Lee, Jostein Steene Johannessen, Ulf Ekelund, Keith M. Diaz, Ekelund, Ulf [0000-0003-2115-9267], Dohrn, Ing-Mari [0000-0003-2593-550X], Lee, I-Min [0000-0002-1083-6907], and Apollo - University of Cambridge Repository

Subjects
Time Factors, education, Physical activity, Physical Therapy, Sports Therapy and Rehabilitation, sedentary, death, Accelerometry, Cox proportional hazards regression, Humans, Medicine, Orthopedics and Sports Medicine, Prospective cohort study, Exercise, health care economics and organizations, Aged, Sedentary time, Mortality, Premature, business.industry, Original research, Mortality rate, General Medicine, Middle Aged, VDP::Medisinske Fag: 700::Idrettsmedisinske fag: 850, meta-analysis, accelerometer, Meta-analysis, Sedentary Behavior, business, All cause mortality, Demography
Abstract

Funder: National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East Midlands, Funder: National Institute on Aging, Funder: Stockholms Läns Landsting; FundRef: http://dx.doi.org/10.13039/501100004348, Funder: Norwegian Directorate for Public Health, Funder: Centrum for Idrottsforskning; FundRef: http://dx.doi.org/10.13039/501100005350, Funder: The Coca-Cola Company, Objectives: To examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality. Methods: We conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.0 to 14.5 years during which 3451 participants died (7.8% mortality rate). Associations between different combinations of moderate-to-vigorous intensity physical activity (MVPA) and sedentary time were analysed at study level using Cox proportional hazards regression analysis and summarised using random effects meta-analysis. Results: Across cohorts, the average time spent sedentary ranged from 8.5 hours/day to 10.5 hours/day and 8 min/day to 35 min/day for MVPA. Compared with the referent group (highest physical activity/lowest sedentary time), the risk of death increased with lower levels of MVPA and greater amounts of sedentary time. Among those in the highest third of MVPA, the risk of death was not statistically different from the referent for those in the middle (16%; 95% CI 0.87% to 1.54%) and highest (40%; 95% CI 0.87% to 2.26%) thirds of sedentary time. Those in the lowest third of MVPA had a greater risk of death in all combinations with sedentary time; 65% (95% CI 1.25% to 2.19%), 65% (95% CI 1.24% to 2.21%) and 263% (95% CI 1.93% to 3.57%), respectively. Conclusion: Higher sedentary time is associated with higher mortality in less active individuals when measured by accelerometry. About 30–40 min of MVPA per day attenuate the association between sedentary time and risk of death, which is lower than previous estimates from self-reported data.

Published
2020

40. Establishing reference intervals for triglyceride-containing lipoprotein subfraction metabolites measured using nuclear magnetic resonance spectroscopy in a UK population

Author

Jorgen Engmann, Tom R. Gaunt, Jackie F. Price, Amand F. Schmidt, Diana Kuh, Meena Kumari, Olia Papacosta, Nishi Chaturvedi, Alun D. Hughes, Juan P. Casas, Mika Kivimäki, Aroon D. Hingorani, Goya Wannamethee, Roshni Joshi, Steve E. Humphries, Tina Shah, Debbie A Lawlor, Peter H. Whincup, and Therese Tillin

Subjects
Male, Lipoproteins, Clinical Biochemistry, Population, Fraction (chemistry), 030204 cardiovascular system & hematology, epidemiology studies, lipids, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nuclear magnetic resonance, medicine, Humans, clinical studies, 030212 general & internal medicine, laboratory methods, Spectroscopy, education, Nuclear Magnetic Resonance, Biomolecular, Triglycerides, Research Articles, Aged, education.field_of_study, medicine.diagnostic_test, Triglyceride, Chemistry, Magnetic resonance imaging, General Medicine, Nuclear magnetic resonance spectroscopy, Middle Aged, Reference Standards, United Kingdom, Analytes, nuclear magnetic resonance, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Female, Particle size, Analytes Lipids, Lipoprotein
Abstract

Background Nuclear magnetic resonance (NMR) spectroscopy allows triglycerides to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these subfractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 triglyceride-containing lipoprotein subfraction metabolites. Methods Lipoprotein subfractions using the Nightingale NMR platform were measured in 9073 participants from four cohort studies contributing to the UCL-Edinburgh-Bristol consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for a disease-free population, by sex and age group (65 years), and in a subgroup population of participants with cardiovascular disease or type 2 diabetes. We also determined the distribution across body mass index and smoking status. Results The largest reference interval range was observed in the medium very-low density lipoprotein subclass (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among male and female participants, with the exception of triglyceride in high-density lipoprotein. Triglyceride subfraction concentrations in very-low density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and high-density lipoprotein subclasses increased with increasing age and increasing body mass index. Triglyceride subfraction concentrations were significantly higher in ever smokers compared to never smokers, among those with clinical chemistry measured total triglyceride greater than 1.7 mmol/L, and in those with cardiovascular disease, and type 2 diabetes as compared to disease-free subjects. Conclusion This is the first study to establish reference interval ranges for 14 triglyceride-containing lipoprotein subfractions in samples from the general population measured using the nuclear magnetic resonance platform. The utility of nuclear magnetic resonance lipid measures may lead to greater insights for the role of triglyceride in cardiovascular disease, emphasizing the importance of appropriate reference interval ranges for future clinical decision making.

Published
2020

41. Oral health problems and risk of incident disability in two studies of older adults in the United Kingdom and the United States

Author

Eftychia Kotronia, Heather Brown, Olia Papacosta, Lucy T. Lennon, Robert J. Weyant, Peter H. Whincup, Sasiwarang Goya Wannamethee, and Sheena E. Ramsay

Subjects
Oral Health, Xerostomia, United States, Disability Evaluation, Tooth Loss, Activities of Daily Living, Quality of Life, Humans, Disabled Persons, Prospective Studies, Geriatrics and Gerontology, Mobility Limitation, Periodontal Diseases, Aged
Abstract

Preventing oral health problems can be crucial for maintaining physical independence in older adults. We aimed to examine the associations of a range of oral health problems with incidence of disability in older adults.We used prospective data from the British Regional Health Study (BRHS) (N = 2147, 71-92 years), and the Health, Aging and Body Composition (HABC) study (USA) (N = 3075, 71-80 years). Oral health measures included tooth loss, periodontal disease, self-rated oral health, and self-reported dry mouth. Participants were followed for onset of disability over a follow-up period of 3 years. Onset of disability was assessed through new cases of mobility limitations, activities of daily living (ADL), and instrumental activities of daily living (IADL). Logistic regression was performed to calculate the odds of incident disability.In the BRHS, tooth loss was associated with greater odds of mobility limitations and ADL difficulties. Periodontal disease was associated with greater incidence of mobility limitations. Self-report of ≥3 dry mouth symptoms was associated with increased odds of incident mobility limitations and ADL difficulties (OR = 2.08, 95% CI 1.27-3.42; OR = 1.73, 95% CI 1.03-2.90). Fair/poor self-rated oral health was associated with greater incidence of IADL difficulties. In the HABC study, complete tooth loss was associated with greater incidence of mobility limitations (OR = 1.86, 95% CI 1.13-3.06), and fair/poor self-rated oral health was associated with increased odds of incident ADL difficulties (OR = 1.42, 95% CI 1.04-1.94).Oral health problems in older adults, particularly tooth loss, self-reported dry mouth and self-rated oral health were associated with greater incidence of disability. Poor oral health plays a potentially important role in the development of disability in older populations, which in turn is an essential part of quality of life and healthy aging.

Published
2022

42. Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts

Author

Amanda E Paluch, Shivangi Bajpai, David R Bassett, Mercedes R Carnethon, Ulf Ekelund, Kelly R Evenson, Deborah A Galuska, Barbara J Jefferis, William E Kraus, I-Min Lee, Charles E Matthews, John D Omura, Alpa V Patel, Carl F Pieper, Erika Rees-Punia, Dhayana Dallmeier, Jochen Klenk, Peter H Whincup, Erin E Dooley, Kelley Pettee Gabriel, Priya Palta, Lisa A Pompeii, Ariel Chernofsky, Martin G Larson, Ramachandran S Vasan, Nicole Spartano, Marcel Ballin, Peter Nordström, Anna Nordström, Sigmund A Anderssen, Bjørge H Hansen, Jennifer A Cochrane, Terence Dwyer, Jing Wang, Luigi Ferrucci, Fangyu Liu, Jennifer Schrack, Jacek Urbanek, Pedro F Saint-Maurice, Naofumi Yamamoto, Yutaka Yoshitake, Robert L Newton, Shengping Yang, Eric J Shiroma, and Janet E Fulton

Subjects
Adult, Adolescent, VDP::Medisinske Fag: 700::Helsefag: 800, Health Sciences, Public Health, Environmental and Occupational Health, Humans, Walking, Middle Aged, Hälsovetenskaper, Exercise, Aged, Proportional Hazards Models
Abstract

BACKGROUND: Although 10 000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged ≥18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47 471 adults, among whom there were 3013 deaths (10·1 per 1000 participant-years) over a median follow-up of 7·1 years ([IQR 4·3-9·9]; total sum of follow-up across studies was 297 837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10 901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 0·60 (95% CI 0·51-0·71) for quartile 2, 0·55 (0·49-0·62) for quartile 3, and 0·47 (0·39-0·57) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10 000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 0·67 [95% CI 0·56-0·83]) and a peak of 60 min (0·67 [0·50-0·90]), but not significant for time (min per day) spent walking at 40 steps per min or faster (1·12 [0·96-1·32]) and 100 steps per min or faster (0·86 [0·58-1·28]). INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. FUNDING: US Centers for Disease Control and Prevention.

Published
2022

44. Quantifying childhood fat mass: comparison of a novel height-and-weight-based prediction approach with DXA and bioelectrical impedance

Author

Peter H. Whincup, Alicja R. Rudnicka, Claire M Nightingale, Derek G Cook, Mohammed T Hudda, and Christopher G. Owen

Subjects
Male, Mean squared error, Epidemiology, Calibration (statistics), Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030209 endocrinology & metabolism, Brief Communication, Fat mass, 03 medical and health sciences, Absorptiometry, Photon, 0302 clinical medicine, Statistics, Electric Impedance, Humans, Body Weights and Measures, Longitudinal Studies, 030212 general & internal medicine, Reference standards, Mathematics, Nutrition and Dietetics, Body Weight, Body Height, Adipose Tissue, Calibration, Body Composition, Female, Bioelectrical impedance analysis, Weight based dosing
Abstract

Accurate assessment of childhood adiposity is important both for individuals and populations. We compared fat mass (FM) predictions from a novel prediction model based on height, weight and demographic factors (height–weight equation) with FM from bioelectrical impedance (BIA) and dual-energy X-ray absorptiometry (DXA), using the deuterium dilution method as a reference standard. FM data from all four methods were available for 174 ALSPAC Study participants, seen 2002–2003, aged 11–12-years. FM predictions from the three approaches were compared to the reference standard using; R2, calibration (slope and intercept) and root mean square error (RMSE). R2 values were high from ‘height–weight equation’ (90%) but lower than from DXA (95%) and BIA (91%). Whilst calibration intercepts from all three approaches were close to the ideal of 0, the calibration slope from the ‘height–weight equation’ (slope = 1.02) was closer to the ideal of 1 than DXA (slope = 0.88) and BIA (slope = 0.87) assessments. The ‘height–weight equation’ provided more accurate individual predictions with a smaller RMSE value (2.6 kg) than BIA (3.1 kg) or DXA (3.4 kg). Predictions from the ‘height–weight equation’ were at least as accurate as DXA and BIA and were based on simpler measurements and open-source equation, emphasising its potential for both individual and population-level FM assessments.

Published
2020

45. Associations of the systolic and diastolic components of orthostatic hypotension with markers of cardiovascular risk in older men: A cross-sectional analysis from The British Regional Heart Study

Author

SG Wannamethee, Sheena E Ramsay, Peter H. Whincup, Olia Papacosta, Stephen P. Juraschek, Artaza Gilani, and Lucy T. Lennon

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Cross-sectional study, Systole, Endocrinology, Diabetes and Metabolism, Diastole, Blood Pressure, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, Orthostatic vital signs, Hypotension, Orthostatic, 0302 clinical medicine, Von Willebrand factor, Risk Factors, Internal medicine, Internal Medicine, medicine, Natriuretic peptide, Humans, 030212 general & internal medicine, Endothelial dysfunction, Aged, Troponin T, biology, business.industry, Middle Aged, medicine.disease, Blood pressure, Cross-Sectional Studies, Cardiovascular Diseases, Heart Disease Risk Factors, biology.protein, Cardiology, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

The mechanisms underlying the association between orthostatic hypotension (OH) and cardiovascular disease are unclear. We investigated whether OH is associated with circulating cardiovascular risk markers. This was a cross-sectional analysis of 3857 older, community-dwelling men. “Consensus OH” was defined as a sitting-tostanding decrease in systolic blood pressure ≥20 mm Hg and/or diastolic blood pressure ≥10 mm Hg that occurred within three minutes of standing. Multiple generalized linear regression and logistic models were used to examine the association between cardiovascular risk markers and OH. Consensus OH was present in 20.2%, consisting of isolated systolic OH in 12.6%, isolated diastolic OH in 4.6%, and combined systolic and diastolic OH in 3.0%. Concentration of von Willebrand factor, a marker of endothelial dysfunction, was positively associated with isolated systolic OH (OR 1.35, 95% CI 1.05-1.73) and combined systolic and diastolic OH (OR 2.27, 95% CI 1.35-3.83); high circulating phosphate concentration, which may reflect vascular calcification, was associated with isolated diastolic OH (OR 1.53, 95% CI 1.04-2.25) and combined systolic and diastolic OH (OR 2.12, 95% CI 1.31-3.44), high-sensitivity troponin T, a marker of myocardial injury, was positively associated with isolated diastolic OH (OR 1.69, 95% CI 1.07-2.65) and N-terminal pro-brain natriuretic peptide, a marker of cardiac stress, was positively associated with combined systolic and diastolic OH (OR 2.14, 95% CI 1.14-4.03). In conclusion, OH is associated with some cardiovascular risk markers implicated in endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress. Clinicians should consider assessing cardiovascular risk in patients with OH.

Published
2020

46. Retinal Vascular Tortuosity and Diameter Associations with Adiposity and Components of Body Composition

Author

R.A. Welikala, Alicja R. Rudnicka, Paul J. Foster, Christopher G. Owen, David P. Strachan, Peter H. Whincup, Sarah Barman, and Robyn J. Tapp

Subjects
Adult, Male, medicine.medical_specialty, Waist, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030209 endocrinology & metabolism, alliedhealth, Tortuosity, Article, Retina, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, Mass index, 030212 general & internal medicine, Adiposity, Aged, Aged, 80 and over, Nutrition and Dietetics, business.industry, Retinal Vessels, Retinal, Retinal vascular tortuosity, Middle Aged, Circumference, medicine.disease, Obesity, Multilevel regression, chemistry, Microvessels, Cardiology, Body Composition, Female, business, biological
Abstract

The aim of this study was to assess whether adiposity or body composition relates to microvascular characteristics of the retina, indicative of cardiometabolic function. A fully automated QUARTZ software processed retinal images from 68,550 UK Biobank participants (aged 40-69 years). Differences in retinal vessel diameter and tortuosity with body composition measures from the Tanita analyzer were obtained by using multilevel regression analyses adjusted for age, sex, ethnicity, clinic, smoking, and Townsend deprivation index. Venular tortuosity and diameter increased by approximately 2% (P

Published
2020

47. Is child weight status correctly reported to parents? Cross-sectional analysis of National Child Measurement Programme data using ethnic-specific BMI adjustments

Author

Nicola Firman, Carol Dezateux, Kambiz Boomla, Mohammed T Hudda, Peter H. Whincup, and John Robson

Subjects
Male, Parents, obesity, South asia, Cross-sectional study, Service provision, Ethnic group, 030209 endocrinology & metabolism, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, children, London, Ethnicity, medicine, Humans, AcademicSubjects/MED00860, 030212 general & internal medicine, Child, Weight status, Body Weight, Public Health, Environmental and Occupational Health, General Medicine, medicine.disease, Obesity, Cross-Sectional Studies, Categorization, Child, Preschool, Female, Original Article, Psychology, Demography
Abstract

Background BMI underestimates and overestimates body fat in children from South Asian and Black ethnic groups, respectively. Methods We used cross-sectional NCMP data (2015–17) for 38 270 children in three inner-London local authorities: City & Hackney, Newham and Tower Hamlets (41% South Asian, 18.8% Black): 20 439 4–5 year-olds (48.9% girls) and 17 831 10–11 year-olds (49.1% girls). We estimated the proportion of parents who would have received different information about their child’s weight status, and the area-level prevalence of obesity—defined as ≥98th centile—had ethnic-specific BMI adjustments been employed in the English National Child Measurement Programme (NCMP). Results Had ethnic-specific adjustment been employed, 19.7% (3112/15 830) of parents of children from South Asian backgrounds would have been informed that their child was in a heavier weight category, and 19.1% (1381/7217) of parents of children from Black backgrounds would have been informed that their child was in a lighter weight category. Ethnic-specific adjustment increased obesity prevalence from 7.9% (95% CI: 7.6, 8.3) to 9.1% (8.7, 9.5) amongst 4–5 year-olds and from 17.5% (16.9, 18.1) to 18.8% (18.2, 19.4) amongst 10–11 year-olds. Conclusions Ethnic-specific adjustment in the NCMP would ensure equitable categorization of weight status, provide correct information to parents and support local service provision for families.

Published
2020

48. Retinal Vasculometry Associations With Glaucoma: Findings From the European Prospective Investigation of Cancer–Norfolk Eye Study

Author

Kay-Tee Khaw, Paul J. Foster, Anthony P Khawaja, Alicja R. Rudnicka, Christopher G. Owen, Robert Luben, Shabina Hayat, David P. Strachan, Sarah Barman, Peter H. Whincup, R.A. Welikala, David C Broadway, Michelle P.Y. Chan, Luben, Robert [0000-0002-5088-6343], Hayat, Shabina [0000-0001-9068-8723], and Apollo - University of Cambridge Repository

Subjects
Male, medicine.medical_specialty, Biometry, genetic structures, Glaucoma, Ocular hypertension, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ophthalmology, medicine, Humans, Prospective Studies, Intraocular Pressure, 030304 developmental biology, Aged, 0303 health sciences, business.industry, Cancer, Retinal Vessels, Retinal, Glaucoma suspect, medicine.disease, Confidence interval, eye diseases, Europe, Cross-Sectional Studies, chemistry, 030221 ophthalmology & optometry, Retinal imaging, Original Article, Female, sense organs, High intraocular pressure, business, biological, Glaucoma, Open-Angle, Tomography, Optical Coherence
Abstract

Purpose To examine retinal vasculometry associations with different glaucomas in older British people. Design Cross-sectional study. Methods A total of 8,623 European Prospective Investigation into Cancer-Norfolk Eye study participants were examined, who underwent retinal imaging, ocular biometry assessment, and clinical ascertainment of ocular hypertensive or glaucoma status (including glaucoma suspect [GS], high-tension open-angle glaucoma [HTG], and normal-tension glaucoma [NTG]). Automated measures of arteriolar and venular tortuosity, area, and width from retinal images were obtained. MainOutcomeMeasures: Associations between glaucoma and retinal vasculometry outcomes were analyzed using multilevel linear regression, adjusted for age, sex, height, axial length, intraocular and systemic blood pressure, and within-person clustering, to provide absolute differences in width and area, and percentage differences in vessel tortuosity. Presence or absence of within-person-between-eye differences in retinal vasculometry by diagnoses were examined. Results A total of 565,593 vessel segments from 5,947 participants (mean age 67.6 years, SD 7.6 years, 57% women) were included; numbers with HTG, NTG, and GS in at least 1 eye were 87, 82, and 439, respectively. Thinner arterioles (−3.2 μm; 95% confidence interval [CI] −4.4 μm, −1.9 μm) and venules (−2.7 μm; 95% CI −4.9 μm, −0.5 μm) were associated with HTG. Reduced venular area was associated with HTG (−0.2 mm2; 95% CI −0.3 mm2, −0.1 mm2) and NTG (−0.2 mm2; 95% CI −0.3 mm2, −0.0 mm2). Less tortuous retinal arterioles and venules were associated with all glaucomas, but only significantly for GS (−3.9%; 95% CI −7.7%, −0.1% and −4.8%; 95% CI −7.4%, −2.1%, respectively). There was no evidence of within-person-between-eye differences in retinal vasculometry associations by diagnoses. Conclusions Retinal vessel width associations with glaucoma and novel associations with vessel area and tortuosity, together with no evidence of within-person-between-eye differences in retinal vasculometry, suggest a vascular cause of glaucoma., Highlights • Retinal vessel measurements, including (as a first report) vessel tortuosity and area, were associated with high-tension glaucoma and other glaucoma-related outcomes. • Novel analyses showing that within-person-between-eye glaucoma diagnoses, intraocular pressure, and retinal vasculometry were uncorrelated provides further evidence that systemic microvascular changes may cause glaucoma.

Published
2020

49. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author

Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. 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Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. Patel, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Son Thai Pham, Simona Giampaoli, Dong Zhao, Indah Suci Widyahening, Merete Osler, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, Giota Touloumi, Janice Luisa Lukrafka, Adela Chirita-Emandi, Maryam Kavousi, Sanja Musić Milanović, Jean-Michel Gaspoz, Jalila El Ati, Sauli Herrala, Liang Xu, Pilar Guallar-Castillón, Bee Koon Poh, Luis Serra-Majem, Jonathan E. Shaw, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Yuki Fujita, Tiffany K. Gill, Nish Chaturvedi, Erkin M. Mirrakhimov, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Deepak Amarapurkar, Deepa Weerasekera, Diana A. 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Aroor Bhagyalaxmi , Sumit Bharadwaj , Santosh K Bhargava , Zulfiqar A Bhutta , Hongsheng Bi , Yufang Bi , Daniel Bia , Elysée Claude Bika Lele, Mukharram M Bikbov , Bihungum Bista , Dusko J Bjelica , Peter Bjerregaard , Espen Bjertness , Marius B Bjertness , Cecilia Björkelund , Katia V Bloch , Anneke Blokstra , Simona Bo , Martin Bobak , Lynne M Boddy , Bernhard O Boehm , Heiner Boeing , Jose G Boggia , Elena Bogova , Carlos P Boissonnet , Stig E Bojesen , Marialaura Bonaccio , Vanina Bongard , Alice Bonilla-Vargas , Matthias Bopp , Herman Borghs , Lien Braeckevelt , Lutgart Braeckman , Marjolijn Ce Bragt , Imperia Brajkovich , Francesco Branca , Juergen Breckenkamp , João Breda , Hermann Brenner , Lizzy M Brewster , Garry R Brian , Lacramioara Brinduse , Sinead Brophy , Graziella Bruno , H Bas Bueno-de-Mesquita , Anna Bugge , Marta Buoncristiano , Genc Burazeri , Con Burns , Antonio Cabrera de León , Joseph Cacciottolo , Hui Cai , Tilema Cama , Christine Cameron , José Camolas , Günay Can , Ana Paula C Cândido , Felicia Cañete , Mario V Capanzana , Nadežda Capková , Eduardo Capuano , Vincenzo Capuano , Marloes Cardol , Viviane C Cardoso , Axel C Carlsson , Esteban Carmuega , Joana Carvalho , José A Casajús , Felipe F Casanueva , Ertugrul Celikcan , Laura Censi , Marvin Cervantes-Loaiza , Juraci A Cesar , Snehalatha Chamukuttan , Angelique W Chan , Queenie Chan , Himanshu K Chaturvedi , Nish Chaturvedi , Norsyamlina Che Abdul Rahim , Miao Li Chee , Chien-Jen Chen , Fangfang Chen , Huashuai Chen , Shuohua Chen , Zhengming Chen , Ching-Yu Cheng , Bahman Cheraghian , Angela Chetrit , Ekaterina Chikova-Iscener , Arnaud Chiolero , Shu-Ti Chiou , María-Dolores Chirlaque , Belong Cho , Kaare Christensen , Diego G Christofaro , Jerzy Chudek , Renata Cifkova , Michelle Cilia , Eliza Cinteza , Frank Claessens , Janine Clarke , Els Clays , Emmanuel Cohen , Hans Concin , Susana C Confortin , Cyrus Cooper , Tara C Coppinger , Eva Corpeleijn , Simona Costanzo , Dominique Cottel , Chris Cowell , Cora L Craig , Amelia C Crampin , Ana B Crujeiras , Semánová Csilla , Alexandra M Cucu , Liufu Cui , Felipe V Cureau , Ewelina Czenczek-Lewandowska , Graziella D'Arrigo , Eleonora d'Orsi , Liliana Dacica , María Ángeles Dal Re Saavedra , Jean Dallongeville , Camilla T Damsgaard , Rachel Dankner , Thomas M Dantoft , Parasmani Dasgupta , Saeed Dastgiri , Luc Dauchet , Kairat Davletov , Guy De Backer , Dirk De Bacquer , Giovanni de Gaetano , Stefaan De Henauw , Paula Duarte de Oliveira , David De Ridder , Karin De Ridder , Susanne R de Rooij , Delphine De Smedt , Mohan Deepa , Alexander D Deev , Vincent Jr DeGennaro , Abbas Dehghan , Hélène Delisle , Francis Delpeuch , Stefaan Demarest , Elaine Dennison , Katarzyna Dereń , Valérie Deschamps , Meghnath Dhimal , Augusto F Di Castelnuovo , Juvenal Soares Dias-da-Costa , María Elena Díaz-Sánchez , Alejandro Diaz , Zivka Dika , Shirin Djalalinia , Visnja Djordjic , Ha Tp Do , Annette J Dobson , Maria Benedetta Donati , Chiara Donfrancesco , Silvana P Donoso , Angela Döring , Maria Dorobantu , Ahmad Reza Dorosty , Kouamelan Doua , Nico Dragano , Wojciech Drygas , Jia Li Duan , Charmaine A Duante , Priscilla Duboz , Rosemary B Duda , Vesselka Duleva , Virginija Dulskiene , Samuel C Dumith , Anar Dushpanova , Vilnis Dzerve , Elzbieta Dziankowska-Zaborszczyk , Ricky Eddie , Ebrahim Eftekhar , Eruke E Egbagbe , Robert Eggertsen , Sareh Eghtesad , Gabriele Eiben , Ulf Ekelund , Mohammad El-Khateeb , Jalila El Ati , Denise Eldemire-Shearer , Marie Eliasen , Paul Elliott , Reina Engle-Stone , Macia Enguerran , Rajiv T Erasmus , Raimund Erbel , Cihangir Erem , Louise Eriksen , Johan G Eriksson , Jorge Escobedo-de la Peña , Saeid Eslami , Ali Esmaeili , Alun Evans , David Faeh , Albina A Fakhretdinova , Caroline H Fall , Elnaz Faramarzi , Mojtaba Farjam , Victoria Farrugia Sant'Angelo , Farshad Farzadfar , Mohammad Reza Fattahi , Asher Fawwad , Francisco J Felix-Redondo , Trevor S Ferguson , Romulo A Fernandes , Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen Gironella , Aleksander Giwercman , Konstantinos Gkiouras , Justyna Godos , Sibel Gogen , Marcel Goldberg , Rebecca A Goldsmith , David Goltzman , Santiago F Gómez , Aleksandra Gomula , Bruna Goncalves Cordeiro da Silva , Helen Gonçalves , David A Gonzalez-Chica , Marcela Gonzalez-Gross , Margot González-Leon , Juan P González-Rivas , Clicerio González-Villalpando , María-Elena González-Villalpando , Angel R Gonzalez , Frederic Gottrand , Antonio Pedro Graça , Sidsel Graff-Iversen , Dušan Grafnetter , Aneta Grajda , Maria G Grammatikopoulou , Ronald D Gregor , Tomasz Grodzicki , Else Karin Grøholt , Anders Grøntved , Giuseppe Grosso , Gabriella Gruden , Dongfeng Gu , Emanuela Gualdi-Russo , Pilar Guallar-Castillón , Andrea Gualtieri , Elias F Gudmundsson , Vilmundur Gudnason , Ramiro Guerrero , Idris Guessous , Andre L Guimaraes , Martin C Gulliford , Johanna Gunnlaugsdottir , Marc J Gunter , Xiu-Hua Guo , Yin Guo , Prakash C Gupta , Rajeev Gupta , Oye Gureje , Beata Gurzkowska , Enrique Gutiérrez-González , Laura Gutierrez , Felix Gutzwiller , Seongjun Ha , Farzad Hadaegh , Charalambos A Hadjigeorgiou , Rosa Haghshenas , Hamid Hakimi , Jytte Halkjær , Ian R Hambleton , Behrooz Hamzeh , Dominique Hange , Abu Am Hanif , Sari Hantunen , Jie Hao , Rachakulla Hari Kumar , Seyed Mohammad Hashemi-Shahri , Maria Hassapidou , Jun Hata , Teresa Haugsgjerd , Jiang He , Yuan He , Yuna He , Regina Heidinger-Felso , Mirjam Heinen , Tatjana Hejgaard , Marleen Elisabeth Hendriks , Rafael Dos Santos Henrique , Ana Henriques , Leticia Hernandez Cadena , Sauli Herrala , Victor M Herrera , Isabelle Herter-Aeberli , Ramin Heshmat , Allan G Hill , Sai Yin Ho , Suzanne C Ho , Michael Hobbs , Michelle Holdsworth , Reza Homayounfar , Clara Homs , Wilma M Hopman , Andrea Rvr Horimoto , Claudia M Hormiga , Bernardo L Horta , Leila Houti , Christina Howitt , Thein Thein Htay , Aung Soe Htet , Maung Maung Than Htike , Yonghua Hu , José María Huerta , Ilpo Tapani Huhtaniemi , Laetitia Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , 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Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta 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Van Schoor , Irene Gm van Valkengoed , Dirk Vanderschueren , Diego Vanuzzo , Anette Varbo , Gregorio Varela-Moreiras , Patricia Varona-Pérez , Senthil K Vasan , Tomas Vega , Toomas Veidebaum , Gustavo Velasquez-Melendez , Biruta Velika , Giovanni Veronesi , Wm Monique Verschuren , Cesar G Victora , Giovanni Viegi , Lucie Viet , Salvador Villalpando , Paolo Vineis , Jesus Vioque , Jyrki K Virtanen , Marjolein Visser , Sophie Visvikis-Siest , Bharathi Viswanathan , Mihaela Vladulescu , Tiina Vlasoff , Dorja Vocanec , Peter Vollenweider , Henry Völzke , Ari Voutilainen , Sari Voutilainen , Martine Vrijheid , Tanja Gm Vrijkotte , Alisha N Wade , Aline Wagner , Thomas Waldhör , Janette Walton , Elvis Oa Wambiya , Wan Mohamad Wan Bebakar , Wan Nazaimoon Wan Mohamud , Rildo de Souza Wanderley Júnior , Ming-Dong Wang , Ningli Wang , Qian Wang , Xiangjun Wang , Ya Xing Wang , Ying-Wei Wang , S Goya Wannamethee , Nicholas Wareham , Adelheid Weber , Niels Wedderkopp , Deepa Weerasekera , Daniel Weghuber , Wenbin Wei , Aneta Weres , Bo Werner , Peter H Whincup , Kurt Widhalm , Indah S Widyahening , Andrzej Wiecek , Rainford J Wilks , Johann Willeit , Peter Willeit , Julianne Williams , Tom Wilsgaard , Bogdan Wojtyniak , Roy A Wong-McClure , Andrew Wong , Jyh Eiin Wong , Tien Yin Wong , Jean Woo , Mark Woodward , Frederick C Wu , Jianfeng Wu , Li Juan Wu , Shouling Wu , Haiquan Xu , Liang Xu , Nor Azwany Yaacob , Uruwan Yamborisut , Weili Yan , Ling Yang , Xiaoguang Yang , Yang Yang , Nazan Yardim , Mehdi Yaseri , Tabara Yasuharu , Xingwang Ye , Panayiotis K Yiallouros , Moein Yoosefi , Akihiro Yoshihara , Qi Sheng You , San-Lin You , Novie O Younger-Coleman , Safiah Md Yusof , Ahmad Faudzi Yusoff , Luciana Zaccagni , Vassilis Zafiropulos , Ahmad A Zainuddin , Seyed Rasoul Zakavi , Farhad Zamani , Sabina Zambon , Antonis Zampelas , Hana Zamrazilová , Maria Elisa Zapata , Abdul Hamid Zargar , Ko Ko Zaw , Tomasz Zdrojewski , Kristyna Zejglicova , Tajana Zeljkovic Vrkic , Yi Zeng 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Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santo, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, 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Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract

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., Wellcome Trust, Medical Research Council, peer-reviewed

Published
2021

50. Trajectories of physical activity from midlife to old age and associations with subsequent cardiovascular disease and all-cause mortality

Author

Peter H. Whincup, Lucy T. Lennon, Olia Papacosta, Sarah Ash, Barbara J. Jefferis, Daniel Aggio, S. Goya Wannamethee, and Efstathios Papachristou

Subjects
Adult, Male, Aging, Epidemiology, Health Behavior, Physical activity, physical activity, Disease, 030204 cardiovascular system & hematology, Lower risk, Secondary care, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, cardiovascular disease, Cause of Death, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Exercise, Original Research, Aged, Aged, 80 and over, business.industry, Confounding, Public Health, Environmental and Occupational Health, Middle Aged, CHD/coronorary heart, Ageing, ageing, life course epidemiology, Cardiovascular Diseases, Female, Sedentary Behavior, business, All cause mortality, Demography
Abstract

IntroductionIt is well established that physical activity (PA) protects against mortality and morbidity, but how long-term patterns of PA are associated with mortality and cardiovascular disease (CVD) remains unclear.Methods3231 men recruited to the British Regional Heart Study, a prospective cohort study, reported usual PA levels at baseline in 1978–1980 (aged 40–59 years) and at 12-year, 16-year and 20-year follow ups. Twenty-year trajectories of PA, spanning from 1978/1980 to 2000, were identified using group-based trajectory modelling. Men were subsequently followed up until 30 June 2016 for mortality through National Health Service central registers and for non-fatal CVD events through primary and secondary care records. Data analyses were conducted in 2019.ResultsThree PA trajectories were identified: low/decreasing (22.7%), light/stable (51.0%) and moderate/increasing (26.3%). Over a median follow-up of 16.4 years, there were 1735 deaths. Compared with the low/decreasing group, membership of the light/stable (HR 0.83, 95% CI 0.74 to 0.94) and moderate/increasing (HR 0.76, 95% CI 0.66 to 0.88) groups was associated with a lower risk of all-cause mortality. Similar associations were observed for CVD mortality, major coronary heart disease and all CVD events. Associations were only partially explained by a range of confounders. Sensitivity analyses suggested that survival benefits were largely driven by most recent/current PA.ConclusionsA dose-response relationship was observed, with higher levels of PA from midlife to old age associated with additional benefits. However, even fairly modest and sustained PA was protective and may be more achievable for the most inactive.

Published
2019

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