Body mass index and body fat distribution and new-onset atrial fibrillation: Substudy of the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk) study

Background and aimObesity 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 resultsParticipants 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<0.001), whereas for women in the highest BMI quintile, HR: 1.52 (CI 1.23–1.88, p for trend<0.001). Further, for men in the highest WHR quintile, HR: 1.31 (CI 1.09–1.57, p for trend: 0.01), whereas for women in the highest WHR quintile, HR: 1.12 (CI 0.90–1.41, p for trend: 0.17). The change in BMI and WHR was similar in participants with or without new-onset AF.ConclusionsAn increased body mass, as measured by BMI, is associated with an increased risk of developing new-onset AF. More abdominal fat distribution, as measured by WHR, is associated with an increased risk of developing new-onset AF in men but not in women.     

Fibrinogen and cigarette smoking in men and women in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population.

BACKGROUND: Plasma fibrinogen may be an independent risk factor for cardiovascular disease. Cigarette smoking is a well-recognized determinant of plasma fibrinogen however it remains unclear how fibrinogen levels relate to the degree and duration of smoking, or to time since smoking cessation. METHODS: In a population-based study of 11 059 men and women aged 45-74 years, we examined the cross-sectional relationship between plasma fibrinogen and cigarette smoking habit. RESULTS: Mean fibrinogen concentrations were higher in current smokers compared to non-current smokers (men: 3.13+/-0.77 versus 2.80+/-0.71 g/l, P<0.0001; women: 3.03+/-0.72 versus 2.95+/-0.71 g/l, P=0.01), independent of age, body mass index and hormone replacement therapy in women In men, fibrinogen concentrations declined with years since stopping smoking but remained higher than in life-long non-smokers for 15 years. No relationship between fibrinogen and duration of smoking cessation was observed in women. On multivariate analysis, age, body mass index, use of hormone-replacement therapy, smoking status and pack-years of smoking were independent predictors of plasma fibrinogen. CONCLUSIONS: Plasma fibrinogen is strongly associated with cigarette smoking with a dose-response relationship with total pack-years of smoking. In men who stop smoking plasma fibrinogen may remain elevated for several years after cessation.     

Microalbuminuria and stroke in a British population: the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study

OBJECTIVES: To examine the relationship between microalbuminuria and incident stroke in the general population. DESIGN: Population-based prospective cohort study. SETTING: Participants were recruited in a primary care setting from 35 participating general practice units in Norfolk, UK. SUBJECTS AND MAIN OUTCOME MEASURES: The study population consisted of 23,630 individuals aged 40-79 years recruited between 1993 and 1997 for the EPIC-Norfolk Study and followed up for an average of 7.2 years. Random spot urine specimens were collected at baseline and albumin-to-creatinine ratio measured. Participants were categorized into normoalbuminuria, microalbuminuria and macroalbuminuria groups. During follow-up, the main end point was stroke incidence (fatal and nonfatal), ascertained from the UK Office for National Statistics and from the National Health Service Health District database of all hospital admissions. RESULTS: A total of 246 stroke events occurred during follow-up [crude incidence rate of stroke, 1.5 per 1000 person years (pyrs)]. The age-adjusted incidence of stroke increased significantly across categories of baseline albuminuria (0.9, 1.1 and 1.4/1000 pyrs for tertiles of normoalbuminuria, 2.6/1000 pyrs for microalbuminuria, and 6/1000 pyrs for macroalbuminuria in the total population, P < 0.001 for trend). In all women and men, the multivariate hazard ratio [95% confidence interval (CI)] for stroke associated with microalbuminuria was 1.49 (1.13-2.14) and macroalbuminuria 2.43 (1.11-6.26). After stratifying by stroke subtype, microalbuminuria was only independently predictive of ischaemic stroke, with hazard ratio (95% CI) of 2.01 (1.29-3.31). CONCLUSION: Microalbuminuria is independently associated with approximately 50% increased risk of stroke in the general population. Microalbuminuria may be useful in identifying those at increased risk of stroke in the general population.     

Anthropometric and dietary determinants of blood pressure in over 7000 Mediterranean women: the European Prospective Investigation into Cancer and Nutrition-Florence cohort

BACKGROUND: Anthropometric characteristics and dietary habits are widely recognized to influence blood pressure. We evaluated their role in a large series of Mediterranean adult women. METHODS: In Florence, in the European Prospective Investigation into Cancer and Nutrition, we recruited 10 083 women, aged 35-64 years. Detailed information on diet, lifestyle, physical activity, and medical history were collected. Anthropometric indices and systolic and diastolic blood pressures were measured at recruitment using standardized procedures. Overall, after excluding those women who reported a clinical diagnosis of hypertension and/or an antihypertensive treatment and those without measurements, 7601 women were available for analyses with an average systolic and diastolic blood pressure value of 123.2+/-16.0 and 78.7+/-9.4 mmHg, respectively. RESULTS: Multivariate regression models showed that body mass index (P<0.0001) and waist circumference (>or=88 cm, P<0.0001), as well as processed meat, potatoes, and wine consumption, were directly associated with both systolic and diastolic values. In contrast, a high consumption of selected foods resulted inversely associated with systolic (total vegetables, yoghurt, and eggs), diastolic (olive oil) or both systolic and diastolic values (leafy vegetables, milk, coffee). Analyses performed on nutrients showed a positive association with alcohol and sodium intake, and an inverse one with potassium and micronutrients derived from fruits and vegetables. CONCLUSION: In this large series of women from Tuscany, Central Italy, we confirm the independent influence of anthropometric characteristics on blood pressure. The role of specific foods and nutrients in modulating blood pressure also emerged, suggesting a central role for lifestyle modifications in blood pressure control.     

Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case-control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50-4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20-3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98-2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88-2.36; P=0.05) and 2.05 (95% CI 1.23-3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34-0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.     

IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC)

Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02-1.86), P = 0.01, and 1.44 (95% CI 1.04-1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60-1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50-1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57-1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19-1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women.     

Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Aims/hypothesis

There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis.

Methods

Pre-diagnostic levels of HbA_1c and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer.

Results

Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA_1c levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [??6.5%, 48?mmol/mol] vs lowest [??5.4%, 36?mmol/mol] category), even for individuals with HbA_1c levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA_1c levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis.

Conclusions/interpretation

Our data on HbA_1c show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA_1c levels, relatively independently of obesity and insulin resistance??the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.     

Follow-up procedures in EPIC-Germany--data quality aspects. European Prospective Investigation into Cancer and Nutrition

With 475,000 participants throughout Europe, EPIC is one of the largest cohort studies investigating the association between diet and cancer and other chronic diseases. The German part of EPIC comprises about 53,000 participants in Potsdam (n = 27,616) and in Heidelberg (n = 25,546). In the German study centers, follow-up started in 1998 and will be continued in 2-year intervals over the next 10-15 years. To ensure high follow-up data quality at an European level, an international working group developed guidelines for endpoint data collection in every country. A follow-up phase in Germany comprises mailing of a questionnaire, tracing of individuals to whom mail could not be delivered, obtaining information on deceased participants including cause of death, and verifying self- reported diagnoses. Furthermore, activities aimed at motivating study participants are part of the follow-up. The first round of follow-up of those who entered the study in 1994 and 1995 included 8, 706 participants in Potsdam and 6,289 in Heidelberg. Due to a comprehensive and intensive reminder and tracing system, vital status of the study subjects is known from almost 100% in Potsdam and 99% in Heidelberg. Two years after baseline examination, and with twice as many addresses in Potsdam as in Heidelberg, addresses had to be traced or checked via population registry (13 versus 6%). Tracing, the application of different mailing strategies, and intensive reminder activities resulted in a 95% return of the questionnaire in Potsdam and 90% in Heidelberg. The system of follow-up data entry and control, including completion of missing information via telephone, verification of self-reports and causes of death, has been set up for EPIC-Germany and works efficiently and successfully. The aim of this paper is to describe the follow-up procedures in EPIC-Germany with a focus on the generation of valid and complete outcome data.     

Effect of age on the relationship of occupational social class with prevalence of modifiable cardiovascular risk factors and cardiovascular diseases. A population-based cross-sectional study from European Prospective Investigation into Cancer - Norfolk (EPIC-Norfolk)

BACKGROUND: Previous studies on cardiovascular risk profile in different socioeconomic status were focused on younger populations and many of them have not been able to take into account age and sex differences. OBJECTIVES: To investigate the relationship of occupational social class with the prevalence of cardiovascular disease risk factors and cardiovascular diseases in younger (<65 years) and older (>or=65 years) men and women. METHODS: A population-based-cross sectional study was conducted in a general community in Norfolk, United Kingdom. Participants were 23,085 men and women aged 40-79 years, recruited from general practice age-sex registers as part of European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk). The prevalence of cardiovascular risk factors and cardiovascular diseases were examined. Results: The prevalence of smoking was significantly higher in those in manual social classes particularly in the younger (<65) age group. Younger women in manual social classes were more likely to be smokers compared to older women in the same social class. Being in manual social classes was associated with higher cholesterol levels in women but lower cholesterol levels in men. Manual social class was associated with higher physical activity in those younger than 65 years but this association was reversed in those 65 years or older. CONCLUSION: Occupational social class is differently related to cardiovascular risk factors in individuals depending on their age and sex. This may reflect differences in behavior at work and leisure, which vary by sex and pre- and postretirement. Interventions to promote health and reduce social inequalities need to take age and gender into account.     

Interaction of vitamin C with the relation between smoking and obstructive airways disease in EPIC Norfolk. European Prospective Investigation into Cancer and Nutrition.

Previous studies have reported an association between plasma vitamin C levels and respiratory function, but have not examined the role of vitamin C as an effect modifier of the relation between cigarette smoking and obstructive airways disease (OAD). This question was investigated in a cross-sectional analysis of a population-based study of 3,714 males and 4,256 females aged 45-74 yrs. Undiagnosed OAD was defined as a forced expiratory volume in one second (FEV1) of <80% of the predicted value and FEV1/forced vital capacity of <70% without self-reported OAD. An increase of 20 micromol x L(-1) (or 1 SD) in plasma vitamin C concentration was associated with a 13% reduction in the risk of having OAD (adjusted odds ratio (OR) (95% confidence interval) 0.87 (0.77-0.98)). The OR for current smokers relative to never smokers within the lowest quintile of plasma vitamin C concentration was 5.93 (3.03-11.61). The risk in the upper four quintiles was 2.84 (1.92-4.19). Within the lowest quintile of plasma vitamin C concentration, the risk in former smokers was strongly related to the time since quitting (interaction significant, p=0.001). These findings support a protective role for vitamin C against the risk of obstructive airways disease and support the hypothesis that vitamin C may be an effect modifier for the adverse effects of smoking on the risk of obstructive airways disease.     

Measures of quality control in the German component of the EPIC study. European Prospective Investigation into Cancer and Nutrition

Quality control is an indispensable part of quality assurance in any study, intending to ensure high standards during data acquisition. The aim of this paper is to describe the measures of quality control undertaken in the German EPIC study centers and to present selected results of these procedures (EPIC = European Prospective Investigation into Cancer and Nutrition). For all data assessment tools applied in the German EPIC study, procedures were developed to monitor both the personnel as well as the technical instruments. These procedures combined quantitative and qualitative measurements of quality control. Interviewer performance was evaluated through direct observation and rated according to an evaluation score. Blood pressure and anthropometric measurements were both controlled through direct observation of measurement procedures as well as through periodical technical control of measurement devices. Blood sampling procedures were directly monitored and subsequent handling of the probes tightly recorded, including information on time sequence of work-up and room temperature. With these diverse control measurements and the obtained rating of assessment procedures a broad pool of information has been made available to support a critical evaluation of the data obtained in the EPIC study centers in Heidelberg and Potsdam.     

Factors explaining the difference of total homocysteine between men and women in the European Investigation Into Cancer and Nutrition Potsdam study

Interestingly, plasma total homocysteine (tHcy) concentration is consistently higher in men than in women. This observation deserves further investigations because elevated tHcy concentrations have been shown to be independently associated with coronary, peripheral, and cerebral vascular diseases. It was the aim of the present study to define major determinants of plasma tHcy in a healthy middle-aged German population under particular consideration of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, aged 40 to 65 years. Exclusion criteria were elevated creatinine levels in blood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine, testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate and homocysteine metabolism, was determined by polymerase chain reaction (PCR) with restriction enzyme analysis. In this population, plasma tHcy ranged from 5 to 46 micromol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, and 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No correlation was seen with vitamin B6. From the gender-related variables, tHyc correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was mainly explained by differences in fat-free mass, but also by estradiol concentrations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general population has a variety of determinants ranging from nutrition, internal metabolic parameters to gender-related variables.     

Body iron stores and risk of type 2 diabetes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study

Aims/hypothesis  

The aim of this study was to prospectively examine the association between body iron stores and risk of type 2 diabetes.