Modifiable causes of premature death in middle-age in Western Europe: results from the EPIC cohort study.

BACKGROUND: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death. METHODS: We analysed data from 264,906 European adults from the EPIC prospective cohort study, aged between 40 and 70 years at the time of recruitment. Flexible parametric survival models were used to model risk of death conditional on risk factors, and survival functions and attributable fractions (AF) for deaths prior to age 70 years were calculated based on the fitted models. RESULTS: We identified 11,930 deaths which occurred before the age of 70. The AF for premature mortality for smoking was 31 % (95 % confidence interval (CI), 31-32 %) and 14 % (95 % CI, 12-16 %) for poor diet. Important contributions were also observed for overweight and obesity measured by waist-hip ratio (10 %; 95 % CI, 8-12 %) and high blood pressure (9 %; 95 % CI, 7-11 %). AFs for physical inactivity and excessive alcohol intake were 7 % and 4 %, respectively. Collectively, the AF for all six risk factors was 57 % (95 % CI, 55-59 %), being 35 % (95 % CI, 32-37 %) among never smokers and 74 % (95 % CI, 73-75 %) among current smokers. CONCLUSIONS: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed.

Smoking as a major risk factor for cervical cancer and pre-cancer: results from the EPIC cohort.

A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case-control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV-2). Cervical samples were not available for HPV-DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case-control studies. In the cohort analyses smoking status, duration and intensity showed a two-fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two-fold reduced risk. In the nested case-control study, consistent associations were observed after adjustment for HPV, CT and HHV-2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation.

Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations.

Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up, among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined. We estimated flavonoid intake at baseline from validated dietary questionnaires using a database developed from Phenol-Explorer and USDA databases. We used country-specific Prentice-weighted Cox regression models and random-effects meta-analysis methods to estimate HRs. Among the flavanol subclass, we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models (all P-trend < 0.05). We also observed significant trends for the intakes of proanthocyanidin dimers (HR for the highest vs. the lowest quintile: 0.81; 95% CI: 0.71, 0.92; P-trend = 0.003) and trimers (HR: 0.91; 95% CI: 0.80, 1.04; P-trend = 0.07) but not for proanthocyanidins with a greater polymerization degree. Among the flavonol subclass, myricetin (HR: 0.77; 95% CI: 0.64, 0.93; P-trend = 0.001) was associated with a lower incidence of T2D. This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers, proanthocyanidins with a low polymerization degree, and the flavonol myricetin and incident T2D. These results suggest that individual flavonoids have different roles in the etiology of T2D.

Meat consumption and mortality--results from the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. RESULTS: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. CONCLUSIONS: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.

Dietary flavonoid and lignan intake and mortality in a Spanish cohort.

BACKGROUND: Dietary flavonoids and lignans may protect against several chronic diseases, but there is little evidence on the relationship between flavonoid and lignan intake and mortality. We investigated the association between both all-cause and specific-cause mortality and intake of flavonoids and lignans in the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC-Spain) cohort. METHODS: The EPIC-Spain study follows 40,622 participants (38% men) aged 29-69 years. A validated diet history questionnaire was administered at recruitment. A food composition database was compiled based on US Department of Agriculture and Phenol-Explorer databases. Cox proportional hazards models, adjusted for confounders, were used in the analyses. RESULTS: During a mean follow-up of 13.6 years, 1915 deaths were reported, with 416 from cardiovascular diseases (CVDs) and 956 from cancer. After adjustment for several potential confounders, the hazard ratios (HRs) for the highest versus the lowest quintile of dietary flavanone and flavonol intakes were 0.60 (95% confidence interval = 0.38-0.94) and 0.59 (0.40-0.88). Total flavonoid intake was also associated with a decrease in all-cause mortality (0.71 [0.49-1.03]). Lignan intake was not associated with all-cause mortality. In cause-specific mortality analyses, using competing risk regressions, doubling total flavonoid intake was inversely related to mortality from CVD (HR for log2 0.87 [0.77-0.98]), but not to mortality from either cancer (HR for log2 0.96 [0.89-1.04]) or other causes (HR for log2 0.97 [0.87-1.09]). CONCLUSIONS: A diet high in flavonoids, particularly in flavanones and flavonols, is associated with a reduction in all-cause mortality, mainly of mortality from CVD.

Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries.

OBJECTIVE: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN: Population based cohort study. SETTING: European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS: 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE: Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS: After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P<0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P<0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P<0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. CONCLUSIONS: In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.

Accuracy of ImmunoCAP Rapid in the diagnosis of allergic sensitization in children between 1 and 14 years with recurrent wheezing: the IReNE study.

It is estimated that at least one out of three children with recurrent wheezing is atopic. Reliable diagnostic tools are needed in primary care that allow for adequate identification of these children. The purpose of this study was to assess the value of ImmunoCAP Rapid (ICR) Wheeze-Rhinitis Child in the identification of atopy with the use of 10 selected allergens in children with recurrent episodes of wheezing. A multicenter population study is based on primary care. It included children managed consecutively at the health center, who had three or more episodes of wheezing, at least one of them in the last 12 months. Each child completed a physical examination, an epidemiological survey, one capillary blood sampling (110 microl) for ICR, and one venous blood sampling for determination of Phadiatop Infant, total IgE and 10 specific IgE measurements. The children were identified as atopic, based on their clinical signs and symptoms and at least one positive specific IgE (0.35 kU(A)/l or higher), before knowing the results of ICR, Phadiatop Infant and total IgE. ICR was read by two independent observers. Six classes were evaluated, negative without any color and five positive degrees of pink-red color. Two hundred and fifteen children aged between 1 and 14 years were studied (138 boys); 50.7% were identified as atopic, 39.1% were sensitized only to inhalant allergens, 6.5% to food allergens and 5.1% to both. The predominant allergen was the dust mite (39.3%). For ICR, there were 2134 valid double observations. The Kappa index, comparing the negative results vs. any positive result, was 0.91 (95% CI: 0.88-0.94). The intraclass correlation coefficient was 0.98 (95% CI: 0.98-0.99). In the identification of a child as atopic, the positive post-test probability of ICR depended on the color degrees considered: 88.4% for any positive and 97.6% for the most intense tones. The positive post-test probability of Phadiatop Infant and total IgE was 95.6% and 68.2% respectively. ICR showed good reliability for the most prevalent allergen, the dust mite, with a sensitivity of 90.5% (95% CI: 82.1-95.8) and specificity of 88.5% (95% CI: 81.7-93.4). The analysis of the other allergens was limited by the small number of sensitized children. The analysis of receiver operating characteristic curves revealed an area under the curve of 0.84 (95% CI 0.80-0.88) for the cut-off point of specific IgE of 0.35 kU(A)/l and of 0.94(CI 0.91-0.97) for 2 kU(A)/l. A greater intensity of color of the lines of ICR was related to higher levels of specific IgE in blood. ICR is a reliable test for the identification of atopy in children, which identifies most children as atopic, and shows a good correlation in allergen-by-allergen identification. This suggests that it should be regarded as a first-rate tool, in the primary care clinic, for the evaluation of children with recurrent wheezing.

Parity, breastfeeding and risk of coronary heart disease: A pan-European case-cohort study.

OBJECTIVE: There is uncertainty about the direction and magnitude of the associations between parity, breastfeeding and the risk of coronary heart disease (CHD). We examined the separate and combined associations of parity and breastfeeding practices with the incidence of CHD later in life among women in a large, pan-European cohort study. METHODS: Data were used from European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD, a case-cohort study nested within the EPIC prospective study of 520,000 participants from 10 countries. Information on reproductive history was available for 14,917 women, including 5138 incident cases of CHD. Using Prentice-weighted Cox regression separately for each country followed by a random-effects meta-analysis, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD, after adjustment for age, study centre and several socioeconomic and biological risk factors. RESULTS: Compared with nulliparous women, the adjusted HR was 1.19 (95% CI: 1.01-1.41) among parous women; HRs were higher among women with more children (e.g., adjusted HR: 1.95 (95% CI: 1.19-3.20) for women with five or more children). Compared with women who did not breastfeed, the adjusted HR was 0.71 (95% CI: 0.52-0.98) among women who breastfed. For childbearing women who never breastfed, the adjusted HR was 1.58 (95% CI: 1.09-2.30) compared with nulliparous women, whereas for childbearing women who breastfed, the adjusted HR was 1.19 (95% CI: 0.99-1.43). CONCLUSION: Having more children was associated with a higher risk of CHD later in life, whereas breastfeeding was associated with a lower CHD risk. Women who both had children and breastfed did have a non-significantly higher risk of CHD.

Smoking and long-term risk of type 2 diabetes: the EPIC-InterAct study in European populations.

OBJECTIVE: The aims of this study were to investigate the association between smoking and incident type 2 diabetes, accounting for a large number of potential confounding factors, and to explore potential effect modifiers and intermediate factors. RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct is a prospective case-cohort study within eight European countries, including 12,403 cases of incident type 2 diabetes and a random subcohort of 16,835 individuals. After exclusion of individuals with missing data, the analyses included 10,327 cases and 13,863 subcohort individuals. Smoking status was used (never, former, current), with never smokers as the reference. Country-specific Prentice-weighted Cox regression models and random-effects meta-analysis were used to estimate hazard ratios (HRs) for type 2 diabetes. RESULTS: In men, the HRs (95% CI) of type 2 diabetes were 1.40 (1.26, 1.55) for former smokers and 1.43 (1.27, 1.61) for current smokers, independent of age, education, center, physical activity, and alcohol, coffee, and meat consumption. In women, associations were weaker, with HRs (95% CI) of 1.18 (1.07, 1.30) and 1.13 (1.03, 1.25) for former and current smokers, respectively. There was some evidence of effect modification by BMI. The association tended to be slightly stronger in normal weight men compared with those with overall adiposity. CONCLUSIONS: Former and current smoking was associated with a higher risk of incident type 2 diabetes compared with never smoking in men and women, independent of educational level, physical activity, alcohol consumption, and diet. Smoking may be regarded as a modifiable risk factor for type 2 diabetes, and smoking cessation should be encouraged for diabetes prevention.