Linoleic acid in adipose tissue and the risk of myocardial infarction: a case-cohort study.

PURPOSE: We investigated risk of myocardial infarction (MI) associated with the content of linoleic acid (LA) in adipose tissue, a biomarker of long-term dietary intake of LA and a marker of endogenous LA exposure. METHODS: Between 1993 and 1997, 57,053 middle-aged subjects were included in the Danish Diet, Cancer and Health cohort. We performed a case-cohort study that included a random sample of the full cohort (n = 3167) and all incident MI cases appearing during 16 years of follow-up (n = 2819). Information on incident MI cases was obtained by linkage with Danish nationwide registries. Adipose tissue biopsies were taken from the buttocks of the participants, and their fatty acid composition was determined using gas chromatography. HRs (hazard ratios) with 95% confidence intervals (CIs) were used to describe the associations between content of LA in adipose tissue and the risk of MI. HRs were calculated using weighted Cox proportional hazards regression with robust variance. RESULTS: After adjustment for established risk factors of MI, adipose tissue content of LA was not associated with the risk of MI in men and women combined (quintiles 5 versus 1, HR, 1.03 (95% CI, 0.85-1.25), P-trend = 0.970) or in men and women separately (quintiles 5 versus 1, HR, 1.05 (95% CI, 0.83-1.33), P-trend = 0.871 and quintiles 5 versus 1, HR, 0.99 (95% CI 0.72-1.37), P-trend = 0.928, respectively). Investigating the association between LA and MI with a shorter, 5- or 10-year duration of follow-up provided similar results. CONCLUSION: Content of LA in adipose tissue was not associated with the risk of MI.

Substitutions between potatoes and other vegetables and risk of ischemic stroke.

PURPOSE: Intake of vegetables has been associated with a lower risk of ischemic stroke in observational studies controlling for total energy intake. However, adjustment for energy intake introduces a substitution aspect, which affects the interpretation of the results. We investigated replacement of potatoes with other vegetables, substitutions between vegetable subgroups, and risk of ischemic stroke and ischemic stroke subtypes. METHODS: The Danish Diet, Cancer and Health cohort included 57,053 participants aged 50-64 years at recruitment in 1993-1997. Diet was assessed from a validated 192-item semi-quantitative food frequency questionnaire. We calculated hazard ratios (HR) with 95% confidence intervals (CI) for the incidence of ischemic stroke using Cox proportional hazard regression. RESULTS: During 13.5 years of follow-up, 1879 cases of ischemic stroke were identified including 319 cases of large-artery atherosclerosis and 844 cases of small-vessel occlusion. The adjusted HR for total ischemic stroke associated with food substitutions of equal amounts (500 g/week) was 0.86 (95% CI 0.76, 0.97) for replacement of potatoes with fruiting vegetables and 0.92 (95% CI 0.84, 1.02) for replacement of potatoes with other root vegetables. The HR for replacing potatoes with the sum of other vegetables was 0.95 (95% CI 0.90, 1.00). Substitution of cabbage for either potatoes, fruiting vegetables or other root vegetables was associated with a statistically non-significant higher risk of ischemic stroke. The patterns of associations were similar for ischemic stroke subtypes and for equivalent substitutions using isocaloric amounts. CONCLUSION: Replacing potatoes with fruiting vegetables was associated with a lower risk of ischemic stroke.

Substitution of Milk with Whole-Fat Yogurt Products or Cheese Is Associated with a Lower Risk of Myocardial Infarction: The Danish Diet, Cancer and Health cohort.

BACKGROUND: Food-based dietary guidelines recommend replacement of whole-fat dairy products with low-fat variants based on data suggesting that diets high in saturated fat are associated with a higher risk of ischemic heart disease. However, the health effects of saturated fat may depend on the source. OBJECTIVES: The aim was to investigate substitutions between different subgroups of dairy products and the risk of myocardial infarction (MI). METHODS: Data were from the Danish Diet, Cancer and Health cohort and included 54,903 men and women aged 50-64 y at enrollment and without an MI diagnosis. Information about intake of dairy products was obtained by a semiquantitative food-frequency questionnaire. Incident MI cases were identified through nationwide registries. We used Cox proportional hazards regression to estimate associations between specified substitutions of dairy products and MI risk. RESULTS: During a median follow-up of 15.9 y, 3033 cases were identified. Whole-fat yogurt products in place of low-fat or whole-fat milk were associated with a lower risk of MI (HR: 0.89; 95% CI: 0.80, 0.99 per 200 g/d replaced; and HR: 0.87; 95% CI: 0.78, 0.98 per 200 g/d replaced, respectively). Substitution of 20 g/d of cheese for 200 g/d of low-fat or whole-fat milk was also associated with a lower risk of MI (HR: 0.96; 95% CI: 0.92, 0.99; and HR: 0.95; 95% CI: 0.89, 0.99, respectively). CONCLUSIONS: Among middle-aged Danish men and women, intake of whole-fat yogurt products or cheese in place of milk, regardless of fat content, was associated with a lower risk of development of MI.

Adipose tissue fatty acids present in dairy fat and risk of stroke: the Danish Diet, Cancer and Health cohort.

PURPOSE: The role of dairy fat for the risk of stroke is not yet clear. Adipose tissue reflects long-term fatty acid intake and metabolism. We, therefore, investigated associations for percentages of adipose tissue fatty acids, for which dairy products are a major source (12:0, 14:0, 14:1 cis-9, 15:0, 17:0, 18:1 trans-11 and 18:2 cis-9, trans-11), with incident total stroke and stroke subtypes. METHODS: We conducted a case-cohort study within the Danish Diet, Cancer and Health cohort, including all incident stroke cases (n = 2108) and a random sample of the total cohort (n = 3186). The fatty acid composition of adipose tissue biopsies was determined by gas chromatography and specific fatty acids were expressed as percentage of total fatty acids. Stroke cases were identified in the Danish National Patient Registry and the diagnoses were individually verified. RESULTS: We recorded 2108 stroke cases of which 1745 were ischemic, 249 were intracerebral hemorrhages and 102 were subarachnoid hemorrhages. We observed a lower rate of ischemic stroke for a higher adipose tissue percentage of 12:0, 14:0, 15:0, 17:0, 18:1 trans-11 and 18:2 cis-9, trans-11. Adipose tissue percentages of 15:0 and 18:1 trans-11 were also inversely associated with intracerebral hemorrhage, whereas no associations between the adipose tissue fatty acids and subarachnoid hemorrhage were observed. No associations between 14:1 cis-9 and ischemic or hemorrhagic stroke were found. CONCLUSIONS: Our results suggest that a larger percentage in adipose tissue of fatty acids for which dairy products are a major source is associated with a lower rate of ischemic stroke.

Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.

AIMS/HYPOTHESIS: Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. METHODS: We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution. RESULTS: No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined. CONCLUSIONS/INTERPRETATION: Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.

Substitutions of dairy product intake and risk of stroke: a Danish cohort study.

Low fat dairy products are part of dietary guidelines to prevent stroke. However, epidemiological evidence is inconclusive with regard to the association between dairy products and stroke. We therefore investigated associations for substitutions between dairy product subgroups and risk of total stroke and stroke subtypes. We included 55,211 Danish men and women aged 50-64 years without previous stroke. Baseline diet was assessed by a food frequency questionnaire. Cases were identified through a national register and subsequently verified. The associations were analyzed using Cox proportional hazard regression. During a median follow-up of 13.4 years, we identified 2272 strokes, of which 1870 were ischemic (318 large artery atherosclerotic, 839 lacunar, 102 cardioembolic, 98 other determined types, 513 of unknown type), 389 were hemorrhages (273 intracerebral, 116 subarachnoid) and 13 of unknown etiology. Substitution of semi-skimmed fermented milk or cheese for whole-fat fermented milk was associated with a higher rate of ischemic stroke [semi-skimmed fermented milk: hazard ratio (HR) = 1.20 (95% confidence interval (CI) 0.99-1.45), cheese: HR = 1.14 (95% CI 0.98-1.31) per serving/day substituted] and substitutions of whole-fat fermented milk for low-fat milk, whole-fat milk or buttermilk were associated with a lower rate [low-fat milk: HR = 0.85 (95% CI 0.74-0.99), whole-fat milk: HR = 0.84 (95% CI 0.71-0.98) and buttermilk: HR = 0.83 (95% CI 0.70-0.99)]. We observed no associations for substitutions between dairy products and hemorrhagic stroke. Our results suggest that intake of whole-fat fermented milk as a substitution for semi-skimmed fermented milk, cheese, buttermilk or milk, regardless of fat content, is associated with a lower rate of ischemic stroke.

Adherence to the Danish food-based dietary guidelines and risk of myocardial infarction: a cohort study.

OBJECTIVE: A direct way to evaluate food-based dietary guidelines is to assess if adherence is associated with development of non-communicable diseases. Thus, the objective was to develop an index to assess adherence to the 2013 Danish food-based dietary guidelines and to investigate the association between adherence to the index and risk of myocardial infarction (MI). DESIGN: Population-based cohort study with recruitment of participants in 1993-1997. Information on dietary intake was collected at baseline using an FFQ and an index ranging from 0 to 6 points was created to assess adherence to the 2013 Danish food-based dietary guidelines. MI cases were identified by record linkage to the Danish National Patient Register and the Causes of Death Register. Cox proportional hazards models were used to estimate hazard ratios (HR) of MI. SETTING: Greater areas of Aarhus and Copenhagen, Denmark. SUBJECTS: Men and women aged 50-64 years (n 55 021) from the Diet, Cancer and Health study. RESULTS: A total of 3046 participants were diagnosed with first-time MI during a median follow-up of 16·9 years. A higher Danish Dietary Guidelines Index score was associated with a lower risk of MI. After adjustment for potential confounders, the hazard of MI was 13 % lower among men with a score of 3-<4 (HR=0·87; 95 % CI 0·78, 0·96) compared with men with a score of <3. The corresponding HR among women was 0·76 (95 % CI 0·63, 0·93). CONCLUSIONS: Adherence to the 2013 Danish food-based dietary guidelines was inversely associated with risk of MI.

Adherence to a Healthy Nordic Diet and Risk of Stroke: A Danish Cohort Study.

BACKGROUND AND PURPOSE: Specific dietary patterns, including the Mediterranean diet, have been associated with stroke prevention. Our aim was to investigate whether adherence to a healthy Nordic diet, including fish, apples and pears, cabbages, root vegetables, rye bread, and oatmeal, was associated with risk of stroke. METHODS: Incident cases of stroke among 55 338 men and women from the Danish Diet, Cancer and Health cohort were identified from the Danish National Patient Register and verified by review of records. Cases of ischemic stroke were further subclassified based on etiology according to the TOAST classification system (Trial of Org 10172 in Acute Stroke Treatment). Information on diet was collected at baseline (1993-1997) using a semiquantitative food-frequency questionnaire. Cox proportional hazards models were used to estimate hazards ratios of total stroke and subtypes of ischemic and hemorrhagic stroke. RESULTS: During a median follow-up of 13.5 years, 2283 cases of incident stroke were verified, including 1879 ischemic strokes. Adherence to a healthy Nordic diet, as reflected by a higher Healthy Nordic Food Index score, was associated with a lower risk of stroke. The hazards ratio comparing an index score of 4 to 6 (high adherence) with an index score of 0 to 1 (low adherence) was 0.86 (95% confidence interval 0.76-0.98) for total stroke. Inverse associations were observed for ischemic stroke, including large-artery atherosclerosis. No trend was observed for hemorrhagic stroke; however, a statistically insignificant trend was observed for intracerebral hemorrhage. CONCLUSIONS: Our findings suggest that a healthy Nordic diet may be recommended for the prevention of stroke.

Evaluating the health impact of increased linseed consumption in the Danish population.

Consumption of linseeds has been suggested to have beneficial effects on human health. However, toxic constituents of linseed may compromise these benefits. We conducted a quantitative risk-benefit assessment to evaluate the overall health impact of increasing linseed intake up to 45 g/day in the Danish population (15-74 years). We quantified the risks associated with increased cadmium exposure and the benefits associated with increased intake of dietary fibre. Increased intakes of alpha-linoleic acid (ALA) were included in a sensitivity analysis. The overall health impact of different linseed intake scenarios was estimated in terms of Disability-Adjusted Life Years (DALYs). We found that the beneficial effects of linseed due to increased intake of dietary fibre outweighed the adverse health effects due to increased cadmium exposure in all scenarios. Up to 670 DALYs/100,000 individuals could be averted per year by increasing linseed consumption in the Danish population. The estimated beneficial health impact increased further when including ALA in the assessment. Different sources of uncertainty might affect the results, and more research is needed on both the health effects associated with intake of linseed and its constituents, and the bioavailability of ALA and cadmium from linseed to further improve the risk-benefit assessment.

Associations between red meat and risks for colon and rectal cancer depend on the type of red meat consumed.

Cancer prevention guidelines recommend limiting intake of red meat and avoiding processed meat; however, few studies have been conducted on the effects of specific red meat subtypes on colon cancer or rectal cancer risk. The study aim was to evaluate associations between intake of red meat and its subtypes, processed meat, fish, and poultry and risk for colon cancer or rectal cancer in the Danish Diet, Cancer and Health cohort study. We also evaluated whether fish or poultry should replace red meat intake to prevent colon cancer or rectal cancer. During follow-up (13.4 y), 644 cases of colon cancer and 345 cases of rectal cancer occurred among 53,988 participants. Cox proportional hazards models were used to compute incidence rate ratio (IRRs) and 95% CIs. No associations were found between intake of red meat, processed meat, fish, or poultry and risk for colon cancer or rectal cancer. The risk associated with specific red meat subtypes depended on the animal of origin and cancer subsite; thus, the risk for colon cancer was significantly elevated for higher intake of lamb [IRR(per 5g/d) = 1.07 (95% CI: 1.02-1.13)], whereas the risk for rectal cancer was elevated for higher intake of pork [IRR(per 25g/d) = 1.18 (95% CI: 1.02-1.36)]. Substitution of fish for red meat was associated with a significantly lower risk for colon cancer [IRR(per 25g/d) = 0.89 (95% CI: 0.80-0.99)] but not rectal cancer. Substitution of poultry for red meat did not reduce either risk. This study suggests that the risks for colon cancer and potentially for rectal cancer differ according to the specific red meat subtype consumed.

Determinants of non- response to a second assessment of lifestyle factors and body weight in the EPIC-PANACEA study.

BACKGROUND: This paper discusses whether baseline demographic, socio-economic, health variables, length of follow-up and method of contacting the participants predict non-response to the invitation for a second assessment of lifestyle factors and body weight in the European multi-center EPIC-PANACEA study. METHODS: Over 500.000 participants from several centers in ten European countries recruited between 1992 and 2000 were contacted 2-11 years later to update data on lifestyle and body weight. Length of follow-up as well as the method of approaching differed between the collaborating study centers. Non-responders were compared with responders using multivariate logistic regression analyses. RESULTS: Overall response for the second assessment was high (81.6%). Compared to postal surveys, centers where the participants completed the questionnaire by phone attained a higher response. Response was also high in centers with a short follow-up period. Non-response was higher in participants who were male (odds ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90; 2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had either a low (<18.5 kg/m2, 1.16 (1.09; 1.23)) or a high BMI (>25, 1.08 (1.06; 1.10); especially ≥30 kg/m2, 1.26 (1.23; 1.29)). CONCLUSIONS: Cohort studies may enhance cohort maintenance by paying particular attention to the subgroups that are most unlikely to respond and by an active recruitment strategy using telephone interviews.

Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition.

The consumption of meat and other foods of animal origin is a risk factor for several types of cancer, but the results for lymphomas are inconclusive. Therefore, we examined these associations among 411,097 participants of the European Prospective Investigation into Cancer and Nutrition. During a median follow-up of 8.5 years, 1,334 lymphomas (1,267 non-Hodgkin lymphoma (NHL) and 67 Hodgkin lymphomas) were identified. Consumption of red and processed meat, poultry, milk and dairy products was assessed by dietary questionnaires. Cox proportional hazard regression was used to evaluate the association of the consumption of these food groups with lymphoma risk. Overall, the consumption of foods of animal origin was not associated with an increased risk of NHLS or HL, but the associations with specific subgroups of NHL entities were noted. A high intake of processed meat was associated with an increased risk of B-cell chronic lymphocytic leukemia (BCLL) [relative risk (RR) per 50 g intake = 1.31, 95% confidence interval (CI) 1.06-1.63], but a decreased risk of follicular lymphomas (FL) (RR = 0.58; CI 0.38-0.89). A high intake of poultry was related to an increased risk of B-cell lymphomas (RR = 1.22; CI 1.05-1.42 per 10 g intake), FL (RR = 1.65; CI 1.18-2.32) and BCLL (RR = 1.54; CI 1.18-2.01) in the continuous models. In conclusion, no consistent associations between red and processed meat consumption and lymphoma risk were observed, but we found that the consumption of poultry was related to an increased risk of B-cell lymphomas. Chance is a plausible explanation of the observed associations, which need to be confirmed in further studies.

Ecological-level associations between highly processed food intakes and plasma phospholipid elaidic acid concentrations: results from a cross-sectional study within the European prospective investigation into cancer and nutrition (EPIC).

Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.

The association of education with body mass index and waist circumference in the EPIC-PANACEA study.

BACKGROUND: To examine the association of education with body mass index (BMI) and waist circumference (WC) in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHOD: This study included 141,230 male and 336,637 female EPIC-participants, who were recruited between 1992 and 2000. Education, which was assessed by questionnaire, was classified into four categories; BMI and WC, measured by trained personnel in most participating centers, were modeled as continuous dependent variables. Associations were estimated using multilevel mixed effects linear regression models. RESULTS: Compared with the lowest education level, BMI and WC were significantly lower for all three higher education categories, which was consistent for all countries. Women with university degree had a 2.1 kg/m2 lower BMI compared with women with lowest education level. For men, a statistically significant, but less pronounced difference was observed (1.3 kg/m2). The association between WC and education level was also of greater magnitude for women: compared with the lowest education level, average WC of women was lower by 5.2 cm for women in the highest category. For men the difference was 2.9 cm. CONCLUSION: In this European cohort, there is an inverse association between higher BMI as well as higher WC and lower education level. Public Health Programs that aim to reduce overweight and obesity should primarily focus on the lower educated population.

Intake of Unprocessed and Processed Meat and the Association with Cardiovascular Disease: An Overview of Systematic Reviews.

We conducted an overview of systematic reviews to summarize reviews of cohort studies on intake of unprocessed and processed meat and the risk of cardiovascular disease (CVD), coronary heart disease (CHD), and stroke. Systematic reviews of cohort studies published between January 2010 and August 2020 were identified through a systematic literature search in PubMed, Embase, and Web of Science. The quality of how each review was conducted was assessed and the overall confidence in the results of each review was rated using AMSTAR 2. The quality of evidence of each meta-analysis was graded using NutriGrade. Three reviews were included, with meta-analyses of unprocessed red meat and CVD (n = 1) and stroke (n = 2); unprocessed poultry and stroke (n = 1); and processed meat and CVD (n = 1), CHD (n = 1), and stroke (n = 3). The overall confidence in the results of each review was rated as critically low. The meta-evidence was graded moderate for a positive association between unprocessed red meat and stroke and moderate for a positive association between processed meat and CHD and stroke. For other associations the meta-evidence was graded as low or very low. In conclusion, the associations between unprocessed and processed meat with CVD and major subtypes of CVD have not been extensively investigated.

Intake of dairy products and associations with major atherosclerotic cardiovascular diseases: a systematic review and meta-analysis of cohort studies.

Specific types of dairy products may be differentially associated with atherosclerotic cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of cohort studies to summarize findings on the associations between total dairy product intake and intake of dairy product subgroups and the risk of major atherosclerotic CVDs in the general adult population. Our protocol was registered in PROSPERO (CRD42019125455). PubMed and Embase were systematically searched through 15 August 2019. For high versus low intake and dose-response meta-analysis, random-effects modelling was used to calculate summary risk ratios (RR). There were 13 cohort studies included for coronary heart disease (CHD), 7 for ischemic stroke and none for peripheral artery disease. High-fat milk was positively associated with CHD (RR 1.08 (95% confidence interval 1.00-1.16) per 200 g higher intake/day) and cheese was inversely associated with CHD (RR 0.96 (95% confidence interval 0.93-0.98) per 20 g higher intake/day). Heterogeneity, however, was observed in high versus low meta-analyses. Milk was inversely associated with ischemic stroke in high versus low meta-analysis only. In conclusion, this systematic review indicates a positive association of high-fat milk and an inverse association of cheese with CHD risk. The findings should be interpreted in the context of the observed heterogeneity.

Approaches for Health Effect Characterization in Risk-Benefit Assessment of Foods: A Comparative Case Study.

One of the challenges in quantitative risk-benefit assessment (RBA) of foods is the choice of approach for health effect characterization to estimate the health impact of dietary changes. The purpose of health effect characterization is to describe an association between intake of a food or food component and a health effect in terms of a dose-response relationship. We assessed the impact of the choice of approach for health effect characterization in RBA in two case studies based on substitution of (i) white rice by brown rice and (ii) unprocessed red meat by vegetables. We explored this by comparing the dose-response relations linking a health effect with (i) a food component present in the food, (ii) a food based on non-specified substitution analyses, and (iii) a food based on specified substitution analyses. We found that the choice of approach for health effect characterization in RBA may largely impact the results of the health impact estimates. Conducting the calculations only for a food component may neglect potential effects of the food matrix and of the whole food on the diet-disease association. Furthermore, calculations based on associations for non-specified substitutions include underlying food substitutions without specifying these. Data on relevant specified substitutions, which could reduce this type of bias, are unfortunately rarely available. Assumptions and limitations of the health effect characterization approaches taken in RBA should be documented and discussed, and scenario analysis is encouraged when multiple options are available.

Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD. RESULTS: There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, P-trend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk. CONCLUSIONS: In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.

Glycemic index, glycemic load, and risk of coronary heart disease: a pan-European cohort study.

BACKGROUND: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. OBJECTIVES: The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. METHODS: This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. RESULTS: After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) ≥25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI <25 [HR: 1.09 (95% CI: 0.98, 1.22) per 50 g/d) (P-interaction = 0.022). The GL-CHD association did not differ between men [HR: 1.19 (95% CI: 1.08, 1.30) per 50 g/d] and women [HR: 1.22 (95% CI: 1.07, 1.40) per 50 g/d] (test for interaction not significant). GI was associated with CHD risk only in the continuous model [HR: 1.04 (95% CI: 1.00, 1.08) per 5 units/d]. High available carbohydrate was associated with greater CHD risk [HR: 1.11 (95% CI: 1.03, 1.18) per 50 g/d]. High sugar intake was associated with greater CHD risk [HR: 1.09 (95% CI: 1.02, 1.17) per 50 g/d]. CONCLUSIONS: This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk.

A prospective analysis of the association between macronutrient intake and renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition.

Previous case-control studies have suggested that a high intake of animal foods and its associated nutrients are associated with an increased risk of renal cell carcinoma, although data from prospective studies are limited. We report here on the relationship between macronutrient intake and renal cell carcinoma incidence among 435,293 participants enrolled in the European Prospective Investigation into Cancer and Nutrition. Cox proportional hazard models were used to examine the association of dietary intake of fat, protein, carbohydrate, fiber and cholesterol and risk of renal cell carcinoma adjusted for age, sex, center, height, body mass index, physical activity, education, smoking, menopausal status, alcohol and energy intake. During an average 8.8 years of follow-up, 507 renal cell carcinoma cases occurred. Risk of renal cell carcinoma was not associated with macronutrient intake, including nutrients derived from animal sources. Our results indicate that macronutrient intake is not associated with risk of renal cell carcinoma in this cohort of European men and women.