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Background UK government spending on health has risen on average by 3.7% per year since 1948, outpacing economic growth over the period, with approximately a half of this expenditure used for hospitals. While physical activity interventions have been reported to reduce hospital stays, it is not clear if usual physical activity patterns may be associated with subsequent hospital use independently of other lifestyle factors. We examined the relationship between reported usual physical activity, change in usual physical activity and subsequent admissions to hospital and time spent in hospital for 11 228 men and 13 786 women aged 40–79 years in the general population over two sequential 10-year follow-up period taking into account demographic and lifestyle factors. Methods Participants from EPIC-Norfolk, a British prospective population-based cohort study were followed for 20 years (1999–2019) using record linkage to document hospital usage. Total physical activity was estimated by combining workplace and leisure time activity reported in a baseline lifestyle questionnaire and repeated with independent measures in a subset at a second time point approximately 12 years later. Results Compared to those reporting no physical activity, participants who were the most active had a lower likelihood of spending more than 20 days in hospital odds ratio (OR) 0.75 (95% confidence interval (CI) 0.67–0.83) over the next 10 years after multivariable adjustment for age, sex, smoking status, education, social class and body mass index. Similar results were seen for 10-year follow-up after the second time point OR 0.60 (95% CI 0.50–0.72). Participants reporting any activity had a mean of 0.42 fewer hospital days per year between 1999 and 2009 compared to inactive participants, an estimated potential saving to the National Health Service (NHS) of £247 per person per year, or approximately 7% of UK health expenditure. Participants who remained physically active or became active 12 years later had lower risk of subsequent hospital usage than those who remained inactive or became inactive, p-trend Conclusion Usual physical activity in this middle-aged and older population predicts lower future hospitalisations - time spent in hospital and number of admissions independently of behavioural and sociodemographic factors. Small feasible differences in usual physical activity in the general population may potentially have a substantial impact on hospital usage and costs.

Background Current policies do not support screening for future dementia among apparently healthy individuals. This is due to the lack of certainty of the clinical outcome and effective interventions. Numerous dementia risk models have been developed, currently, all within the research setting only. Studies have shown impairment in multiple cognitive domains several years before a clinical diagnosis of dementia. Methods We examined the utility of an extensive battery assessing a range of specific cognitive abilities as well as a composite global score, to predict dementia. Dementia outcomes were ascertained using electronic health record linkage in 8581 individuals (aged 48–92 years) taking part in the EPIC-Norfolk study. Participants were followed for 15 years (2004–2019). Risk of dementia was estimated using Cox proportional hazard models adjusting for sociodemographic, lifestyle and health variables, evaluating discriminative accuracy of the models by analysing receiver operating characteristic (ROC) curves. Results Poor cognition was predictive of incident dementia, even after adjustment for co-variates. Those with a poor performance score for global cognition (bottom 10%) were almost four times as likely to get a dementia diagnosis than those who performed well (HR=3.51 (95%CI 2.61, 4.71) P Discussion This study provides further insight on poor cognition predicting future dementia. This association was observed for global cognition and specific abilities, particularly for verbal episodic memory. Impairment occurs in multiple domains several years prior to a clinical diagnosis, and the more pervasive and greater the variability, the higher the risk of dementia. Deficits across multiple domains predict over and above individual test scores.

Background The ageing population and prevalence of long-term disorders with multimorbidity is a major health challenge worldwide. Patients with multimorbidity account for a disproportionately high share of healthcare workload and costs and experience reduced wellbeing and quality of life. The associations between comorbid conditions and mortality risk are well established; however, few prospective community-based studies have reported on prior risk factors for incident hospitalisations with multimorbidity. Our study examines the independent associations for a range demographic, lifestyle and physiological determinants and the likelihood of subsequent hospital incident multimorbidity using a prospective community-based cohort of middle-aged and older men and women resident in Norfolk, UK. We explore demographic, lifestyle and physiological exposures including age and sex, body mass index, cigarette smoking, alcohol intake, educational attainment, occupational social class, physical activity, plasma vitamin C, total cholesterol, systolic blood pressure and common prevalent diseases. Methods Incident hospital admissions with multimorbidity were examined in 25014 men and women aged 40–79 in EPIC-Norfolk, a British prospective population-based study initially recruited in 1993–1997 and followed-up until 2019. The determinants of incident multimorbidity, defined as Charlson Comorbidity Index ≥2, were examined in multivariable models for the 10-year period 1999–2009 and repeated with independent measurements in a second 10-year period 2009–2019. Results Between 1999–2009 18179 participants (73% of the population) had a hospital admission. Baseline 5-year and 10-year incident multimorbidity were observed in 11% and 21% of participants respectively. Age per 10-year increase OR 2.13 (95% CI 2.03–2.23) and male sex OR 1.28 (95% CI 1.17–1.39) predicted incident multimorbidity over 10 years. In the subset free of the most serious diseases at baseline, current smoking OR 1.71 (95% CI 1.53–1.91), BMI >30 kg/m² OR 1.37 (95% CI 1.24–1.51) and physical inactivity OR 1.09 (95% CI 1.00–1.18) were positively associated and plasma vitamin C (a biomarker of plant food intake) per SD increase OR 0.88 (95% CI 0.84–0.91) inversely associated with incident 10-year multimorbidity after multivariable adjustment for age, sex, social class, education, alcohol consumption, systolic blood pressure and cholesterol. Results were similar when re-examined for a further time period 2009–2019. Conclusion Age, male sex and potentially modifiable lifestyle behaviours including smoking, physical inactivity and low fruit and vegetable intake were associated with increased risk of future incident hospital admissions with multimorbidity.

Background Currently used models to predict cardiovascular event risk have limited value. It has been shown repetitively that the addition of single biomarkers has modest impact. Recently we observed that a model consisting of a larger array of plasma proteins performed very well in predicting the presence of vulnerable plaques in primary prevention patients. However, the validation of this protein panel in predicting cardiovascular outcomes remains to be established. Purpose This study investigated the ability of a 384 preselected protein biomarkers to predict acute myocardial infarction, using state-of-the-art machine learning techniques. Secondly, we compared the performance of this multi-protein risk model to traditional risk engines. Methods We selected 822 subjects from the EPIC-Norfolk prospective cohort study, of whom 411 suffered a myocardial infarction during follow-up (median 15 years) compared to 411 controls who remained event-free (median follow-up 20 years). The 384 proteins were measured using proximity extension assay technology. Machine learning algorithms (random forests) were used for the prediction of acute myocardial infarction (ICD code I21–22). Performance of the model was tested against and on top of traditional risk factors for cardiovascular disease (refit Framingham). All performance measurements were averaged over several stability selection routines. Results Prediction of myocardial infarction using a machine-learning model consisting of 50 plasma proteins resulted in a ROC AUC of 0.74±0.14, in comparison to 0.69±0.17 using traditional risk factors (refit Framingham. Combining the proteins and refit Framingham resulted in a ROC AUC of 0.74±0.15. Focussing on events occurring within 3 years after baseline blood withdrawal, the ROC AUC increased to 0.80±0.09 using 50 plasma proteins, as opposed to 0.67±0.22 using refit Framingham (figure). Combining the protein model with refit Framingham resulted in a ROC AUC of 0.82±0.11 for these events. Diagnostic performance events Conclusion High-throughput proteomics outperforms traditional risk factors in prediction of acute myocardial infarction. Prediction of myocardial infarction occurring within 3 years after inclusion showed highest performance. Availability of affordable proteomic approaches and developed machine learning pave the path for clinical implementation of these models in cardiovascular risk prediction. Acknowledgement/Funding This study was funded by an ERA-CVD grant (JTC2017) and EU Horizon 2020 grant (REPROGRAM, 667837)

Background Low social economic position is linked to higher rates of mortality and morbidity. Socioeconomic factors are reported to predict admission to hospital for many conditions. It is less clear if residential area deprivation index predicts hospital usage independently of individual social class and lifestyle factors. Methods We examined the relationship between residential Townsend’s Area Deprivation Index and subsequent admissions to hospital and time spent in hospital for 11,214 men and 13,763 women aged 40–79 years in the general population. Participants from the EPIC-Norfolk prospective population-based study were followed for nineteen years (1999–2018) using record linkage. Townsend’s Index from the small area measurements taken at the 1991 UK census was linked to individuals in the EPIC-Norfolk cohort using their postal code. Results Compared to those with residential Townsend Area Deprivation Index lower than the average for England and Wales, those with a higher than average deprivation index had a higher likelihood of spending more than twenty days in hospital multivariable adjusted odds ratio (OR) 1.18 (95% confidence interval (CI) 1.07–1.29) and having 7 or more admissions OR 1.11 (95% CI 1.02–1.22) after adjustment for age, sex, smoking status, education, social class, body mass index and prevalent diseases. Those with manual social class were at greater risk of hospitalisation compared to those with a non-manual social class when living in an area with higher deprivation index (p Interaction=0.025). Similarly, those with a lower education level living in a more deprived area had a higher risk of hospitalisation (p Interaction=0.020) when compared with those with a higher education level. Conclusion Residential area deprivation predicts future hospitalisations - time spent in hospital and number of admissions - independently of individual social class and education level and other behavioural factors. There are significant interactions such that residential area deprivation has greater impact in those with low education level or manual social class.

Cancer Research UK and Ludwig Cancer Research convened an inaugural international Cancer Prevention and Nutrition Conference in London on December 3–4, 2018. Much of the discussion focused on the need for systematic, interdisciplinary approaches to better understand the relationships of nutrition, exercise, obesity and metabolic dysfunction with cancer development. Scientists at the meeting underscored the importance of studying the temporal natural history of exposures that may cumulatively impact cancer risk later in life. A robust dialogue identified obesity as a major risk for cancer, and the food environment, especially high energy and low nutrient processed foods, as strong and prevalent risk factors for obesity. Further engagement highlighted challenges in the post-diagnostic setting, where similar opportunities to understand the complex interplay of nutrition, physical activity, and weight will inform better health outcomes. Going forward, holistic research approaches, encompassing insights from multiple disciplines and perspectives, will catalyze progress urgently needed to prevent cancer and improve public health.

BACKGROUND AND AIM: Obesity is a recognized risk factor for new-onset atrial fibrillation (AF). The association between body fat distribution, which is measured by body mass index (BMI) and waist-hip ratio (WHR), its changes, and new-onset AF is conflicting. METHODS AND RESULTS: Participants of the European Prospective Investigation into Cancer and Nutrition in Norfolk cohort study were included, with exclusion criteria of prevalent AF, rheumatic heart disease, and cancer. AF was confirmed by the International Classification of Diseases-10 hospital discharge code I48. Adjusted sex-specific Cox proportional hazards models were used to quantify the AF risk per 1 standard deviation increase and for quintiles of adiposity indices. A total of 10,885 men and 12,857 women were followed up for a median of 19 years, yielding 451,098 person-years. New-onset AF was diagnosed in 1408 (12.9%) men and 1102 (8.6%) women. Multivariable analyses showed that BMI predicted new-onset AF in all, while WHR predicted only in men. New-onset AF risk gradually increased across the range of adiposity indices: for men in the highest BMI quintile, HR: 1.59 (CI 1.32-1.91, p for trend

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol-metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study-specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol-metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer-specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta-analysed using fixed-effect and random-effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed-effect meta-analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low-grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression.

With increasing numbers of randomized controlled trials (RCTs) investigating potential health events of vitamin D supplementation, a better understanding is required of the risk factors for adverse events and for study withdrawals. This analysis aimed to identify baseline risk factors of reporting an adverse event in a multi-year randomized double-blinded placebo-controlled trial of vitamin D supplementation. The secondary aim was to investigate if adverse events were associated with study withdrawals. We analyzed data from the Vitamin D Assessment (ViDA) study: 5110 adults, aged 50–84 years, living in Auckland, New Zealand. Monthly doses of 100,000 IU vitamin D3 or placebo were mailed to participants homes, with a questionnaire to collect data on adverse events and adherence to the study capsule (initially monthly, then 4-monthly). Median follow-up was 3.3 years. Data were analysed using multivariable log-binomial regression and Cox-regression. During the follow-up period, 818 people reported adverse events and 412 withdrew or stopped returning questionnaires. Vitamin D was not associated with reporting of adverse events. Of sociodemographic factors, ethnicity was associated with reporting adverse events: compared to European participants, Maori and Pacific Islander people were more likely to report an adverse event. Non-smokers were more likely to report an adverse event, compared to smokers (adjusted hazard ratio (HR) = 1.80; 95%CI = 1.24, 2.62); as were those who had reported a history of depression (adjusted HR = 1.27; 95%CI = 1.01, 1.60) or a recent cough or cold (adjusted HR = 1.22; 95%CI = 1.03, 1.44) at baseline. Reporting of adverse events was not associated with withdrawals (adjusted HR = 1.12; 95%CI = 0.86, 1.46). These data did not identify any clear pattern in the factors associated with self-reported adverse events, which themselves did not increase risk of withdrawals.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from 375 incident pancreatic cancer cases and 375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval]=0.41-0.98; Ptrend =0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 =0.60; 95%CI=0.39-0.92; Ptrend =0.02) and docosapentaenoic acid (ORT3-T1 =0.52; 95%CI=0.32-0.85; Ptrend =0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 =3.00; 95%CI=1.13-7.99; Ptrend =0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 =0.37; 95%CI=0.17-0.81; Ptrend =0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 =3.40; 95%CI=1.39-8.34; Ptrend =0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking. This article is protected by copyright. All rights reserved.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

Udgivelsesdato: 2010-Nov-2 Background:Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.Methods:We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.Results:After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.Conclusion:Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.British Journal of Cancer advance online publication, 2 November 2010; doi:10.1038/sj.bjc.6605965 www.bjcancer.com.

Objective To quantify hospital use in a general population over 10 years follow-up and to examine related factors in a general population-based cohort. Design A prospective population-based study of men and women. Setting Norfolk, UK. Participants 11 228 men and 13 786 women aged 40–79 years in 1993–1997 followed between 1999 and 2009. Main outcomes measures Number of hospital admissions and total bed days for individuals over a 10-year follow-up period identified using record linkage; five categories for admissions (from zero to highest ≥7) and hospital bed days (from zero to highest ≥20 nights). Results Over a period of 10 years, 18 179 (72.7%) study participants had at least one admission to hospital, 13.8% with 7 or more admissions and 19.9% with 20 or more nights in hospital. In logistic regression models with outcome ≥7 admissions, low education level OR 1.14 (1.05 to 1.24), age OR per 10-year increase 1.75 (1.67 to 1.82), male sex OR 1.32 (1.22 to 1.42), manual social class 1.22 (1.13 to 1.32), current cigarette smoker OR 1.53 (1.37 to 1.71) and body mass index >30 kg/m² OR 1.41 (1.28 to 1.56) all independently predicted the outcome with p30 kg/m², estimated percentages of the cohort in the categories of admission numbers and hospital bed days in stratified age bands with twofold to threefold differences in future hospital use between those with high-risk and low-risk scores. Conclusions The future probability of cumulative hospital admissions and bed days appears independently related to a range of simple demographic and behavioural indicators. The strongest of these is increasing age with high body mass index and smoking having similar magnitudes for predicting risk of future hospital usage.

BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.

Aliment Pharmacol Ther 2011; 34: 1012–1019 Summary Background Studies of mortality in undetected coeliac disease compared with the general population give contradictory findings, suggesting it is either increased fourfold compared with the general population or not at all. Aim To establish all-cause and cause-specific mortality in undiagnosed coeliac disease, identified by anti-endomysial antibody (EMA) positivity, in the Cambridge GP Health Survey cohort. Method This cohort was recruited in 1990 from the general population aged 45–76 years. All deaths were ascertained from the Office for National Statistics. Mortality rates were calculated per 1000 person years and adjusted for age, gender, smoking and socioeconomic group using multivariate Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results There were 117 914 patient years of follow-up (median 16.8 years) from 7527 participants. Eighty-seven had undetected coeliac disease, their all-cause mortality rate was 9.4 per 1000 person years (95% CI 5.4–16.1) compared with 12.7 (95% CI 12.1–13.4) in EMA-negative participants. The adjusted all-cause mortality HR was 0.98 (95% CI 0.57–1.69). Death due to cancer and circulatory diseases was not increased, adjusted HR were 1.27 (95% CI 0.57–2.85) and 1.39 (95% CI 0.66–2.92) respectively. Conclusions We observed no excess overall mortality in people aged over 45 years with undetected coeliac disease compared with the general population, nor any increase in deaths related to circulatory disease or cancer. Our findings do not support screening the general population aged over 45 years, for coeliac disease for the purpose of improving life expectancy.

Aliment Pharmacol Ther 2011; 34: 649–655 Summary Background Aspirin has detrimental effects on the gastrointestinal tract mucosa and may play a role in the aetiology of inflammatory bowel disease. Aim To investigate if the regular use of aspirin is associated with the development of Crohn’s disease (CD) and ulcerative colitis (UC) using, for the first time, a prospective cohort study design. Methods A total of 135 780 men and women in Europe, aged 30–74 years, were recruited into the European Prospective Investigation into Cancer and Nutrition study. Participants completed questionnaires at baseline detailing their regular aspirin use and were then followed up to identify those who developed either incident CD or UC. Each case was matched with four controls and odds ratios (OR) were calculated, adjusting for cigarette smoking. Potential interactions between aspirin and smoking were assessed. Results A total of 35 participants developed CD and a further 84 were diagnosed with UC. Regular aspirin intake was positively associated with the risk of developing CD (OR = 6.14, 95% CI = 1.76–21.35). In those who took aspirin and smoked there was no detectable increased risk of CD (OR = 0.30, 95% CI = 0.03–3.08). No association was found between regular aspirin use and UC (OR = 1.29, 95% CI = 0.67–2.46). Conclusions A strong positive association between regular aspirin use and CD, but not UC, was observed. The data suggest that regular aspirin use should be measured in epidemiological work on CD. If such findings are consistent in other work then aspirin may affect the development of CD in a middle-aged to elderly population.

Udgivelsesdato: 2010-Jul-27 Objective:The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Subjects:This study included a representative sample of 24 310 randomly selected EPIC participants.Methods:Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000. Eating at restaurants was defined to include all eating and drinking occasions at restaurants, cafeterias, bars and fast food outlets. Eating at work included all eating and drinking occasions at the workplace. Associations between eating at restaurants or eating at work and BMI or annual weight changes were assessed using sex-specific linear mixed-effects models, controlling for potential confounders.Results:In southern Europe energy intake at restaurants was higher than intake at work, whereas in northern Europe eating at work appeared to contribute more to the mean daily intake than eating at restaurants. Cross-sectionally, eating at restaurants was found to be positively associated with BMI only among men (beta=+0.24, P=0.003). Essentially no association was found between BMI and eating at work among both genders. In a prospective analysis among men, eating at restaurants was found to be positively, albeit nonsignificantly, associated with weight gain (beta=+0.05, P=0.368). No association was detected between energy intake at restaurants and weight changes, controlling for total energy intake.Conclusion:Among men, eating at restaurants and similar establishments was associated with higher BMI and possibly weight gain.International Journal of Obesity advance online publication, 27 July 2010; doi:10.1038/ijo.2010.142.

Contains fulltext : 88547.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To examine the association between fruit and vegetable consumption and risk of different histological subtypes of lung cancer among participants of the European Prospective Investigation into Cancer and Nutrition study. METHODS: Multivariable Cox proportional hazard models were used to analyze the data. A calibration study in a subsample was used to reduce dietary measurement errors. RESULTS: During a mean follow-up of 8.7 years, 1,830 incident cases of lung cancer (574 adenocarcinoma, 286 small cell, 137 large cell, 363 squamous cell, 470 other histologies) were identified. In line with our previous conclusions, we found that after calibration a 100 g/day increase in fruit and vegetables consumption was associated with a reduced lung cancer risk (HR 0.94; 95% CI 0.89-0.99). This was also seen among current smokers (HR 0.93; 95% CI 0.90-0.97). Risks of squamous cell carcinomas in current smokers were reduced for an increase of 100 g/day of fruit and vegetables combined (HR 0.85; 95% CI 0.76-0.94), while no clear effects were seen for the other histological subtypes. CONCLUSION: We observed inverse associations between the consumption of vegetables and fruits and risk of lung cancer without a clear effect on specific histological subtypes of lung cancer. In current smokers, consumption of vegetables and fruits may reduce lung cancer risk, in particular the risk of squamous cell carcinomas. 01 maart 2010

BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.

Background We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association. Methods and results We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993–1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58 ± 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5 ± 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100 g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66–0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71–1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (N = 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66–1.01). Conclusions Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure., Highlights • Whether chocolate consumption increases or decreases the risk of heart failure remains controversial. • Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure. • Our meta-analysis found consistent findings across all studies that chocolate consumption does not increase the risk of incident heart failure. • Evidence suggests that chocolate consumption does not increase risk of heart failure at the general population level.

Background Objectively measured physical activity between older individuals and between populations has been poorly described. We aimed to describe and compare the variation in accelerometry data in older UK (EPIC-Norfolk) and American (NHANES) adults. Methods Physical activity was measured by uniaxial accelerometry in 4,052 UK (49–91 years) and 3459 US older adults (49–85 years). We summarized physical activity as volume (average counts/minute), its underlying intensity distribution, and as time spent 809 counts/minute is used 18.7 % of people reached the 30 min/day threshold. By comparison, 2.5 % and 9.5 % of American older adults accumulated activity at these levels, respectively. Conclusion As assessed by objectively measured physical activity, the majority of older adults in this UK study did not meet current activity guidelines. Older adults in the UK were more active overall, but also spent more time being sedentary than US adults. Electronic supplementary material The online version of this article (doi:10.1186/s12966-015-0316-z) contains supplementary material, which is available to authorized users.

Objective: To investigate the independent association between three different measures of socioeconomic status and plasma ascorbic acid level. Design: Cross-sectional population based study. Setting and participants: 20 292 men and women aged 39–79 y who participated in the EPIC-Norfolk study. Results: Individuals in manual social classes, who had no educational qualifications or those who lived in the most deprived areas had significantly lower levels of plasma ascorbic acid compared to those in nonmanual social classes, with at least O-level qualifications or who lived in less deprived areas. The magnitude of effect for each measure of socioeconomic status was greater in current smokers compared to current nonsmokers. Conclusion: Education and social class were stronger predictors of differences in ascorbic acid levels, an indicator of dietary health behaviour, than a deprivation index based on the Townsend score. This suggests that education could be particularly important in influencing large socioeconomic differentials in health related behaviours and potentially, health outcomes in the UK.

To examine the seroprevalence, correlates, and characteristics of undetected coeliac disease in a large adult population sample in Cambridge, UK.The Cambridge General Practice Health Study invited individuals from 12 general practices, aged 45-76 years, to attend for a health survey that included a bone density measurement, between 1990 and 1995. A total of 7550 participants' serum samples were tested for antiendomysial antibody (EMA). Seroprevalence of undetected coeliac disease was based on EMA positivity. Differences between EMA positive and negative participants of various physiological correlates and reported characteristics were estimated by multivariate logistic and linear regression and adjusted for age, sex, social class, and smoking behaviour.The seroprevalence of undetected coeliac disease in this general population sample aged 45-76 was 1.2% (95% confidence interval (CI) 0.9-1.4). EMA positive participants (n=87) were on average slightly lighter by 2.2 kg (p=0.08), were more likely to have reported their general health as being "good or excellent" (odds ratio (OR) 1.76 (95% CI 0.90-3.46)), and were less likely to report being a current smoker (OR for current versus never 0.36 (95% CI 0.14-0.90)) than EMA negative participants. EMA positivity was associated with an 8% reduction in mean serum cholesterol (0.5 mmol/l; p0.01) and reductions in mean haemoglobin (0.3 g/dl; p0.01), total protein (1.0 g/l; p0.05), and corrected serum calcium (0.02 mmol/l; p0.05). There was an increased risk of osteoporosis in EMA positive participants (OR 3.1 (95% CI 1.3-7.2)) and of mild anaemia (OR 4.6 (95% CI 2.5-8.2)) compared with EMA negative participants.Undetected coeliac disease is likely to affect approximately 1% of the population of England aged 45-76 years, a value similar to several other countries. Those affected report "better health" but they do have an increased risk of osteoporosis and mild anaemia. In contrast, they have a favourable cardiovascular risk profile that may afford protection from ischaemic heart disease and stroke.