S. Bingham

General and Abdominal Adiposity and Risk of Death in Europe

BACKGROUND Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. METHODS We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. RESULTS During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P<0.001). CONCLUSIONS These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI in assessing the risk of death.

Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis

Aims/hypothesisWe examined the association between serum C-reactive protein (CRP) and incident diabetes in a prospective study, and added these data to a literature-based meta-analysis to explore potential sources of heterogeneity between studies.MethodsWe analysed a case–control study nested within the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, including 293 incident diabetes cases and 708 controls. We combined 16 published studies on CRP and incident diabetes in a random-effect meta-analysis.ResultsIn the EPIC-Norfolk cohort, serum CRP was associated with a higher risk of diabetes after adjusting for age, sex, BMI, family history of diabetes, smoking and physical activity (OR 1.49, comparing the extreme thirds of CRP distribution [95% CI 1.03–2.15], p = 0.03). However, the association was completely attenuated after further adjustment for WHR, serum γ-glutamyltransferase and serum adiponectin (OR 1.00; 95% CI 0.66–1.51, p = 1.0). In a meta-analysis of 16 published studies with 3,920 incident diabetes cases and 24,914 controls, the RR was 1.72 (95% CI 1.54–1.92), comparing the extreme thirds of CRP distribution, with substantial heterogeneity between studies (I2 = 52.8%, p = 0.007).Conclusions/interpretationInitial evidence of association between CRP and incident diabetes was confounded by central adiposity, markers of liver dysfunction and adiponectin in the primary analysis. Despite an overall positive association in the meta-analysis, considerable heterogeneity existed between studies. The degree of adjustment for central adiposity and baseline glycaemia explained some of this heterogeneity and suggests that CRP may not be an independent risk factor for type 2 diabetes.

Dietary assessment in Whitehall II: The influence of reporting bias on apparent socioeconomic variation in nutrient intakes

Objective: To assess socio-economic differences in nutrient intake, giving particular consideration to the influence of reporting bias.Design: Cross-sectional study. Three methods of data analysis (inclusion of all subjects, exclusion of low energy reporters, and regression-based energy adjustment) were evaluated against biomarkers of fatty acid and antioxidant intakes.Setting: London-based Civil Servants.Subjects: Age and employment grade stratified random sub-sample of 459 men and 406 women aged 39–61 y who completed 7 d diet diaries at Phase 3 follow-up (1991–93) of the Whitehall II Study.Dietary measures: Mean daily intakes by employment grade (6 levels) of dietary energy, total fat, saturated fatty acids, polyunsaturated fatty acids (PUFA), linoleic acid, carbohydrate excluding fibre, dietary fibre, protein, alcohol, vitamin C, vitamin E, carotenes, potassium and calcium. Biomarkers: serum cholesterol ester fatty acids (CEFA), total cholesterol, plasma α-tocopherol and β-carotene.Results: Low energy reporting (LER), defined as a reported energy intake below 1.2 times calculated basal metabolic rate, was strongly associated with employment grade (top grade: men 17.3%, women 19.3%, bottom grade: men 45.7%, women 49.2% trend P<0.0001 both sexes). This association is only to a small extent accounted for by the relative weight distribution across grades. The direct associations with grade—high status, high intakes—of total fat, saturated and polyunsaturated fatty acids seen in the results overall were greatly reduced or abolished when LER were excluded or when energy adjustment was used. Direct associations between grade and intakes of vitamin C and potassium in both sexes were evident regardless of data presentation method. Spearman correlations between biomarkers and reported intakes, for example CEFA and dietary linoleate (men 0.46, women 0.61), plasma β-carotene/cholesterol ratio and dietary carotenes (men 0.16, women 0.21) together with theoretical considerations indicate that energy adjustment may be the preferred method for reducing the influence of reporting bias.Conclusions: Low energy reporting is a major source of bias in dietary surveys and its prevalence shows a marked inverse association with socio-economic status. The energy adjustment method provides an approach which reduces this bias without exclusion of low energy reporters. Intakes of micronutrients including vitamin C, rather than fatty acids, showed associations with socio-economic status consistent with a dietary explanation for social inequalities in cardiovascular disease.Sponsorship: Ministry of Agriculture, Fisheries and Food and DH/MRC Nutrition Programme (SPG 9324537).

Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition

We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07–1.41, Ptrend=0.02). After calibration to allow for measurement error, we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1–72%, Ptrend=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.

Psychological distress, major depressive disorder, and risk of stroke

Background: Studies have suggested that mood status is associated with an increased risk of stroke, though mostly based on measures of depression defined by symptoms alone rather than diagnostic criteria representative of clinically important distress and impairment. We investigated this association based upon a large population-based prospective cohort study. Methods: Baseline assessment of major depressive disorder (MDD) and of mental health well-being (defined by the Mental Health Inventory, MHI-5) was completed by 20,627 stroke-free participants, aged 41 to 80 years, in the United Kingdom European Prospective Investigation into Cancer–Norfolk study. Results: During 8.5 years of follow-up, 595 incident (fatal and nonfatal) stroke endpoints were recorded. Neither past year nor lifetime MDD was associated with stroke. A one SD decrease in MHI-5 scale score (representing greater emotional distress) was associated with an 11% increased risk of stroke after adjustment for age, sex, cigarette smoking, systolic blood pressure, cholesterol, obesity, preexisting myocardial infarction, diabetes, social class, education, hypertension treatment, family history of stroke, and antidepressant medication use (hazard ratio 1.11, 95% CI 1.00 to 1.22). This association was consistent for men and for women, for fatal and nonfatal stroke, and conformed to a dose-response relationship. Conclusions: Findings from this large prospective cohort study suggest that increased psychological distress is associated with elevated stroke risk. Episodic major depressive disorder was not associated with incident stroke in this study.

Plasma Phyto-Oestrogens and Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition

We examined plasma concentrations of phyto-oestrogens in relation to risk for subsequent prostate cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition. Concentrations of isoflavones genistein, daidzein and equol, and that of lignans enterolactone and enterodiol, were measured in plasma samples for 950 prostate cancer cases and 1042 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of these phyto-oestrogens were estimated by conditional logistic regression. Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 (95% confidence interval (CI) 0.53–0.96, P trend=0.03). After adjustment for potential confounders this RR was 0.74 (95% CI 0.54–1.00, P trend=0.05). No statistically significant associations were observed for circulating concentrations of daidzein, equol, enterolactone or enterodiol in relation to overall risk for prostate cancer. There was no evidence of heterogeneity in these results by age at blood collection or country of recruitment, nor by cancer stage or grade. These results suggest that higher concentrations of circulating genistein may reduce the risk of prostate cancer but do not support an association with plasma lignans.

Does the association between self-rated health and mortality vary by social class?

Self-rated health (SRH) predicts future mortality. Individuals in different social classes with similar physical health status may have different reference levels and criteria against which they judge their health, therefore the SRH-mortality relationship may vary according to social class. We examine the relationship between SRH and mortality by occupational social class in a prospective study of 22,457 men and women aged 39-79 years, without prevalent disease, living in the general community in Norfolk, United Kingdom, recruited using general practice age-sex registers in 1993-1997 and followed up for an average of 10 years. As expected, SRH was related to subsequent mortality. The age and sex adjusted hazard ratio for mortality for those with poor compared to those with excellent SRH was 4.35 (95% confidence interval 3.38-5.59, P<0.001). The prevalence of poor or moderate SRH was higher in manual than in non-manual classes. However, SRH was similarly related to mortality in manual and non-manual classes: when non-manual classes are compared with manual classes for each category of SRH, the 95% confidence intervals for the mortality hazard ratios overlap. There was no evidence of an interaction between social class and SRH in either men or women. Thus in this population, SRH appears to predict mortality in a similar manner in non-manual and manual classes.

Refractive error, axial length and anterior chamber depth of the eye in British adults: the EPIC-Norfolk Eye Study

Purpose To describe the distribution, and demographic and socioeconomic correlates of refractive error and related ocular biometry in an older British population. Methods Refractive error was measured using an auto-refractor without cycloplegia. Pseudophakic individuals and those who had undergone refractive surgery were excluded from analysis. Axial length and anterior chamber depth were measured using partial coherence laser interferometry. Occupation category and highest educational achievement were recorded. Results Biometric data were available for 2519 people (1090 men, 1429 women; 93.2% of all participants) aged 48 to 88 years. Refractive data were available for both eyes in 2210 bilaterally phakic participants. Among phakic individuals, axial length of the eye was strongly inversely correlated with refractive error in both men and women (p<0.001). Axial length of the eye was strongly, independently related to height, weight and social class, but most strongly related to educational achievement. In contrast, anterior chamber depth varied with age and sex, but not with socioeconomic status. There was a significant inverse association between anterior chamber depth and refraction in women (p<0.001) but not in men (p=0.495). Conclusion Refractive error in this predominantly white older UK population was associated with axial biometry and sociodemographic characteristics. Educational status was the strongest determinant of axial length.

Cross-sectional association between total level and type of alcohol consumption and glycosylated haemoglobin level: the EPIC-Norfolk Study.

Objective: To investigate the association between total level and type of alcohol consumed and glycaemia.Design: Cross-sectional study.Setting: The EPIC-Norfolk Study, a population-based cohort study of diet and chronic disease.Subjects and methods: Non-diabetic men (n=2842) and women (n=3572), aged 40–78 y. Alcohol intake was assessed by self-reported questionnaire, and glycaemia measured by glycosylated haemoglobin (HbA1c).Results: Ten percent of men and 18% of women reported drinking no alcohol. Among drinkers, median alcohol intake was 8 units/week for men and 3 units/week for women. In analyses stratified by sex and adjusted for age, total energy intake, education, fruit and vegetable intake, smoking, family history of diabetes, physical activity, body mass index and waist:hip ratio, alcohol intake was inversely associated with HbA1c in men and women, although the association was stronger in women. A 1 unit/week increase in alcohol intake was associated with 0.0049% (s.e.=0.00223; P-value=0.028) and 0.017% (s.e.=0.00343; P-value <0.001) reduction in HbA1c in men and women respectively. In similar multivariate analyses, wine intake was inversely associated with HbA1c in men, and wine, spirits and beer intake were inversely associated with HbA1c in women. When also adjusted for total alcohol intake, only the association between wine intake and HbA1c in men remained significant.Conclusion: Alcohol intake was associated with lower HbA1c level, an association not explained by confounding. The distinction between type of alcohol consumed was particularly important in men.Sponsorship: NJW is an MRC Clinician Scientist Fellow.

Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective study

In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0.02), vitamin E (P = 0.04) and alcohol (P = 0.03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0.03, 0.04, and 0.03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.