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Abstract Background Cardiometabolic diseases (CMD), including myocardial infarction, stroke, and type 2 diabetes, are leading causes of disability and mortality globally, particularly for people at an older age. The impact of adhering to the Life’s Simple 7 (LS7) on the number of years an individual will live without CMD in older adults remains less studied. Methods This study included a cohort of 2662 British men aged 60–79 years free of CMD at baseline from the British Regional Heart Study (BRHS). Each LS7 factor (BMI, blood pressure, blood glucose, total cholesterol, smoking, physical activity, and diet) was categorized as poor, intermediate, or ideal, and a composite LS7 adherence was determined by summing the number of LS7 ideal levels achieved. Flexible parametric Royston–Parmar proportional-hazards model was applied to estimate CMD-free life expectancy. Results Here we show that compared to men with the lowest LS7 adherence [with 18.42 years (95% CI: 16.93, 19.90) of CMD-free life at age 60], men having an ideal LS7 adherence are estimated to gain an additional 4.37 years (95% CI: 2.95, 5.79) of CMD-free life. The CMD-free life gain benefits are consistent across social class groups of manual and non-manual workers. Among LS7 factors, achieving an ideal physical activity provides the largest CMD-free survival benefit: 4.84 years (95% CI: 3.37, 6.32) of additional CMD-free life compared with the physically inactive group. Conclusions Our study quantifies and highlights the benefits of adhering to the LS7 ideal levels for living a longer life without CMD in older adults.

Abstract Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice. We proposed a simplified definition for assessing MetS risk in youths aged 6–17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89–0.92) and 0.79 (0.78–0.81) when using the IDF or NCEP definition as the gold standard, respectively. The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally.

Summary: Background: While people with type 2 diabetes (T2D) are more susceptible to infections, studies potentially underestimate the true burden of infection-related mortality since they rely on clinical coding systems primarily structured by body system, and by only focusing on underlying cause. This study examined cause-specific mortality in people with T2D compared to the general population during 2015–2019, focusing on infections. Methods: 509,403 people aged 41–90 years with T2D alive on 1/1/2015 in Clinical Practice Research Datalink were matched to 976,431 without diabetes on age, sex, and ethnicity. Recorded underlying cause of death was identified through national linked mortality data; infection-related deaths were counted across all ICD-10 (10th revision of the International Classification of Diseases) chapters, not just infection chapters A00-B99. All-cause and cause-specific hazard ratios (HR) for mortality during 2015–2019 compared people with T2D to people without diabetes and were estimated using Cox models adjusting for region. Additional analyses for sepsis related mortality considered the impact of including any mention of sepsis on the death certificate. Findings: 85,367/509,403 (16.8%) people with T2D died during 2015–2019 compared to 106,824/976,431 (10.9%) of people without diabetes of the same sex, age and ethnicity. All infections (11,128/85,367 = 13.0%) represented the third highest underlying cause of death among people with T2D after cardiovascular disease and cancer; a much higher contribution than counting only from specific infection chapters (1046/85,367 = 1.2%). The HR for people with T2D vs non-diabetes for all infection mortality (1.82, 95% CI 1.78–1.86) was higher than that estimated for all-cause (HR = 1.65, 95% CI 1.64–1.66). The estimated mortality rate associated with sepsis among people with T2D was highly dependent on whether any mention was included (2.2 per 1000 person-years) or only underlying cause (0.2 per 1000 person-years); but the HR for people with T2D vs non-diabetes was similar (any mention HR = 2.26, 95% CI 2.19–2.34 vs underlying cause only HR = 2.52, 95% CI 2.27–2.80). Interpretation: People with T2D die from infections at a higher rate than similar people without diabetes, and the overall burden is greater than previously reported. Routine statistics concentrating on underlying cause of death may somewhat under-estimate the importance of infections as causes of death among people with T2D. These findings emphasise the potential importance of awareness, earlier diagnosis and treatment of infections to prevent premature deaths. Funding: National Institute for Health and Care Research.

Abstract Background Waist-to-height ratio (WHtR) has been proposed as a simple and effective screening tool for assessing central obesity and cardiometabolic risk in both adult and pediatric populations. However, evidence suggests that the use of a uniform WHtR cut-off of 0.50 may not be universally optimal for pediatric populations globally. We aimed to determine the optimal cut-offs of WHtR in children and adolescents with increased cardiometabolic risk across different countries worldwide. Methods We used ten population-based cross-sectional data on 24,605 children and adolescents aged 6–18 years from Brazil, China, Greece, Iran, Italy, Korea, South Africa, Spain, the UK, and the USA for establishing optimal WHtR cut-offs. We performed an external independent test (9,619 children and adolescents aged 6–18 years who came from other six countries) to validate the optimal WHtR cut-offs based on the predicting performance for at least two or three cardiometabolic risk factors. Results Based on receiver operator characteristic curve analyses of various WHtR cut-offs to discriminate those with ≥ 2 cardiometabolic risk factors, the relatively optimal percentile cut-offs of WHtR in the normal weight subsample population in each country did not always coincide with a single fixed percentile, but varied from the 75th to 95th percentiles across the ten countries. However, these relatively optimal percentile values tended to cluster irrespective of sex, metabolic syndrome (MetS) criteria used, and WC measurement position. In general, using ≥ 2 cardiometabolic risk factors as the predictive outcome, the relatively optimal WHtR cut-off was around 0.50 in European and the US youths but was lower, around 0.46, in Asian, African, and South American youths. Secondary analyses that directly tested WHtR values ranging from 0.42 to 0.56 at 0.01 increments largely confirmed the results of the main analyses. In addition, the proposed cut-offs of 0.50 and 0.46 for two specific pediatric populations, respectively, showed a good performance in predicting ≥ 2 or ≥ 3 cardiometabolic risk factors in external independent test populations from six countries (Brazil, China, Germany, Italy, Korea, and the USA). Conclusions The proposed international WHtR cut-offs are easy and useful to identify central obesity and cardiometabolic risk in children and adolescents globally, thus allowing international comparison across populations.

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

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. Author summary Vessels at the back of the eye (the “retina”) can be imaged easily. This paper reports on the largest genetic study of retinal vessel shape and size characteristics so far undertaken, to the best of our knowledge. Our study is novel in using an automated artificial intelligence imaging approach to distinguish between arteries and veins, and in demonstrating more genetic associations with vessel characteristics than any previous study (119 genetic loci in all). We also show that the tortuosity of retinal arteries is the most strongly genetically determined vessel characteristic (replicated remarkable well in a separate second large dataset). In addition, using a particular type of genetic analysis (so called “Mendelian Randomization”) we show for the first time that the tortuosity of arteries in the retina is causally related to elevated diastolic blood pressure and not the other way around. This is important as it provides unique insights into the mechanism of elevated blood pressure and hypertension, providing pointers to novel therapeutic targets for future treatment.

Abstract Preventing deterioration of oral health in older age can be crucial for survival. We aimed to examine associations of oral health problems with all-cause, cardiovascular disease (CVD), and respiratory mortality in older people. We used cohort 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). Follow-up was 9 years (BRHS) and 15 years (HABC Study). Oral health comprised tooth loss, periodontal disease, dry mouth, and self-rated oral health. Cox regression was performed for all-cause mortality, competing risks for CVD mortality, and accelerated failure time models for respiratory mortality. In the BRHS, tooth loss was associated with all-cause mortality (hazard ratio (HR) = 1.59, 95% CI 1.09, 2.31). In the HABC Study, tooth loss, dry mouth, and having ≥ 3 oral problems were associated with all-cause mortality; periodontal disease was associated with increased CVD mortality (subdistribution hazard ratio (SHR) = 1.49, 95% CI 1.01, 2.20); tooth loss, and accumulation of oral problems were associated with high respiratory mortality (tooth loss, time ratio (TR) = 0.73, 95% CI 0.54, 0.98). Findings suggest that poor oral health is associated with mortality. Results highlight the importance of improving oral health to lengthen survival in older age.

Abstract Background Previous research has reported associations between features of the residential built environment and physical activity but these studies have mainly been cross-sectional, limiting inference. This paper examines whether changes in a range of residential built environment features are associated with changes in measures of physical activity in adults. It also explores whether observed effects are moderated by socio-economic status. Methods Data from the Examining Neighbourhood Activity in Built Living Environments in London (ENABLE London) study were used. A cohort of 1278 adults seeking to move into social, intermediate, and market-rent East Village accommodation was recruited in 2013–2015, and followed up after 2 years. Accelerometer-derived steps (primary outcome), and GIS-derived measures of residential walkability, park proximity and public transport accessibility were obtained both at baseline and follow-up. Daily steps at follow-up were regressed on daily steps at baseline, change in built environment exposures and confounding variables using multilevel linear regression to assess if changes in neighbourhood walkability, park proximity and public transport accessibility were associated with changes in daily steps. We also explored whether observed effects were moderated by housing tenure as a marker of socio-economic status. Results Between baseline and follow-up, participants experienced a 1.4 unit (95%CI 1.2,1.6) increase in neighbourhood walkability; a 270 m (95%CI 232,307) decrease in distance to their nearest park; and a 0.7 point (95% CI 0.6,0.9) increase in accessibility to public transport. A 1 s.d. increase in neighbourhood walkability was associated with an increase of 302 (95%CI 110,494) daily steps. A 1 s.d. increase in accessibility to public transport was not associated with any change in steps overall, but was associated with a decrease in daily steps amongst social housing seekers (− 295 steps (95%CI − 595, 3), and an increase in daily steps for market-rent housing seekers (410 95%CI -191, 1010) (P-value for effect modification = 0.03). Conclusion Targeted changes in the residential built environment may result in increases in physical activity levels. However, the effect of improved accessibility to public transport may not be equitable, showing greater benefit to the more advantaged.

Abstract Background Interventions to encourage active modes of travel (walking, cycling) may improve physical activity levels, but longitudinal evidence is limited and major change in the built environment / travel infrastructure may be needed. East Village (the former London 2012 Olympic Games Athletes Village) has been repurposed on active design principles with improved walkability, open space and public transport and restrictions on residential car parking. We examined the effect of moving to East Village on adult travel patterns. Methods One thousand two hundred seventy-eight adults (16+ years) seeking to move into social, intermediate, and market-rent East Village accommodation were recruited in 2013–2015, and followed up after 2 years. Individual objective measures of physical activity using accelerometry (ActiGraph GT3X+) and geographic location using GPS travel recorders (QStarz) were time-matched and a validated algorithm assigned four travel modes (walking, cycling, motorised vehicle, train). We examined change in time spent in different travel modes, using multilevel linear regresssion models adjusting for sex, age group, ethnicity, housing group (fixed effects) and household (random effect), comparing those who had moved to East Village at follow-up with those who did not. Results Of 877 adults (69%) followed-up, 578 (66%) provided valid accelerometry and GPS data for at least 1 day (≥540 min) at both time points; half had moved to East Village. Despite no overall effects on physical activity levels, sizeable improvements in walkability and access to public transport in East Village resulted in decreased daily vehicle travel (8.3 mins, 95%CI 2.5,14.0), particularly in the intermediate housing group (9.6 mins, 95%CI 2.2,16.9), and increased underground travel (3.9 mins, 95%CI 1.2,6.5), more so in the market-rent group (11.5 mins, 95%CI 4.4,18.6). However, there were no effects on time spent walking or cycling. Conclusion Designing walkable neighbourhoods near high quality public transport and restrictions on car usage, may offer a community-wide strategy shift to sustainable transport modes by increasing public transport use, and reducing motor vehicle travel.

Abstract Objective Kuwait has one of the highest obesity rates in the world. This study examined the associations between sedentary behaviour (objectively measured and self-reported), adiposity and systolic blood pressure in a sample of adolescents residing in Kuwait. Data was obtained from the Study of Health and Activity among adolescents in Kuwait (2012–2013). The sample included a total of 435 adolescents (201 boys). Outcomes were age- and sex specific body mass index Z-scores and systolic blood pressure. Exposures were total sedentary behaviour measured by accelerometry and time spent in some sedentary behaviours (television viewing, video games, computer use and total screen-time). We used multiple linear regression analyses, adjusted for age, governorate, maternal education and physical activity, to examine associations between sedentary behaviour and adiposity and systolic blood pressure. Results Only 2 statistically significant associations were found between sedentary behaviour and the study outcomes: body mass in boys was directly associated with higher sedentary time [β (95% CIs) 0.003 (0.00 to 0.06)]; body mass index was inversely associated with videogames in both sexes [girls: β (95% CIs) − 0.17 (− 0.48 to − 0.04); boys: − 0.24 (− 0.57 to − 0.12)]. In this sample of Kuwaiti adolescents, sedentary behaviour showed limited deleterious associations with adiposity and systolic blood pressure.

Abstract Background Few trials have compared estimates of change in physical activity (PA) levels using self-reported and objective PA measures when evaluating trial outcomes. The PACE-UP trial offered the opportunity to assess this, using the self-administered International Physical Activity Questionnaire (IPAQ) and waist-worn accelerometry. Methods The PACE-UP trial (N = 1023) compared usual care (n = 338) with two pedometer-based walking interventions, by post (n = 339) or with nurse support (n = 346). Participants wore an accelerometer at baseline and 12 months and completed IPAQ for the same 7-day periods. Main outcomes were weekly minutes, all in ≥10 min bouts as per UK PA guidelines of: i) accelerometer moderate-to-vigorous PA (Acc-MVPA) ii) IPAQ moderate+vigorous PA (IPAQ-MVPA) and iii) IPAQ walking (IPAQ-Walk). For each outcome, 12 month values were regressed on baseline to estimate change. Results Analyses were restricted to 655 (64%) participants who provided data on all outcomes at baseline and 12 months. Both intervention groups significantly increased their accelerometry MVPA minutes/week compared with control: postal group 42 (95% CI 22, 61), nurse group 43 (95% CI 24, 63). IPAQ-Walk minutes/week also increased: postal 57 (95% CI 2, 112), nurse 43 (95% CI -11, 97) but IPAQ-MVPA minutes/week showed non-significant decreases: postal -11 (95% CI -65, 42), nurse -34 (95% CI -87, 19). Conclusions Our results demonstrate the necessity of using a questionnaire focussing on the activities being altered, as with IPAQ-Walk questions. Even then, the change in PA was estimated with far less precision than with accelerometry. Accelerometry is preferred to self-report measurement, minimising bias and improving precision when assessing effects of a walking intervention. Trial registration: ISRCTN, ISRCTN98538934. Registered 2 March 2012.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Abstract Background Previous physical activity (PA) tracking studies have examined the stability of overall PA and/or PA types, but few have investigated how specific types of sport/exercise track over the life course. The aim of this study was to determine how specific sports/exercises in midlife track and predict future sport/exercise and PA in men transitioning to old age. Methods Seven thousand seven hundred thirty-five men (aged 40–59 years) recruited in 1978–80 were followed up after 12, 16 and 20 years. At each wave men self-reported participation in sport/exercise. Frequent sport/exercise participants (> 1/month) reported the types of sport/exercise they engaged in. Men also reported total PA, health status, lifestyle behaviours and socio-demographic characteristics. Stability of each sport/exercise was assessed using kappa statistics and intraclass correlation coefficients. Logistic regression estimated the odds of participating in sport/exercise and being active at 20-year follow up according to specific types of sport/exercise in midlife. Results Three thousand three hundred eighty-four men with complete data at all waves were included in analyses. Tracking of specific sports/exercises ranged from fair to substantial, with golf being the most common and most stable. Bowls was the most frequently adopted. Odds of participating in sport/exercise and being active in old age varied according to sport/exercise types in midlife. Golf and bowls in midlife were the strongest predictors of sport/exercise participation in old age. Golf, cricket and running/jogging in midlife were among the strongest predictors of being active in old age. Compared to participating in just one sport/exercise in midlife, sampling multiple sports/exercises was more strongly associated with sport/exercise participation and being active in old age. Conclusion The stability of sport/exercise participation from midlife to old age varies by type. Specific sports/exercises in midlife may be more likely to predict future PA than others. However, participating in a range of sports/exercises may be optimal for preserving PA into old age.

Abstract Background Research evaluating lifestyle interventions for prevention of cardiovascular disease (CVD) may not reach those most at risk. We compared the response rate to a randomised controlled trial (RCT) of a lifestyle intervention by CVD risk, ethnicity and level of deprivation. Methods Primary care patients with a QRisk2 score ≥ 20% were invited to participate in a RCT of an intensive lifestyle intervention versus usual care. This cross-sectional analysis compares anonymised data of responders and non-responders with multiple logistic regression, using adjusted odds ratios (AORs) for QRisk2 score, ethnicity, Index of Multiple Deprivation (IMD 2010) quintile, age and sex. Results From 60 general practices, 8902 patients were invited and 1489 responded. The mean age was 67.3 years and 21.0% were female. Of all patients invited, 69.9% were of white ethnic background, 13.9% ethnic minority backgrounds and 16.2% had no ethnicity data recorded in their medical records. Likelihood of response decreased as QRisk2 score increased (AOR 0.82 per 5 percentage points, 95% CI 0.77–0.88). Black African or Caribbean patients (AOR 0.67; 95% CI 0.45–0.98) and those with missing ethnicity data (AOR 0.55; 95% CI 0.46–0.66) were less likely to respond compared to participants of white ethnicity, but there was no difference in the response rates between south Asian and white ethnicity (AOR 1.08; 95% CI 0.84–1.38). Patients residing in the fourth (AOR 0.70; 95% CI 0.56–0.87) and fifth (AOR 0.52; 95% CI 0.40–0.68) most deprived IMD quintile were less likely to respond compared to the least deprived quintile. Conclusions Evaluations of interventions intended for those at high risk of CVD may fail to reach those at highest risk. Hard to reach patient groups may require different recruitment strategies to maximise participation in future trials. Improvements in primary care ethnicity data recording is required to aid understanding of how successfully study samples represent the target population. Trial registration ISRCTN, ISRCTN84864870. Registered 15 May 2012, https://doi.org/10.1186/ISRCTN84864870.

Abstract Background Increases in physical activity through active travel have the potential to have large beneficial effects on populations, through both better health outcomes and reduced motorized traffic. However accurately identifying travel mode in large datasets is problematic. Here we provide an open source tool to quantify time spent stationary and in four travel modes(walking, cycling, train, motorised vehicle) from accelerometer measured physical activity data, combined with GPS and GIS data. Methods The Examining Neighbourhood Activities in Built Living Environments in London study evaluates the effect of the built environment on health behaviours, including physical activity. Participants wore accelerometers and GPS receivers on the hip for 7 days. We time-matched accelerometer and GPS, and then extracted data from the commutes of 326 adult participants, using stated commute times and modes, which were manually checked to confirm stated travel mode. This yielded examples of five travel modes: walking, cycling, motorised vehicle, train and stationary. We used this example data to train a gradient boosted tree, a form of supervised machine learning algorithm, on each data point (131,537 points), rather than on journeys. Accuracy during training was assessed using five-fold cross-validation. We also manually identified the travel behaviour of both 21 participants from ENABLE London (402,749 points), and 10 participants from a separate study (STAMP-2, 210,936 points), who were not included in the training data. We compared our predictions against this manual identification to further test accuracy and test generalisability. Results Applying the algorithm, we correctly identified travel mode 97.3% of the time in cross-validation (mean sensitivity 96.3%, mean active travel sensitivity 94.6%). We showed 96.0% agreement between manual identification and prediction of 21 individuals’ travel modes (mean sensitivity 92.3%, mean active travel sensitivity 84.9%) and 96.5% agreement between the STAMP-2 study and predictions (mean sensitivity 85.5%, mean active travel sensitivity 78.9%). Conclusion We present a generalizable tool that identifies time spent stationary and time spent walking with very high precision, time spent in trains or vehicles with good precision, and time spent cycling with moderate precisionIn studies where both accelerometer and GPS data are available this tool complements analyses of physical activity, showing whether differences in PA may be explained by differences in travel mode. All code necessary to replicate, fit and predict to other datasets is provided to facilitate use by other researchers.

Abstract Background Maintenance of physical activity (PA) during later life is associated with optimal health; however, the long-term trajectories of PA into old age and their predictors have not been extensively researched using latent class methods. This study aimed to identify trajectories of self-reported PA and their predictors in men transitioning from midlife to old age. Methods 7735 men (aged 40–59 years) recruited in 1978–80 were followed up after 12, 16 and 20 years, reporting PA, health status, lifestyle behaviours and socio-demographic characteristics. Group-based trajectory modelling identified the trajectories of PA and associations with time-stable and time-varying covariates. We considered a range of sociodemographic and health and lifestyle factors as potential covariates. Results 4952 men (mean baseline age 49.1 ± 5.6 years) providing PA data at ≥3 time points were included in analyses. Three distinct 20-year trajectories were identified: low decreasing (24.6%, n = 1218), light stable (51.1%, n = 2530) and moderate increasing (24.3%, n = 1204). Being older, having a manual occupation, having never married or had children, residing in the midlands or North of England, suffering from a range of health conditions, being a smoker/ex-smoker and never consuming breakfast cereal or alcohol were independently associated with reduced odds of belonging to the moderate increasing trajectory group compared to the low decreasing group. Of the time-varying covariates considered, leaving employment was associated with a decrease in PA in the low decreasing group (β −0.306, p

BackgroundEvidence largely from animal studies suggests that conjugated linoleic acid (CLA) may have cardiovascular health benefits. However, few prospective studies have examined the association between CLA and cardiovascular disease. We have prospectively examined the association between serum CLA and incident coronary heart disease and heart failure (HF) in older men. Methods and ResultsProspective study of 3806 men, aged 60 to 79 years, without prevalent HF followed up for an average of 13 years, during which there were 295 incident HF cases. A high‐throughput serum nuclear magnetic resonance metabolomics platform was used to measure CLA concentration in serum, expressed as a percentage of total fatty acids (CLA%). CLA% was adversely associated with cholesterol and high‐density lipoprotein cholesterol but was inversely associated with C‐reactive protein and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; a marker of ventricular stress). No association was seen between CLA% and incident coronary heart disease. High CLA% was associated with significantly reduced risk of HF after adjustment for HF risk factors and C‐reactive protein (hazard ratio [95% confidence interval], 0.64 [0.43–0.96]; quartile 4 versus quartile 1). Elevated CLA% was associated with reduced HF risk only in those with higher dairy fat intake, a major dietary source of CLA (test for interaction P=0.03). The reduced risk of HF was partially explained by NT‐proBNP. High dairy fat intake was not associated with incident coronary heart disease but was associated with reduced risk of HF, largely because of the inverse effect of CLA. ConclusionsThe finding that high CLA% is associated with lower risk of incident HF in older men requires confirmation in larger studies.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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.