Diet Quality Scores and Prediction of All-Cause, Cardiovascular and Cancer Mortality in a Pan-European Cohort Study.

Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors.

Evaluating the Applicability of Data-Driven Dietary Patterns to Independent Samples with a Focus on Measurement Tools for Pattern Similarity.

BACKGROUND: Diet is a key modifiable risk for many chronic diseases, but it remains unclear whether dietary patterns from one study sample are generalizable to other independent populations. OBJECTIVE: The primary objective of this study was to assess whether data-driven dietary patterns from one study sample are applicable to other populations. The secondary objective was to assess the validity of two criteria of pattern similarity. METHODS: Six dietary patterns-Western (n=3), Mediterranean, Prudent, and Healthy- from three published studies on breast cancer were reconstructed in a case-control study of 973 breast cancer patients and 973 controls. Three more internal patterns (Western, Prudent, and Mediterranean) were derived from this case-control study's own data. STATISTICAL ANALYSIS: Applicability was assessed by comparing the six reconstructed patterns with the three internal dietary patterns, using the congruence coefficient (CC) between pattern loadings. In cases where any pair met either of two commonly used criteria for declaring patterns similar (CC ≥0.85 or a statistically significant [P<0.05] Pearson correlation), then the true similarity of those two dietary patterns was double-checked by comparing their associations to risk for breast cancer, to assess whether those two criteria of similarity are actually reliable. RESULTS: Five of the six reconstructed dietary patterns showed high congruence (CC >0.9) to their corresponding dietary pattern derived from the case-control study's data. Similar associations with risk for breast cancer were found in all pairs of dietary patterns that had high CC but not in all pairs of dietary patterns with statistically significant correlations. CONCLUSIONS: Similar dietary patterns can be found in independent samples. The P value of a correlation coefficient is less reliable than the CC as a criterion for declaring two dietary patterns similar. This study shows that diet scores based on a particular study are generalizable to other populations.

Gaussian Graphical Models Identify Networks of Dietary Intake in a German Adult Population.

BACKGROUND: Data-reduction methods such as principal component analysis are often used to derive dietary patterns. However, such methods do not assess how foods are consumed in relation to each other. Gaussian graphical models (GGMs) are a set of novel methods that can address this issue. OBJECTIVE: We sought to apply GGMs to derive sex-specific dietary intake networks representing consumption patterns in a German adult population. METHODS: Dietary intake data from 10,780 men and 16,340 women of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort were cross-sectionally analyzed to construct dietary intake networks. Food intake for each participant was estimated using a 148-item food-frequency questionnaire that captured the intake of 49 food groups. GGMs were applied to log-transformed intakes (grams per day) of 49 food groups to construct sex-specific food networks. Semiparametric Gaussian copula graphical models (SGCGMs) were used to confirm GGM results. RESULTS: In men, GGMs identified 1 major dietary network that consisted of intakes of red meat, processed meat, cooked vegetables, sauces, potatoes, cabbage, poultry, legumes, mushrooms, soup, and whole-grain and refined breads. For women, a similar network was identified with the addition of fried potatoes. Other identified networks consisted of dairy products and sweet food groups. SGCGMs yielded results comparable to those of GGMs. CONCLUSIONS: GGMs are a powerful exploratory method that can be used to construct dietary networks representing dietary intake patterns that reveal how foods are consumed in relation to each other. GGMs indicated an apparent major role of red meat intake in a consumption pattern in the studied population. In the future, identified networks might be transformed into pattern scores for investigating their associations with health outcomes.

Main nutrient patterns are associated with prospective weight change in adults from 10 European countries.

PURPOSE: Various food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults. METHODS: This study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders. RESULTS: Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant. CONCLUSIONS: We identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.

Plasma Ascorbic Acid, A Priori Diet Quality Score, and Incident Hypertension: A Prospective Cohort Study.

Vitamin C may reduce risk of hypertension, either in itself or by marking a healthy diet pattern. We assessed whether plasma ascorbic acid and the a priori diet quality score relate to incident hypertension and whether they explain each other's predictive abilities. Data were from 2884 black and white adults (43% black, mean age 35 years) initially hypertension-free in the Coronary Artery Risk Development in Young Adults Study (study year 10, 1995-1996). Plasma ascorbic acid was assessed at year 10 and the diet quality score at year 7. Eight-hundred-and-forty cases of hypertension were documented between years 10 and 25. After multiple adjustments, each 12-point (1 SD) higher diet quality score at year 7 related to mean 3.7 µmol/L (95% CI 2.9 to 4.6) higher plasma ascorbic acid at year 10. In separate multiple-adjusted Cox regression models, the hazard ratio of hypertension per 19.6-µmol/L (1 SD) higher ascorbic acid was 0.85 (95% CI 0.79-0.92) and per 12-points higher diet score 0.86 (95% CI 0.79-0.94). These hazard ratios changed little with mutual adjustment of ascorbic acid and diet quality score for each other, or when adjusted for anthropometric variables, diabetes, and systolic blood pressure at year 10. Intake of dietary vitamin C and several food groups high in vitamin C content were inversely related to hypertension, whereas supplemental vitamin C was not. In conclusion, plasma ascorbic acid and the a priori diet quality score independently predict hypertension. This suggests that hypertension risk is reduced by improving overall diet quality and/or vitamin C status. The inverse association seen for dietary but not for supplemental vitamin C suggests that vitamin C status is preferably improved by eating foods rich in vitamin C, in addition to not smoking and other dietary habits that prevent ascorbic acid from depletion.

Fruit and Vegetable Consumption and Changes in Anthropometric Variables in Adult Populations: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

BACKGROUND: Randomized controlled trials provide conflicting results on the effects of increased fruit and vegetable consumption on changes in body weight. We aimed to perform a systematic review and meta-analysis of prospective cohort studies on fruit and vegetable consumption in relation to changes in anthropometric measures. METHODS: PubMed and EMBASE were searched up to July 2015 for prospective studies reporting on habitual fruit and/or vegetable consumption in relation to changes in body weight or waist circumference or to risk of weight gain/overweight/obesity in adults. Random-effects meta-analysis was applied to pool results across studies. FINDINGS: Seventeen cohort studies (from 20 reports) including 563,277 participants met our inclusion criteria. Higher intake of fruits was inversely associated with weight change (decrease) (beta-coefficient per 100-g increment, -13.68 g/year; 95% CI, -22.97 to -4.40). No significant changes could be observed for combined fruit and vegetable consumption or vegetable consumption. Increased intake of fruits was inversely associated with changes (decrease) in waist circumference (beta: -0.04 cm/year; 95% CI, -0.05 to -0.02). Comparing the highest combined fruit & vegetable, fruit, and vegetable intake categories were associated with a 9%, 17%, and 17% reduced risk of adiposity (odds ratio [OR]: 0.91, 95% CI, 0.84 to 0.99), (OR: 0.83, 95% CI, 0.71 to 0.99), and (OR: 0.83, 95% CI, 0.70 to 0.99), respectively. CONCLUSION: This meta-analysis showed several inverse associations between fruit and vegetable intake and prospective improvements in anthropometric parameters, and risk of adiposity. The present meta-analysis seems to be limited by low study quality. Nevertheless, when combined with evolutionary nutrition and epidemiological modeling studies, these findings have public health relevance and support all initiatives to increase fruit and vegetable intake.

Potential Predictors of Plasma Fibroblast Growth Factor 23 Concentrations: Cross-Sectional Analysis in the EPIC-Germany Study.

BACKGROUND: Increased fibroblast growth factor 23 (FGF23), a bone-derived hormone involved in the regulation of phosphate and vitamin D metabolism, has been related to the development of cardiovascular disease (CVD) in chronic kidney disease patients and in the general population. However, what determines higher FGF23 levels is still unclear. Also, little is known about the influence of diet on FGF23. The aim of this study was therefore to identify demographic, clinical and dietary correlates of high FGF23 concentrations in the general population. METHODS: We performed a cross-sectional analysis within a randomly selected subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany comprising 2134 middle-aged men and women. The Human FGF23 (C-Terminal) ELISA kit was used to measure FGF23 in citrate plasma. Dietary data were obtained at baseline via validated food frequency questionnaires including up to 148 food items. RESULTS: Multivariable adjusted logistic regression showed that men had a 66% lower and smokers a 64% higher probability of having higher FGF23 (≥ 90 RU/mL) levels compared, respectively, with women and nonsmokers. Each doubling in parathyroid hormone, creatinine, and C-reactive protein was related to higher FGF23. Among the dietary factors, each doubling in calcium and total energy intake was related, respectively, to a 1.75 and to a 4.41 fold increased probability of having higher FGF23. Finally, each doubling in the intake of iron was related to an 82% lower probability of having higher FGF23 levels. Results did not substantially change after exclusion of participants with lower kidney function. CONCLUSIONS: In middle-aged men and women traditional and non-traditional CVD risk factors were related to higher FGF23 concentrations. These findings may contribute to the understanding of the potential mechanisms linking increased FGF23 to increased CVD risk.

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials.

BACKGROUND: In the Western world, dietary supplements are commonly used to prevent chronic diseases, mainly cardiovascular disease and cancer. However, there is inconsistent evidence on which dietary supplements actually lower risk of chronic disease, and some may even increase risk. We aim to evaluate the comparative safety and/or effectiveness of dietary supplements for the prevention of mortality (all-cause, cardiovascular, and cancer) and cardiovascular and cancer incidence in primary prevention trials. METHODS/DESIGN: We will search PubMed, EMBASE, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials, clinical trials.gov, and the World Health Organization International Trial Registry Platform. Randomized controlled trials will be included if they meet the following criteria: (1) minimum intervention period of 12 months; (2) primary prevention of chronic disease (is concerned with preventing the onset of diseases and conditions); (3) minimum mean age ≥18 years (maximum mean age 70 years); (4) intervention(s) include vitamins (beta-carotene, vitamin A, B vitamins, Vitamin C, Vitamin D, Vitamin E, and multivitamin supplements); fatty acids (omega-3 fatty acids, omega-6 fatty acids, monounsaturated fat); minerals (magnesium, calcium, selenium, potassium, iron, zinc, copper, iodine; multiminerals); supplements containing combinations of both vitamins and minerals; protein (amino acids); fiber; prebiotics; probiotics; synbiotics; (5) supplements are orally administered as liquids, pills, capsules, tablets, drops, ampoules, or powder; (6) report results on all-cause mortality (primary outcome) and/or mortality from cardiovascular disease or cancer, cardiovascular and/or cancer incidence (secondary outcomes). Pooled effects across studies will be calculated using Bayesian random effects network meta-analysis. Sensitivity analysis will be performed for trials lasting ≥5 years, trials with low risk of bias, trials in elderly people (≥65 years), ethnicity, geographical region, and trials in men and women. The results of the corresponding fixed effects models will also be compared in sensitivity analyses. DISCUSSION: This is a presentation of the study protocol only. Results and conclusions are pending completion of this study. Our systematic review will be of great value to consumers of supplements, healthcare providers, and policy-makers, regarding the use of dietary supplements. PROSPERO: CRD42014014801 .

Chocolate-candy consumption and 3-year weight gain among postmenopausal U.S. women.

OBJECTIVE: To test the hypothesis that greater chocolate-candy intake is associated with more weight gain in postmenopausal women. METHODS: A prospective cohort study involved 107,243 postmenopausal American women aged 50-79 years (mean = 60.7) at enrollment in the Women's Health Initiative, with 3-year follow-up. Chocolate-candy consumption was assessed by food frequency questionnaire, and body weight was measured. Linear mixed models, adjusted for demographic, socio economic, anthropomorphic, and behavioral variables, were used to test our main hypotheses. RESULTS: Compared with women who ate a 1 oz (∼28 g) serving of chocolate candy <1 per month, those who ate this amount 1 per month to <1 per week, 1 per week to < 3 per week and ≥3 per week showed greater 3-year prospective weight gains (kg) of 0.76 (95% CI: 0.66, 0.85), 0.95 (0.84, 1.06), and 1.40 (1.27, 1.53), respectively, (P for linear trend<0.0001). Each additional 1 oz/day was associated with a greater 3-year weight gain (kg) of 0.92 (0.80, 1.05). The weight gain in each chocolate-candy intake level increased as BMI increased above the normal range (18.5-25 kg/m(2)), and was inversely associated with age. CONCLUSIONS: Greater chocolate-candy intake was associated with greater prospective weight gain in this cohort of postmenopausal women.

Plasma fibroblast growth factor 23 and risk of cardiovascular disease: results from the EPIC-Germany case-cohort study.

Increased fibroblast growth factor 23 (FGF23) concentrations have emerged as a novel risk factor for heart failure and stroke but not for myocardial infarction (MI). Yet, most studies on MI were conducted in coronary artery disease (CAD) patients and the elderly. Evidence is unclear in subjects without CAD and for stroke subtypes. We investigated the relationships between FGF23 and overall major cardiovascular endpoints, incident MI, ischemic (IS) and haemorrhagic stroke (HS) in middle-aged adults without pre-existing cardiovascular disease. We used a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition-Germany, including a randomly drawn subcohort (n = 1,978), incident MI (n = 463) and stroke cases (n = 359 IS; n = 88 HS) identified during a mean follow-up of 8.2 years. Compared with participants with FGF23 levels in the lowest quartile, those in the highest quartile had a 36% increased risk for cardiovascular events [hazard ratio: 1.36, 95% confidence interval (CI): 1.02-1.82] after adjustment for established cardiovascular risk factors, patahyroid hormone and 25-hydroxyvitamin D3 levels, dietary calcium and phosphorus intake, and kidney function. However, sub-analyses revealed significant relationships with risk of MI and HS, but not IS. Compared with the lowest quartile, individuals in the top two FGF23 quartiles had a 1.62 (95% CI 1.07-2.45) fold increased risk for MI and a 2.61 (95% CI 1.23-5.52) fold increase for HS. Increased FGF23 emerged as a risk factor for both MI and HS. Further studies are warranted to confirm these results and to identify underlying mechanisms.

Untargeted metabolic profiling identifies altered serum metabolites of type 2 diabetes mellitus in a prospective, nested case control study.

BACKGROUND: Application of metabolite profiling could expand the etiological knowledge of type 2 diabetes mellitus (T2D). However, few prospective studies apply broad untargeted metabolite profiling to reveal the comprehensive metabolic alterations preceding the onset of T2D. METHODS: We applied untargeted metabolite profiling in serum samples obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 300 individuals who developed T2D after a median follow-up time of 6 years and 300 matched controls. For that purpose, we used ultraperformance LC-MS with a protocol specifically designed for large-scale metabolomics studies with regard to robustness and repeatability. After multivariate classification to select metabolites with the strongest contribution to disease classification, we applied multivariable-adjusted conditional logistic regression to assess the association of these metabolites with T2D. RESULTS: Among several alterations in lipid metabolism, there was an inverse association with T2D for metabolites chemically annotated as lysophosphatidylcholine(dm16:0) and phosphatidylcholine(O-20:0/O-20:0). Hexose sugars were positively associated with T2D, whereas higher concentrations of a sugar alcohol and a deoxyhexose sugar reduced the odds of diabetes by approximately 60% and 70%, respectively. Furthermore, there was suggestive evidence for a positive association of the circulating purine nucleotide isopentenyladenosine-5'-monophosphate with incident T2D. CONCLUSIONS: This study constitutes one of the largest metabolite profiling approaches of T2D biomarkers in a prospective study population. The findings might help generate new hypotheses about diabetes etiology and develop further targeted studies of a smaller number of potentially important metabolites.

Relationship between N-terminal pro-brain natriuretic peptide, obesity and the risk of heart failure in middle-aged German adults.

BACKGROUND: Both high concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and obesity are related to higher heart failure risk. However, inverse relationships between NT-proBNP and obesity have been reported. Therefore, it was investigated whether the association between NT-proBNP and the risk of heart failure differed according to obesity status. METHODS: A case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, comprising a random sub-cohort (non-cases = 1,150, cases = 13, mean age: 50.5±9.0 years) and heart failure cases outside the sub-cohort (n = 197). Weighted Cox proportional hazards regression was used to examine the association between NT-proBNP and heart failure risk during a mean follow-up time of 8 years. Stratified analyses were performed according to obesity status as defined by body mass index (<30 kg/m2 versus ≥30 kg/m2). RESULTS: Overall, NT-proBNP was associated with higher risk of heart failure after multivariable adjustment (hazard ratio (HR) and 95% confidence interval (CI): 2.56 (1.49-4.41) for the top versus bottom tertile of NT-proBNP, ptrend:<0.01). In stratified analyses, the shape of association was linear in non-obese and U-shaped in obese participants: HRs (95%CI) from the first to the third tertile of NT-proBNP for non-obese: reference, 1.72 (0.85-3.49), 2.72 (1.42-5.22), and for obese: 3.29 (1.04-10.40), reference, 3.74 (1.52-9.21). CONCLUSIONS: Although high circulating concentrations of NT-proBNP were positively associated with incident heart failure in the entire sample, the association differed according to obesity status. In obese, an increased risk of heart failure was also observed in those with low NT-proBNP concentrations. If confirmed, this observation warrants further investigation to understand underlying pathophysiological mechanisms.

Nutrient patterns and their food sources in an International Study Setting: report from the EPIC study.

BACKGROUND: Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses. METHODOLOGY/PRINCIPAL FINDINGS: We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores. CONCLUSION/SIGNIFICANCE: The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level.

Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study.

UNLABELLED: The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between prediagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and the risk of HCC in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRRs) of HCC associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of prediagnostic 25(OH)D were calculated using conditional logistic regression. Higher 25(OH)D levels were associated with a 49% reduction in the risk of HCC (highest versus lowest tertile: multivariable IRR = 0.51, 95% confidence interval [CI], 0.26 to 0.99; Ptrend = 0.04; per 10 nmol/L increase: IRR = 0.80, 95% CI, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of preexisting liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. CONCLUSION: In this prospective study on western European populations, serum levels of 25(OH)D were inversely associated with the risk of HCC. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required.

Plasma fibroblast growth factor 23, parathyroid hormone, 25-hydroxyvitamin D3, and risk of heart failure: a prospective, case-cohort study.

CONTEXT: Bone mineral metabolism may play a role in the development of heart failure (HF). OBJECTIVE: The aim of the study was to investigate the relationships of plasma fibroblast growth factor (FGF) 23, PTH, and 25-hydroxyvitamin D3 [25(OH)D3] with incident congestive HF in a population-based cohort of men and women aged 40-65 and 35-65 years, respectively, at baseline. DESIGN: We conducted a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, including a randomly drawn sample of the total cohort free of HF and all incident HF cases that occurred during a mean follow-up of 8.2 ± 1.6 years. PARTICIPANTS AND SETTING: A total of 221 incident congestive HF cases and 1228 individuals free of HF were included in the study. MAIN OUTCOME MEASURES: Incident congestive HF was measured. RESULTS: In a multivariable model, each doubling of FGF23 [ie, per log (base 2) unit higher FGF23] was associated with a 29% higher HF risk (hazard ratio, 1.29 [95% confidence interval (CI), 1.07-1.56]). After multivariable adjustment, including estimated glomerular filtration rate, PTH was not related to HF risk (hazard ratio per doubling of PTH, 1.21 [95% CI, 0.99-1.48]). However, an interaction was observed between PTH and obesity, suggesting a relationship with HF risk in obese, but not in nonobese individuals. The hazard ratio for HF per doubling of 25(OH)D3 was 1.02 (95% CI, 0.73-1.41). CONCLUSIONS: Our findings provide epidemiological evidence for a positive relationship between FGF23 and risk of HF. The role of PTH in the development of HF remains unclear, in particular in obese individuals, until further confirmation in other studies. 25(OH)D3 was not related to HF.

Adiponectin and risk of stroke: prospective study and meta-analysis.

BACKGROUND AND PURPOSE: The favorable cardiovascular effects attributed to adiponectin may lower risk of stroke. We investigated this in a prospective study and meta-analysis. METHODS: A case-cohort study nested within the Potsdam cohort of the European Prospective Investigation into Cancer was performed, with 170 incident cases of ischemic stroke and a randomly selected subcohort of 2155 participants without major cardiovascular disease at baseline. A random-effects dose-response meta-analysis was performed on prospective studies reporting on adiponectin and incident stroke in healthy populations up to April 2013, identified through MEDLINE and EMBASE. RESULTS: In European Prospective Investigation into Cancer-Potsdam, after adjustment for cardiovascular risk factors, the hazard ratio of ischemic stroke per 5-µg/mL higher total-adiponectin was 1.10 (95% confidence interval, 0.89-1.37). Participants with higher total-adiponectin had higher high-density lipoprotein-cholesterol and lower high-sensitivity C-reactive protein and triglyceride levels, and had less often diabetes mellitus. Additional adjustment for these putative mediators yielded a hazard ratio of 1.31 (95% confidence interval, 1.04-1.64). Nine studies (19,259 participants, 2960 cases), including European Prospective Investigation into Cancer-Potsdam, were meta-analyzed. Pooling relative risks adjusted for cardiovascular risk factors not including putative mediators indicated moderate between-study heterogeneity (I2=52.2%). This was explained by the smallest study, and the pooled relative risk (95% confidence interval) before and after its exclusion was 1.03 (0.98-1.08) and 0.99 (0.96-1.01) per 5 µg/mL, respectively. The pooled relative risk (95% confidence interval) additionally adjusted for potential mediators was 1.08 (1.01-1.15) and 1.05 (1.00-1.11) before and after excluding the same study, respectively. CONCLUSIONS: Adiponectin is not associated with risk of stroke. If anything, adiponectin relates directly to stroke risk after controlling for risk factors that favorably correlate with adiponectin.

Dietary, lifestyle, and genetic determinants of vitamin D status: a cross-sectional analysis from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study.

PURPOSE: Considerable variation in 25-hydroxyvitamin D (25(OH)D) in populations worldwide that seems to be independent of latitude has been reported. Therefore, we aimed to assess vitamin D status of a mid-aged German general population and to identify its dietary, lifestyle, anthropometric, and genetic determinants. METHODS: 25(OH)D concentrations were measured by LC-MS/MS in plasma samples of a random subcohort of the German arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) comprising 2,100 subjects aged 35-65 years. Associations between potential predictors and 25(OH)D were assessed by linear regression models. RESULTS: 32.8% of the variance in 25(OH)D was explained by a multivariable regression model, with season being the by far strongest predictor (semi-partial R²: 14.6%). Sex, waist circumference, leisure time physical activity, smoking, polymorphisms in the GC, CYP2R1, and DHCR7 genes, supplement use, exogenous hormone use, alcohol consumption, egg consumption, and fish consumption were significantly associated with 25(OH)D concentrations as well. However, none of these factors explained >2.3% of the variance in 25(OH)D. CONCLUSION: Even with a comprehensive set of genetic, anthropometric, dietary, and lifestyle correlates, not more than 32.8% of the variation in 25(OH)D could be explained in the EPIC-Germany study, implying that vitamin D prediction scores may not provide an appropriate proxy for measured 25(OH)D. Food intake was only a weak predictor of 25(OH)D concentrations, while a strong seasonal fluctuation in 25(OH)D was shown.

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.

The association between dietary flavonoid and lignan intakes and incident type 2 diabetes in European populations: the EPIC-InterAct study.

OBJECTIVE: To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations. RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis. RESULTS: In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77-1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72-1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69-0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68-0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57-0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes. CONCLUSIONS: Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.