Prospective associations between changes in physical activity and sedentary time and subsequent lean muscle mass in older English adults: the EPIC-Norfolk cohort study.

BACKGROUND: The longitudinal associations between physical behaviours and lean muscle mass indices need to be better understood to aid healthy ageing intervention development. METHODS: We assessed physical behaviours (total physical activity, moderate-to-vigorous physical activity (MVPA), light physical activity, total sedentary time and prolonged sedentary bout time) for 7 days using hip-worn accelerometers. We also assessed domain-specific physical behaviours (walking, cycling, gardening and housework time) with self-report questionnaires at baseline (2006-2011) and follow-up (2012-2016) in the European Prospective Investigation into Cancer (EPIC)-Norfolk study. We assessed body composition using dual-energy X-ray absorptiometry (DEXA) at follow-up in 1535 participants (≥ 60 years at baseline). From this, we derived appendicular lean muscle mass (ALM) indices (% relative ALM = (ALM/total body weight)*100), body mass index (BMI)-scaled ALM (ALM/BMI, kg/kg/m2) and height-scaled ALM (ALM/height2, kg/m2)). We evaluated the prospective associations of both baseline and change in physical behaviours with follow-up muscle mass indices using multivariable linear regression. RESULTS: Over 5.5 years (SD 14.8) follow-up, higher baseline accelerometer-measured physical activity and lower sedentary time were associated with higher subsequent relative ALM and BMI-scaled ALM, but not height-scaled ALM (e.g. 0.02% higher subsequent relative ALM per minute/day of baseline MVPA for men). Greater increases in physical activity and greater declines in sedentary time variables were associated with higher subsequent relative ALM and BMI-scaled ALM, but not height-scaled ALM (e.g. 0.001 kg/kg/m2 subsequent BMI-scaled ALM and 0.04% subsequent relative ALM per min/day/year increases in LPA over follow-up; 0.001 kg/kg/m2 subsequent BMI-scaled ALM and -0.03% subsequent relative ALM per min/day/year less of total sedentary time over follow-up). Greater increases in women's cycling and gardening over follow-up were associated with greater subsequent relative ALM (cycling 0.9% per hour/week/year; gardening 0.2% per hour/week/year) and BMI-scaled ALM (cycling 0.03 kg/kg/m2 per hour/week/year; gardening 0.004 kg/kg/m2 per hour/week/year). CONCLUSION: Physical behaviours across all intensities, and in women more specifically cycling and gardening, may help prevent age-related declines in muscle mass.

Plasma Metabolites Related to the Consumption of Different Types of Dairy Products and Their Association with New-Onset Type 2 Diabetes: Analyses in the Fenland and EPIC-Norfolk Studies, United Kingdom.

SCOPE: To identify metabolites associated with habitual dairy consumption and investigate their associations with type 2 diabetes (T2D) risk. METHODS AND RESULTS: Metabolomics assays were conducted in the Fenland (n = 10,281) and EPIC-Norfolk (n = 1,440) studies. Using 82 metabolites assessed in both studies, we developed metabolite scores to classify self-reported consumption of milk, yogurt, cheese, butter, and total dairy (Fenland Study-discovery set; n = 6035). Internal and external validity of the scores was evaluated (Fenland-validation set, n = 4246; EPIC-Norfolk, n = 1440). The study assessed associations between each metabolite score and T2D incidence in EPIC-Norfolk (n = 641 cases; 16,350 person-years). The scores classified low and high consumers for all dairy types with internal validity, and milk, butter, and total dairy with external validity. The scores were further associated with lower incident T2D: hazard ratios (95% confidence interval) per standard deviation: milk 0.71 (0.65, 0.77); butter 0.62 (0.57, 0.68); total dairy 0.66 (0.60, 0.72). These associations persisted after adjustment for known dairy-fat biomarkers. CONCLUSION: Metabolite scores identified habitual consumers of milk, butter, and total dairy products, and were associated with lower T2D risk. These findings hold promise for identifying objective indicators of the physiological response to dairy consumption.

Sex-specific lifetime risk of cardiovascular events: the European Prospective Investigation into Cancer-Norfolk prospective population cohort study.

AIMS: Better understanding of sex differences in cardiovascular disease (CVD) is essential in tailoring appropriate preventative strategies. Using a large population-based study with follow-up >25 years, we aimed to determine sex-specific lifetime risks of incident CVD and cardiovascular (CV) mortality amongst populations with and without prevalent CVD. METHODS AND RESULTS: Participants were drawn from the European Prospective Investigation into Cancer-Norfolk and followed up for a median of 26.2 years. Sex-specific lifetime risks were ascertained accounting for the competing risk of death. Models were adjusted for ethnicity and time-updated covariates: material deprivation, CV risk factors, lifestyle factors, comorbidities, and medication. A total of 23 859 participants [54.5% women; mean age (standard deviation) 59.2 (9.3) years at baseline] were included. Adjusted lifetime risks of incident CVD were higher in men than in women (69.1 vs. 57.7% at age 75): cause-specific hazard ratio (cHR) (99% confidence interval)-1.49 (1.41-1.57), while the risks of CV mortality at age 75 were 4.4% (men) and 3.1% (women): cHR-1.42 (1.31-1.54). Myocardial infarction was the predominant first presentation in men until the eighth decade. In women, the first CVD manifestations after their sixth decade were predominantly atrial fibrillation and stroke. The male-associated excess relative risks of incident CVD and CV mortality were halved in people with prevalent CVD. CONCLUSION: We characterized the sex-specific lifetime CV risks in a large cohort. Men had substantially higher risk of incident CVD and CV mortality than women, which was attenuated amongst people with prevalent CVD. Our findings provide an evidence base for sex-specific CV prevention.

In this population-based study, we aimed to understand the sex-specific lifetime trajectories of different heart and circulatory disorders and their relationship with death from heart disease. We included ∼24 000 participants in the analyses, who were followed up for >25 years. Men had a higher lifetime risk of heart and circulatory disorders compared with women. Heart attacks were the predominant first presentation in men until the eighth decade, while in women this was manifested as heart rhythm disorders and stroke after their sixth decade. The excess risk of death from heart disease observed in men with pre-existing heart disease was attenuated compared with those free of heart disease at baseline. In conclusion, men and women require tailored heart disease prevention efforts given the marked sex disparities in heart disease and death over the very long-term highlighted by our study.

Associations between change in physical activity and sedentary time and health-related quality of life in older english adults: the EPIC-Norfolk cohort study.

BACKGROUND: No previous studies have examined the associations between changes in objectively-measured physical behaviours with follow-up QoL in older adults. Based on cross-sectional evidence, it is biologically plausible that such associations exist. If so, this bolsters the case for the commissioning of activity interventions and for including QoL as an outcome in trials of such interventions. METHODS: We assessed physical behaviours (total physical activity, moderate-to-vigorous physical activity (MVPA), light physical activity, total sedentary time and prolonged sedentary bout time) for 7 days using hip-worn accelerometers at baseline (2006-2011) and follow-up (2012-2016) and health-related quality-of-life (QoL) using EQ-5D questionnaires at follow-up in 1433 participants (≥ 60 years) of the EPIC (European Prospective Investigation into Cancer)-Norfolk study. The EQ-5D summary score was used, with 0 as the worst to 1 as best perceived quality-of-life. We evaluated the prospective associations of baseline physical behaviours with follow-up QoL, and of changes in behaviours with follow-up QoL using multi-level regression. RESULTS: On average, MVPA decreased by 4.0 min/day/year (SD 8.3) for men and 4.0 min/day/year for women (SD 12.0) between baseline and follow-up. Total sedentary time increased by an average 5.5 min/day/yr (SD 16.0) for men and 6.4 min/day/yr (SD 15.0) for women between baseline and follow-up. Mean (SD) follow-up time was 5.8 (1.8) years. We found that higher baseline MVPA and lower sedentary time was associated with higher subsequent QoL (e.g. 1 h/day greater baseline MVPA was associated with 0.02 higher EQ-5D score, 95% CI 0.06, 0.36). More pronounced declines in activity were associated with worse Hr-QoL (0.005 (95% CI 0.003, 0.008) lower EQ-5D per min/day/yr decrease in MVPA). Increases in sedentary behaviours were also associated with poorer QoL (0.002 lower EQ-5D, 95% CI -0.003, -0.0007 per hour/day/yr increase in total sedentary time). CONCLUSIONS: Promotion of physical activity and limiting sedentary time among older adults may improve quality-of-life, and therefore this relationship ought to be included in future cost effectiveness analyses so that greater commissioning of activity interventions can be considered.

Calcaneal broadband ultrasound attenuation predicts physical capability: EPIC-Norfolk prospective population-based study.

BACKGROUND: Calcaneal ultrasound (broadband ultrasound attenuation - BUA), a marker of bone strength, may predict future physical capability and thus provide a strategy to identify individuals at risk of age-related deterioration of health. This study aims to determine if BUA can predict future physical capability among middle-aged and older adults. METHODS: Summary performance scores (SPS), an objective quantification of physical capability, were devised using participants' measures of standing balance, gait speed and timed chair rises. Associations between BUA and SPS, measured at least six years apart, were investigated using univariable and multivariate sex-specific linear and logistic regression, adjusting for confounders. RESULTS: 5893 participants were included. In men and women, for every five points lower BUA, there was a 0.2-point decrease in SPS. In women, BUA less than one standard deviation below the mean was associated with low physical capability (defined as SPS 3-6); fully adjusted odds ratio (OR) (95 % confidence interval (CI)) 1.35 (1.01-1.84). No association existed among men; OR (95 % CI) 0.84 (0.59-1.19). Significant risk factors for low physical capability in men with baseline low BUA were: older age [OR 5.77]; high BMI [OR 2.85]; lower social class [OR 1.59]; low physical activity [OR 1.64]. Risk factors among women were: older age [OR 5.54]; high BMI [OR 2.08]; lower education [OR 1.42], low physical activity [OR 1.27]; steroid use [OR 2.05]; and stroke [OR 2.74]. CONCLUSION: BUA may predict future physical capability in older adults. With further validation, BUA could stratify individuals at risk of deterioration in physical health.

Body Fat Percentage and the Long-term Risk of Fractures. The EPIC-Norfolk Prospective Population Cohort Study.

BACKGROUND: This cohort study aimed to determine the association between body fat percentage (BF%), incident fractures and calcaneal broadband ultrasound attenuation (BUA). METHODS: Participants were drawn from the EPIC-Norfolk Prospective Population Cohort Study (median follow-up = 16.4 years). Cox models analysed the relationship between BF% and incident fractures (all and hip). Linear and restricted cubic spline (RCS) regressions modelled the relationship between BF% and BUA. RESULTS: 14,129 participants (56.2 % women) were included. There were 1283 and 537 incident all and hip fractures respectively. The participants had a mean (standard deviation) age of 61.5 (9.0) years for women and 62.9 (9.0) years for men. Amongst men, BF% was not associated with incident all fractures. While BF% < 23 % (median) was not associated with hip fractures, BF% > 23 % was associated with increased risk of hip fractures by up to 50 % (hazard ratio (95 % confidence interval) = 1.49 (1.06-2.12)). In women, BF% < 39 % (median) was associated with up to 32 % higher risk of all fractures (1.32 (1.13-1.44)), while BF% > 35 % was not associated with this outcome. Higher BF% was associated with lower risk of incident hip fractures in women. Higher BF% was associated with higher BUA amongst women. Higher BF% up to ~23 % was associated with higher BUA amongst men. CONCLUSIONS: Higher BF% is associated with lower risk of fractures in women. While there was no association between BF% and all fractures in men, increasing BF% >23 % was associated with higher risk of hip fractures in men. This appears to be independent of estimated bone mineral density. Fracture prevention efforts need to consider wider physical, clinical, and environmental factors.

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

AIMS: We examine whether inclusion of artificial intelligence (AI)-enabled retinal vasculometry (RV) improves existing risk algorithms for incident stroke, myocardial infarction (MI) and circulatory mortality. METHODS: AI-enabled retinal vessel image analysis processed images from 88 052 UK Biobank (UKB) participants (aged 40-69 years at image capture) and 7411 European Prospective Investigation into Cancer (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-statistics 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). RESULTS: UKB prognostic models were developed on 65 144 participants (mean age 56.8; median follow-up 7.7 years) and validated in 5862 EPIC-Norfolk participants (67.6, 9.1 years, respectively). Prediction models for circulatory mortality in men and women had optimism adjusted C-statistics 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. CONCLUSION: RV 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.

Association between Legume Consumption and Risk of Hypertension in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Cohort.

Hypertension is a significant and preventable cardiovascular disease risk factor. Growing evidence suggests legumes have blood-pressure (BP) lowering properties. However, there is little population-based research on legume intake and hypertension risk in Western populations. The objective was to investigate the relationship between legume intake and blood pressure by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk cohort. Further, to identify any potential legume intake that confers benefits in relation to blood pressure. We included participants who completed both 7-day food diaries to assess legume intake and undertook a first (1993−1997) and second (1998−2000) health check from the EPIC-Norfolk prospective study. Legume consumption was categorized using percentile cut off values. We used multivariate logistic regression models to calculate the odds ratio of hypertension (defined as >140 mmHg systolic and/or >90 mmHg diastolic blood pressure) at the second health check, stratified by legume intake, adjusting for antihypertensive medication use and demographic, socioeconomic and lifestyle covariates. A total of 7522 participants were included with mean age (± SD) of 58.0 ± 8.9 years. The follow-up time was 3.7 years (range: 2.1−6.6 years). Mean legume consumption was 17.3 ± 16.3 g/day. Participants in the 97th percentile of legume intake had the lowest odds of subsequent hypertension (OR: 0.71; 95% CI: 0.52, 0.96). Legume consumption between 55−70 g/day was associated with reduced odds of hypertension (OR: 0.57; 95% CI: 0.37, 0.88); sex-specific values for men and women were 0.64 (0.38, 1.03) and 0.32 (0.12, 0.88), respectively. In this UK population, legume intake of 55−70 g/day was associated with a lower subsequent risk of hypertension. Given the low legume intake in the UK and Western countries, dietary guidance to increase intake above 55 g/day may lower the burden of hypertension and associated diseases.

Sex-specific associations between potassium intake, blood pressure, and cardiovascular outcomes: the EPIC-Norfolk study.

AIMS: A potassium replete diet is associated with lower blood pressure (BP) and lower risk of cardiovascular disease (CVD). Whether these associations differ between men and women and whether they depend on daily sodium intake is unknown. METHODS AND RESULTS: An analysis was performed in 11 267 men and 13 696 women from the EPIC-Norfolk cohort. Twenty-four hour excretion of sodium and potassium, reflecting intake, was estimated from sodium and potassium concentration in spot urine samples using the Kawasaki formula. Linear and Cox regression were used to explore the association between potassium intake, systolic BP (SBP), and CVD events (defined as hospitalization or death due to CVD). After adjustment for confounders, interaction by sex was found for the association between potassium intake and SBP (P < 0.001). In women, but not in men, the inverse slope between potassium intake and SBP was steeper in those within the highest tertile of sodium intake compared with those within the lowest tertile of sodium intake (P < 0.001 for interaction by sodium intake). Both in men and women, higher potassium intake was associated with a lower risk of CVD events, but the hazard ratio (HR) associated with higher potassium intake was lower in women than in men [highest vs. lowest potassium intake tertile: men: HR 0.93, 95% confidence interval (CI) 0.87-1.00; women: HR 0.89, 95% CI 0.83-0.95, P = 0.033 for interaction by sex]. CONCLUSION: The association between potassium intake, SBP, and CVD events is sex specific. The data suggest that women with a high sodium intake in particular benefit most from a higher potassium intake with regard to SBP.

Genetic control of serum 25(OH)D levels and its association with ethnicity.

BACKGROUND: Identified DNA variants associated with serum 25-hydroxyvitamin vitamin D (25[OH]D) concentration may provide mechanistic insights into the vitamin D metabolic pathway in individuals. Our aim was to further characterise participants and their serum 25(OH)D concentration at baseline using candidate single nucleotide polymorphism (SNP) genotyping. METHODS: 5110 participants, aged 50-84 years, were recruited from the community. Blood samples were collected at baseline to measure serum 25(OH)D by liquid chromatography mass spectrometry and the participants were genotyped for four markers close to or within genes in the vitamin D metabolic pathway known to be associated with differences in 25(OH)D. The markers and their associated genes were rs12785878 (DHCR7), rs10741657 (CYP2R1), rs4588 (DBP) and rs2228570 (VDR). RESULTS: All four markers had significantly different genotype distributions and minor allele frequencies between the four self-determined ethnicities (European/Other, Maori, Pacific, and South Asian). For example, the frequency in each ethnic group of the G allele for the marker rs12785878 was 0.26, 0.71, 0.89, and 0.78 respectively. Using multivariable regression in the full cohort, three out of four markers were significantly associated with baseline concentrations of 25(OH)D (mean differences: 2.9-10.9 nmol/L). Collectively, the four markers explained 8.4% of the variation in 25(OH)D concentrations. CONCLUSION: Significant ethnic variations exist in the distribution of alleles associated with serum 25(OH)D concentration, particularly rs12785878, in a multi-ethnic community sample from New Zealand.

Relationship of Sodium Intake With Granulocytes, Renal and Cardiovascular Outcomes in the Prospective EPIC-Norfolk Cohort.

Background Experimental studies show that high-sodium intake affects the innate immune system, among others with increased circulating granulocytes. Whether this relationship exists on a population level and whether this relates to disease outcomes is unclear. We aimed to test the hypotheses that (1) sodium intake is associated with granulocytes on a population level; (2) granulocytes are associated with the presence of hypertension and both cardiovascular and renal outcomes; and (3) the relation between high-sodium intake and these outcomes is mediated by granulocytes. Methods and Results We performed an analysis in 13 804 participants from the prospective EPIC (European Prospective Investigation into Cancer)-Norfolk cohort, with a mean age of 58 years and median follow-up of 19.3 years. Analyses were carried out using calculated estimated sodium intake and sodium-to-potassium ratios from spot urines at baseline. The main outcomes were hypertension at baseline, and composite cardiovascular (mortality or cardiovascular events) and renal (mortality or renal events) outcomes during follow-up. Sodium intake and urine sodium-to-potassium ratio were positively associated with circulating granulocyte concentrations after adjustment for confounders (ß=0.03; P=0.028 and ß=0.06; P<0.001, respectively). Granulocytes significantly mediated the associations of, respectively, sodium intake and urine sodium-to-potassium ratio with hypertension at baseline, and cardiovascular and renal outcomes. Conclusions Sodium intake is positively associated with circulating granulocyte concentrations, and higher granulocyte concentrations associate with worse long-term cardiovascular and renal outcomes. Given the recently established immune-modulating effects of sodium and the role of immune cells in both cardiovascular and renal disease, causality for this pathway may need consideration in further studies.

Evaluation of routinely collected records for dementia outcomes in UK: a prospective cohort study.

OBJECTIVES: To evaluate the characteristics of individuals recorded as having a dementia diagnosis in different routinely collected records and to examine the extent of overlap of dementia coding across data sources. Also, to present comparisons of secondary and primary care records providing value for researchers using routinely collected records for dementia outcome capture. STUDY DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: A cohort of 25 639 men and women in Norfolk, aged 40-79 years at recruitment (1993-1997) followed until 2018 linked to routinely collected to identify dementia cases. Data sources include mortality from death certification and National Health Service (NHS) hospital or secondary care records. Primary care records for a subset of the cohort were also reviewed. PRIMARY OUTCOME MEASURE: Diagnosis of dementia (any-cause). RESULTS: Over 2000 participants (n=2635 individuals) were found to have a dementia diagnosis recorded in one or more of the data sources examined. Limited concordance was observed across the secondary care data sources. We also observed discrepancies with primary care records for the subset and report on potential linkage-related selection bias. CONCLUSIONS: Use of different types of record linkage from varying parts of the UK's health system reveals differences in recorded dementia diagnosis, indicating that dementia can be identified to varying extents in different parts of the NHS system. However, there is considerable variation, and limited overlap in those identified. We present potential selection biases that might occur depending on whether cause of death, or primary and secondary care data sources are used. With the expansion of using routinely collected health data, researchers must be aware of these potential biases and inaccuracies, reporting carefully on the likely extent of limitations and challenges of the data sources they use.

Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study.

BACKGROUND: Higher medication anticholinergic burden is associated with increased risk of cardiovascular disease and cognitive decline. A mechanistic pathway has not been established. We aimed to determine whether inflammation may mediate these associations. METHODS: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). Anticholinergic burden score (ACB) was calculated at first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Fibrinogen and C-reactive protein (CRP) were measured during 1HC and tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for both health checks. Prospective associations were also examined between 1HC ACB and 2HC inflammatory markers. Models were adjusted for age, sex, lifestyle factors, comorbidities and medications. RESULTS: In total, 17 678 and 22 051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. Furthermore, 5101 participants with data on TNF-α and IL-6 were included in the prospective analyses. Cross-sectionally, compared to ACB = 0, ACB ≥ 4 was associated with higher fibrinogen, beta (95% confidence interval) = 0.134 g/L (0.070, 0.199), CRP 1.175 mg/L (0.715, 1.634), IL-6 0.593 pg/mL (0.254, 0.932) and TNF-α 0.137 pg/mL (0.033, 0.241). In addition, a point increase in ACB was associated with higher levels of all markers. Prospectively, compared to ACB = 0, ACB ≥ 4 was associated with higher IL-6(pg/mL) of 0.019 (-0.323, 0.361) and TNF-α (pg/mL) of 0.202% (0.81, 0.323). A unit increase in ACB was associated with a significantly higher TNF-α and IL-6. CONCLUSION: Higher ACB was associated with higher inflammatory markers. Inflammation may mediate the relationship between anticholinergic medications and adverse outcomes.

Physical activity intensity profiles associated with cardiometabolic risk in middle-aged to older men and women.

Accelerometers provide detailed data about physical activity (PA) across the full intensity spectrum. However, when examining associations with health, results are often aggregated to only a few summary measures [e.g. time spent "sedentary" or "moderate-to-vigorous" intensity PA]. Using multivariate pattern analysis, which can handle collinear exposure variables, we examined associations between the full PA intensity spectrum and cardiometabolic risk (CMR) in a population-based sample of middle-aged to older adults. Participants (n = 3660; mean ± SD age = 69 ± 8y and BMI = 26.7 ± 4.2 kg/m2; 55% female) from the EPIC-Norfolk study (UK) with valid accelerometry (ActiGraph-GT1M) data were included. We used multivariate pattern analysis with partial least squares regression to examine cross-sectional multivariate associations (r) across the full PA intensity spectrum [minutes/day at 0-5000 counts-per-minute (cpm); 5 s epoch] with a continuous CMR score (reflecting waist, blood pressure, lipid, and glucose metabolism). Models were sex-stratified and adjusted for potential confounders. There was a positive (detrimental) association between PA and CMR at 0-12 cpm (maximally-adjusted r = 0.08 (95%CI 0.06-0.10). PA was negatively (favourably) associated with CMR at all intensities above 13 cpm ranging between r = -0.09 (0.07-0.12) at 800-999 cpm and r = -0.14 (0.11-0.16) at 75-99 and 4000-4999 cpm. The strongest favourable associations were from 50 to 800 cpm (r = 0.10-0.12) in men, but from ≥2500 cpm (r = 0.18-0.20) in women; with higher proportions of model explained variance for women (R2 = 7.4% vs. 2.3%). Most of the PA intensity spectrum was beneficially associated with CMR in middle-aged to older adults, even at intensities lower than what has traditionally been considered "sedentary" or "light-intensity" activity. This supports encouragement of PA at almost any intensity in this age-group.

Face Validity of Observed Meal Patterns Reported with 7-Day Diet Diaries in a Large Population-Based Cohort Using Diurnal Variation in Concentration Biomarkers of Dietary Intake.

In a cross-sectional analysis of a population-based cohort (United Kingdom, N = 21,318, 1993-1998), we studied how associations between meal patterns and non-fasting triglyceride and glucose concentrations were influenced by the hour of day at which the blood sample was collected to ascertain face validity of reported meal patterns, as well as the influence of reporting bias (assessed using formula of energy expenditure) on this association. Meal size (i.e., reported energy content), mealtime and meal frequency were reported using pre-structured 7-day diet diaries. In ANCOVA, sex-specific means of biomarker concentrations were calculated by hour of blood sample collection for quartiles of reported energy intake at breakfast, lunch and dinner (meal size). Significant interactions were observed between breakfast size, sampling time and triglyceride concentrations and between lunch size, sampling time and triglyceride, as well as glucose concentrations. Those skipping breakfast had the lowest triglyceride concentrations in the morning and those skipping lunch had the lowest triglyceride and glucose concentrations in the afternoon, especially among acceptable energy reporters. Eating and drinking occasion frequency was weakly associated with glucose concentrations in women and positively associated with triglyceride concentrations in both sexes; stronger associations were observed for larger vs. smaller meals and among acceptable energy reporters. Associations between meal patterns and concentration biomarkers can be observed when accounting for diurnal variation and underreporting. These findings support the use of 7-day diet diaries for studying associations between meal patterns and health.

Self-reported physical functional health predicts future bone mineral density in EPIC-Norfolk cohort.

Using a large population sample from the UK, we found that self-reported physical functional health may be used to predict future bone mineral density especially in women. It may be a useful and inexpensive way to identify individuals before further decline in bone mineral density and the risk of fracture. PURPOSE: Self-reported physical functional health may predict bone mineral density (BMD) and thus provide a method to identify people at risk of low BMD. In this study, the association between the 36-item short-form questionnaire (SF-36) physical component summary (PCS) score and future BMD in participants aged 40-79 years enrolled in the European Prospective Investigation of Cancer-Norfolk study was investigated. METHODS: Associations between a participant's SF-36 PCS score, measured 18 months after baseline health check, and broadband ultrasound attenuation (BUA-a measure of BMD), measured 2-5 years after baseline, were examined using sex-specific linear and logistic regression analyses adjusting for age, BMI, medical co-morbidities, lifestyle and socioeconomic factors. RESULTS: Data from 10,203 participants, mean (standard deviation (SD)) age 61.5 (8.9) years (57.4% women), were analysed from 1993 to 2000. For every five points lower PCS score in men and women, there was approximately a 0.5 dB/MHz lower mean BUA. In women, a PCS score of less than one standard deviation (1SD) below the sex-specific mean was associated with having a low BUA (< 1SD below sex-specific mean) and very low BUA (< 2.5SD below the sex specific mean); odds ratio (OR) (95% confidence interval) 1.53 (1.24, 1.88) and 8.28 (2.67, 25.69), respectively. The relationship was lesser so in men; corresponding OR (95% CI) were 1.34 (0.91, 1.98) and 2.57 (0.72, 9.20), respectively. CONCLUSIONS: Self-reported physical functioning predicts BMD in an apparently healthy population, particularly in women. This could potentially provide an inexpensive, simple screening tool to identify individuals at risk of osteoporosis.

Risk factors for previously undiagnosed primary open-angle glaucoma: the EPIC-Norfolk Eye Study.

BACKGROUND AND AIM: Undiagnosed glaucoma is an invisible but important public health issue. At least half of glaucoma cases are estimated to be undiagnosed in western populations. The aim of this study is to examine risk factors for previously undiagnosed primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study within the European Prospective Investigation of Cancer-Norfolk Eye Study, a large-scale cohort study in the UK. PARTICIPANTS: 314 study participants with POAG in either eye. METHODS: Logistic regression was used to examine associations with previously undiagnosed POAG compared with previously diagnosed POAG. The factors examined included sociodemographic, ocular, physical and economic factors that could be barriers to eye care access. RESULTS: 217 participants had previously diagnosed POAG and 107 participants were newly diagnosed with POAG during the study. After adjusting for covariables, the factors significantly associated with previously undiagnosed POAG were: a lower pretreatment intraocular pressure (IOP) (OR 0.71/mm Hg, 95% CI 0.63 to 0.80, p<0.0001), and to have reported no problems with their eyesight (OR 0.03, 95% CI 0.01 to 0.10, p<0.0001). CONCLUSIONS: The risk factors for previously undiagnosed POAG identified in this study highlight the over-reliance on IOP level in glaucoma screening and the risk of missing glaucoma among lower IOP cases. It also suggests a role in improving glaucoma awareness in the community.

Long Term Prognostic Impact of Sex-specific Longitudinal Changes in Blood Pressure. The EPIC-Norfolk Prospective Population Cohort Study.

AIMS: We aimed to determine the sex differences in longitudinal systolic and diastolic blood pressure (SBP and DBP) trajectories in mid-life and delineate the associations between these and mortality (all-cause, cardiovascular, and non-cardiovascular) and incident cardiovascular disease (CVD) in old age. METHODS AND RESULTS: Participants were selected from the European Prospective Investigation into Cancer, Norfolk (EPIC-Norfolk) cohort study. Sex-specific trajectories were determined using group-based trajectory models using three clinic BP measurements acquired between 1993 and 2012 (mean exposure ∼12.9 years). Multivariable Cox regressions determined the associations between trajectories and incident outcomes over the follow-up (median follow-up 9.4 years). A total of 2897 men (M) and 3819 women (F) were included. At baseline, women were younger (F-55.5, M-57.1), had a worse cardiometabolic profile and were less likely to receive primary CVD prevention including antihypertensive treatment (F-36.0%, M-42.0%). Over the exposure period, women had lower SBP trajectories while men exhibited more pronounced SBP decreases over this period. Over the follow-up period, women had lower mortality (F-11.9%, M-20.5%) and CVD incidence (F-19.8%, M-29.6%). Compared to optimal SBP (≤120 mmHg) and DBP (≤70 mmHg) trajectories, hypertensive trajectories were associated with increased mortality and incident CVD in both men and women during follow-up at univariable level. These associations were nevertheless not maintained upon extensive confounder adjustment including antihypertensive therapies. CONCLUSION: We report sex disparities in CVD prevention which may relate to worse cardiometabolic profiles and less pronounced longitudinal SBP decreases in women. Effective anti-hypertensivetherapy may offset the adverse outcomes associated with prolonged exposure to high blood pressure.