Suzy Oakes

Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk)

Abstract Objective: To examine the value of glycated haemoglobin (HbA1c) concentration, a marker of blood glucose concentration, as a predictor of death from cardiovascular and all causes in men. Design: Prospective population study. Setting: Norfolk cohort of European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Subjects: 4662 men aged 45-79 years who had had glycated haemoglobin measured at the baseline survey in 1995-7 who were followed up to December 1999. Main outcome measures: Mortality from all causes, cardiovascular disease, ischaemic heart disease, and other causes. Results: Men with known diabetes had increased mortality from all causes, cardiovascular disease, and ischaemic disease (relative risks 2.2, 3.3, and 4.2, respectively, P <0.001 independent of age and other risk factors) compared with men without known diabetes. The increased risk of death among men with diabetes was largely explained by HbA1c concentration. HbA1c was continuously related to subsequent all cause, cardiovascular, and ischaemic heart disease mortality through the whole population distribution, with lowest rates in those with HbA1c concentrations below 5%. An increase of 1% in HbA1c was associated with a 28% (P<0.002) increase in risk of death independent of age, blood pressure, serum cholesterol, body mass index, and cigarette smoking habit; this effect remained (relative risk 1.46, P=0.05 adjusted for age and risk factors) after men with known diabetes, a HbA1c concentration ≥7%, or history of myocardial infarction or stroke were excluded. 18% of the population excess mortality risk associated with a HbA1c concentration ≥5% occurred in men with diabetes, but 82% occurred in men with concentrations of 5%-6.9% (the majority of the population). Conclusions: Glycated haemoglobin concentration seems to explain most of the excess mortality risk of diabetes in men and to be a continuous risk factor through the whole population distribution. Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA1c through behavioural means.

Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study

BACKGROUND Ascorbic acid (vitamin C) might be protective for several chronic diseases. However, findings from prospective studies that relate ascorbic acid to cardiovascular disease or cancer are not consistent. We aimed to assess the relation between plasma ascorbic acid and subsequent mortality due to all causes, cardiovascular disease, ischaemic heart disease, and cancer. METHODS We prospectively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes, and to cardiovascular disease, ischaemic heart disease, and cancer in 19 496 men and women aged 45-79 years. We recruited individuals by post using age-sex registers of general practices. Participants completed a health and lifestyle questionnaire and were examined at a clinic visit. They were followed-up for causes of death for about 4 years. Individuals were divided into sex-specific quintiles of plasma ascorbic acid. We used the Cox proportional hazard model to determine the effect of ascorbic acid and other risk factors on mortality. FINDINGS Plasma ascorbic acid concentration was inversely related to mortality from all-causes, and from cardiovascular disease, and ischaemic heart disease in men and women. Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile (p<0.0001). The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations. 20 micromol/L rise in plasma ascorbic acid concentration, equivalent to about 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality (p<0.0001), independent of age, systolic blood pressure, blood cholesterol, cigarette smoking habit, diabetes, and supplement use. Ascorbic acid was inversely related to cancer mortality in men but not women. INTERPRETATION Small increases in fruit and vegetable intake of about one serving daily has encouraging prospects for possible prevention of disease.

Television viewing and low participation in vigorous recreation are independently associated with obesity and markers of cardiovascular disease risk: EPIC-Norfolk population-based study

Objective: This study describes the associations between sedentary behaviour (television viewing) and participation in vigorous recreational activity with obesity and with biomarkers of cardiovascular disease (CVD) risk profile.Design: Cross-sectional analysis of the EPIC-Norfolk cohort study.Setting: The study is a population-based study of participants living in Norfolk, UK.Subjects: A total of 15 515 men and women aged between 45 and 74 y, recruited through General Practice lists, who completed the detailed physical activity questionnaire.Results: Following exclusion of those with self-reported myocardial infarction, stroke and diabetes, 14 189 participants remained for the analysis. Self-reported television viewing was positively and participation in vigorous activity negatively associated with markers of obesity, blood pressure and plasma lipids. In multiple regression analysis, adjusting for age, alcohol, smoking, treatment for hypertension, vigorous and total physical activity, these associations remained significant. For women who participated in more than 1 h/week of vigorous activity and who watched fewer than 2 h of television each day, the adjusted mean body mass index was 1.92 kg/m2 less than for women who reported participating in no vigorous activity and who watched more than 4 h of television each day (P<0.001). The equivalent figure for men was 1.44 kg/m2 (P<0.001). In a similar analysis, with blood pressure as the outcome, mean diastolic blood pressure difference between the extreme groups of vigorous activity and television viewing was 3.6 mmHg in men (P<0.001) and 2.7 mmHg (P=0.001) in women.Conclusions: These data suggest that time spent participating in vigorous recreational physical activity and television viewing, an indicator of a sedentary lifestyle, are associated with obesity and markers of CVD disease risk independent of total reported physical activity. Whether these observations represent the true underlying aetiological relations or are a manifestation of the different precision with which the subdimensions of activity are measured remains uncertain.

Nutritional methods in the European Prospective Investigation of Cancer in Norfolk.

OBJECTIVE To describe methods and dietary habits of a large population cohort. DESIGN Prospective assessment of diet using diet diaries and food-frequency questionnaires, and biomarkers of diet in 24-h urine collections and blood samples. SETTING Free living individuals aged 45 to 75 years living in Norfolk, UK. SUBJECTS Food and nutrient intake from a food-frequency questionnaire on 23 003 men and women, and from a 7-day diet diary from 2117 men and women. Nitrogen, sodium and potassium excretion was obtained from single 24-h urine samples from 300 individuals in the EPIC cohort. Plasma vitamin C was measured for 20 846 men and women. RESULTS The food-frequency questionnaire (FFQ) and the food diary were able to determine differences in foods and nutrients between the sexes and were reliable as judged by repeated administrations of each method. Plasma vitamin C was significantly higher in women than men. There were significant differences in mean intake of all nutrients measured by the two different methods in women but less so in men. The questionnaire overestimated dairy products and vegetables in both men and women when compared with intakes derived from the diary, but underestimated cereal and meat intake in men. There were some consistent trends with age in food and nutrient intakes assessed by both methods, particularly in men. Correlation coefficients between dietary intake assessed from the diary and excretion of nitrogen and potassium in a single 24-h urine sample ranged from 0.36 to 0.47. Those comparing urine excretion and intake assessed from the FFQ were 0.09 to 0.26. The correlations between plasma vitamin C and dietary intake from the first FFQ, 24-h recall or diary were 0.28, 0.35 and 0.40. CONCLUSIONS EPIC Norfolk is one of the largest epidemiological studies of nutrition in the UK and the largest on which plasma vitamin C has been obtained. Methods for obtaining food and nutrient intake are described in detail. The results shown here for food and nutrient intakes can be compared with results from other population studies utilising different methods of assessing dietary intake. The utility of different methods used in different settings within the main EPIC cohort is described. The FFQ is to be used particularly in pooled analyses of risk from diet in relation to cancer incidence within the larger European EPIC study, where measurement error is more likely to be overcome by large dietary heterogeneity on an international basis. Findings in the UK, where dietary variation between individuals is smaller and hence the need to use a more accurate individual method greater, will be derived from the 7-day diary information on a nested case-control basis. 24-h recalls can be used in the event that diary information should not be forthcoming from some eventual cases. Combinations of results utilising all dietary methods and biomarkers may also be possible.

Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus: EPIC-Norfolk prospective population study

BACKGROUND A quarter of fractures needing admission happen in men, but few data are available that show the value of bone measures for prediction of fracture risk in men. We aimed to assess quantitative ultrasound of the calcaneum and fracture incidence in a prospective observational population study. METHODS Calcaneum broadband ultrasound attenuation (BUA) was measured in men and women in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) between 1997 and 2000. Incident fractures were ascertained by hospital record linkage. FINDINGS In 14824 men and women aged 42-82 years, during mean follow-up of 1.9 years (SD 0.7), there were 121 incident fractures that needed admission, including 31 hip fractures. Men and women in the lowest 10% of the calcaneum BUA distribution had a relative risk of fracture of 4.44 (95% CI 2.24-8.89, p<0.0001) compared with those in the upper 30% of the distribution. A fall of about 1 SD in BUA (20 db/MHz) was associated with a relative risk of fracture of 1.95 (95% CI 1.50-2.52, p<0.0001), independent of age, sex, weight, height, cigarette smoking habit, and past history of fracture. BUA predicted fractures with consistent magnitude in subgroups stratified by sex, age 65 years or older and younger than 65 years, smoking habit, past history of fracture, and hip and non-hip fractures separately. The sex difference in fracture risk was largely accounted for by differences in BUA. INTERPRETATION Quantitative calcaneum ultrasound predicts total and hip fracture risk in men and women in a continuous relation. The challenge now is to identify interventions to improve bone health in the whole population.

Residential area deprivation predicts smoking habit independently of individual educational level and occupational social class. A cross sectional study in the Norfolk cohort of the European Investigation into Cancer (EPIC-Norfolk)

Objectives: To investigate the independent association between individual and area based measures of socioeconomic status and cigarette smoking habit. Design and setting: Cross sectional, population based study. Participants and methods: 12 579 men and 15 132 women aged 39–79 years living in the general community participating in the EPIC-Norfolk Study in 1993–1997. The association between social class, educational status, Townsend residential deprivation level, and cigarette smoking status was examined. Main outcome measures: Cigarette smoking status at baseline survey. Results: Social class, educational level, and residential deprivation level independently related to cigarette smoking habit in both men and women. Multivariate age adjusted odds ratios for current smoking in men were 1.62 (95% CI 1.45 to 1.81) for manual compared with non-manual social class, 1.32 (95% CI 1.17 to 1.48) for those with educational level less than O level compared with those with O level qualifications or higher and 1.84 (95% CI 1.62 to 2.08) for high versus low area deprivation level. For women, the odds ratios for current smoking for manual social class were 1.14 (95% CI 1.03 to 1.27); 1.31 (95% CI 1.18 to 1.46) for low educational level and 1.68 (95% CI 1.49 to 1.90) for high residential deprivation respectively. Conclusions: Residential deprivation level using the Townsend score, individual social class, and educational level all independently predict smoking habit in both men and women. Efforts to reduce cigarette smoking need to tackle not just individual but also area based factors. Understanding the specific factors in deprived areas that influence smoking habit may help inform preventive efforts.

Fruit and vegetable intake and population glycosylated haemoglobin levels: the EPIC-Norfolk Study.

Objective: To investigate whether self-reported frequency of fruit and vegetable consumption was associated with HbA1C levels in individuals not known to have diabetes, and what dietary and lifestyle factors might explain this association.Design: Cross-sectional study.Setting: The EPIC-Norfolk Study, a population-based cohort study of diet and chronic disease.Subjects and methods: A total of 2678 men and 3318 women (45–74 y) not known to have diabetes reported weekly consumption of fruit, green leafy vegetables and other vegetables.Results: Among men, 274 (10.2%) reported seldom or never eating fruit and 127 (4.7%) seldom or never eating green leafy vegetables. Corresponding numbers in women were 157 (4.7%) and 92 (2.8%), respectively. Participants who reported never or seldom having both fruit and green leafy vegetables had higher mean (s.d.) HbA1C measurements (5.43% (0.71)) than those who reported more frequent consumption (5.34% (0.67); P=0.046). Differences by category of fruit or green leafy vegetable consumption were not substantially changed after adjustment for saturated fat, dietary fibre and plasma vitamin C.Conclusion: These findings support the hypothesis that high intake of fruit and green leafy vegetables may influence glucose metabolism independent of dietary fibre or vitamin C alone and that increased consumption may contribute to the prevention of diabetes.Sponsorship: NJW is an MRC Clinician Scientist Fellow.European Journal of Clinical Nutrition (2001) 55, 342–348

Frequency of eating and concentrations of serum cholesterol in the Norfolk population of the European prospective investigation into cancer (EPIC-Norfolk): cross sectional study

Abstract Objectives: To examine the relation between self reported eating frequency and serum lipid concentrations in a free living population. Design: Cross sectional population based study. Setting: Norfolk, England. Participants: 14 666 men and women aged 45–75 years from the Norfolk cohort of the European prospective investigation into cancer (EPIC-Norfolk). Main outcome measures: Concentrations of blood lipids. Results: Mean concentrations of total cholesterol and low density lipoprotein cholesterol decreased in a continuous relation with increasing daily frequency of eating in men and women. No consistent relation was observed for high density lipoprotein cholesterol, body mass index, waist to hip ratio, or blood pressure. Mean cholesterol concentrations differed by about 0.25 mmol/l between people eating more than six times a day and those eating once or twice daily; this difference was reduced to 0.15 mmol/l after adjustment for possible confounding variables, including age, obesity, cigarette smoking, physical activity, and intake of energy and nutrients (alcohol, fat, fatty acids, protein, and carbohydrate). Conclusions: Concentrations of total cholesterol and low density lipoprotein cholesterol are negatively and consistently associated with frequency of eating in a general population. The effects of eating frequency on lipid concentrations induced in short term trials in animals and human volunteers under controlled laboratory conditions can be observed in a free living general population. We need to consider not just what we eat but how often we eat. What is already known on this topic Studies in animals and small human trials indicate that eating frequency is inversely related to serum lipid concentrations Few studies have examined this in a free living population under no dietary restrictions What this study adds In a free living population increased eating frequency was negatively and significantly associated with concentrations of total cholesterol and low density lipoprotein cholesterol This association was still present after adjustment for body mass index, physical activity, cigarette smoking, and dietary intake Mean age adjusted cholesterol concentrations differed by 0.25 mmol/l between people eating more than six times a day and those eating less than twice daily

Patterns of physical activity and ultrasound attenuation by heel bone among Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): population based study

Abstract Objectives: To study associations between patterns of physical activity and ultrasound attenuation by the heel bone in men and women. Design: Cross sectional, population based study. Setting: Norfolk. Participants: 2296 men and 2914 women aged 45-74 registered with general practices participating in European Prospective Investigation into Cancer (EPIC Norfolk). Results: Self reported time spent in high impact physical activity was strongly and positively associated with ultrasound attenuation by the heel bone, independently of age, weight, and other confounding factors. Men who reported participating in 2 hours/week of high impact activity had 8.44 dB/MHz (95% confidence interval 4.49 to 12.40) or 9.5%, higher ultrasound attenuation than men who reported no activity of this type. In women, the difference in ultrasound attenuation between those reporting any high impact activity and those reporting none was 2.41 dB/MHz (0.45 to 4.37) or 3.4% higher. In women this effect was similar in size to that of an age difference of four years. Moderate impact activity had no effect. However, climbing stairs was strongly independently associated with ultrasound attenuation in women (0.64 dB/MHz (0.19 to 1.09) for each additional five flights of stairs). There was a significant negative association in women between time spent watching television or video and heel bone ultrasound attenuation, which decreased by 0.08 dB/MHz (0.02 to 0.14) for each additional hour of viewing a week. Conclusions: High impact physical activity is independently associated with ultrasound attenuation by the heel bone in men and women. As low ultrasound attenuation has been shown to predict increased risk of hip fracture, interventions to promote participation in high impact activities may help preserve bone density and reduce the risk of fracture. However, in older people such interventions may be inappropriate as they could increase the likelihood of falls.

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.