Publications by authors named "Yvonne T van der Schouw"

384 Publications

Determinants of Food Choice and Perceptions of Supermarket-Based Nudging Interventions among Adults with Low Socioeconomic Position: The SUPREME NUDGE Project.

Int J Environ Res Public Health 2021 06 7;18(11). Epub 2021 Jun 7.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.

Nudging has received ample attention in scientific literature as an environmental strategy to promote healthy diets, and may be effective for reaching populations with low socioeconomic position (SEP). Therefore, the objective of this study was to investigate how the determinants of food choice shape the perceptions regarding supermarket-based nudging strategies among adults with low SEP. We conducted semi-structured interviews among fifteen adults with low SEP using a pre-defined topic list and visual examples of nudges. Interviews were recorded and transcribed verbatim and content analysis was used to analyse the data. The results show that food costs, convenience, healthiness, taste, and habits were frequently mentioned as determinants of food choice. However, the relative importance of these determinants seemed to be context-dependent. Interviewees generally had a positive attitude towards nudges, especially when they were aligned with product preferences, information needs, and beliefs about the food environment. Still, some interviewees also expressed distrust towards nudging strategies, suspecting ulterior motives. We conclude that nudging strategies should target foods which align with product preferences and information needs. However, the suspicion of ulterior motives highlights an important concern which should be considered when implementing supermarket-based nudging strategies.
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http://dx.doi.org/10.3390/ijerph18116175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201246PMC
June 2021

Residential exposure to fast-food restaurants and its association with diet quality, overweight and obesity in the Netherlands: a cross-sectional analysis in the EPIC-NL cohort.

Nutr J 2021 06 16;20(1):56. Epub 2021 Jun 16.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Background: Unhealthy food environments may contribute to unhealthy diets and risk of overweight and obesity through increased consumption of fast-food. Therefore, we aimed to study the association of relative exposure to fast-food restaurants (FFR) with overall diet quality and risk of overweight and obesity in a sample of older adults.

Methods: We analyzed cross-sectional data of the EPIC-NL cohort (n = 8,231). Data on relative FFR exposure was obtained through linkage of home address in 2015 with a retail outlet database. We calculated relative exposure to FFR by dividing the densities of FFR in street-network buffers of 400, 1000, and 1500 m around the home of residence by the density of all food retailers in the corresponding buffer. We calculated scores on the Dutch Healthy Diet 2015 (DHD15) index using data from a validated food-frequency questionnaire. BMI was categorized into normal weight (BMI < 25), overweight (25 ≤ BMI < 30), and obesity (BMI ≥ 30). We used multivariable linear regression (DHD15-index) and multinomial logistic regression (weight status), using quartiles of relative FFR exposure as independent variable, adjusting for lifestyle and environmental characteristics.

Results: Relative FFR exposure was not significantly associated with DHD15-index scores in the 400, 1000, and 1500 m buffers (β= -0.21 [95 %CI: -1.12; 0.70]; β= -0.12 [95 %CI: -1.10; 0.87]; β = 0.37 [95 %CI: -0.67; 1.42], respectively). Relative FFR exposure was also not related to overweight in consecutive buffers (OR=1.10 [95 %CI: 0.97; 1.25]; OR=0.97 [95 %CI: 0.84; 1.11]; OR= 1.04 [95 %CI: 0.90-1.20]); estimates for obesity were similar to those of overweight.

Conclusions: A high proportion of FFR around the home of residence was not associated with diet quality or overweight and obesity in this large Dutch cohort of older adults. We conclude that although the food environment may be a determinant of food choice, this may not directly translate into effects on diet quality and weight status. Methodological improvements are warranted to provide more conclusive evidence.
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http://dx.doi.org/10.1186/s12937-021-00713-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210363PMC
June 2021

Associations between dietary amino acid intakes and blood concentration levels.

Clin Nutr 2021 Jun 27;40(6):3772-3779. Epub 2021 Apr 27.

International Agency for Research on Cancer, Nutrition and Metabolism Section, 69372, Lyon CEDEX 08, France.

Background And Aims: Emerging evidence suggests a role of amino acids (AAs) in the development of various diseases including renal failure, liver cirrhosis, diabetes and cancer. However, mechanistic pathways and the effects of dietary AA intakes on circulating levels and disease outcomes are unclear. We aimed to compare protein and AA intakes, with their respective blood concentrations in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: Dietary protein and AA intakes were assessed via the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR). A subsample of 3768 EPIC participants who were free of cancer had blood AA concentrations measured. To investigate how circulating levels relate to their respective intakes, dietary AA intake was examined in quintiles and ANOVA tests were run. Pearson correlations were examined for continous associations between intakes and blood concentrations.

Results: Dietary AA intakes (assessed with the DQ) and blood AA concentrations were not strongly correlated (-0.15 ≤ r ≤ 0.17) and the direction of the correlations depended on AA class: weak positive correlations were found for most essential AAs (isoleucine, leucine, lysine, methionine, threonine, tryptophan, and valine) and conditionally essential AAs (arginine and tyrosine), while negative associations were found for non-essential AAs. Similar results were found when using the 24-HDR. When conducting ANOVA tests for essential AAs, higher intake quintiles were linked to higher blood AA concentrations, except for histidine and phenylalanine. For non-essential AAs and glycine, an inverse relationship was observed. Conditionally-essential AAs showed mixed results.

Conclusions: Weak positive correlations and dose responses were found between most essential and conditionally essential AA intakes, and blood concentrations, but not for the non-essential AAs. These results suggest that intake of dietary AA might be related to physiological AA status, particularly for the essential AAs. However, these results should be further evaluated and confirmed in large-scale prospective studies.
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http://dx.doi.org/10.1016/j.clnu.2021.04.036DOI Listing
June 2021

Age at Menopause and Risk of Ischemic and Hemorrhagic Stroke.

Stroke 2021 Aug 3;52(8):2583-2591. Epub 2021 Jun 3.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands (S.J.G.C.W., N.C.O.-M., W.M.M.V., Y.T.v.d.S.).

Background And Purpose: The few epidemiological studies that addressed the association between age at menopause and ischemic and hemorrhagic stroke risk in women had conflicting findings. We aimed to investigate whether age at (natural and surgical) menopause is a risk factor for total, ischemic, and hemorrhagic stroke in women.

Methods: We analyzed data from 16 244 postmenopausal women, aged 26 to 70 years at recruitment who were enrolled in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort between 1993 and 1997. Participants were followed for the occurrence of stroke until January 1, 2011. At baseline, participants filled in questionnaires about health, reproductive history including age at menopause, diet, and lifestyle. Cox regression was used to investigate the association between age at menopause and stroke. All analyses were adjusted for age, smoking, systolic blood pressure, and body mass index.

Results: Mean age of menopause was 46.4 (7.0) years. A total of 830 strokes (571 ischemic, 162 hemorrhagic, 97 unclassified) were identified. Earlier menopause was associated with an increased risk of total stroke. Compared with women who experienced menopause between 50 and 54 years old, women who underwent menopause before age 40 years had 1.48× higher risk (95% CI, 1.19-1.85) of total stroke. In continuous analyses, we observed a 2% lower total stroke risk for each year menopause was delayed (hazard ratio, 0.98 [95% CI, 0.97-0.99]). The risk between earlier menopause and stroke was confined to ischemic stroke, earlier menopause was not associated with hemorrhagic stroke. The association with age at menopause was stronger for natural menopause (hazard ratio <40 versus 50-54 years, 1.74 [95% CI, 1.12-2.70]) than for surgical menopause (hazard ratio <40 versus 50-54 years, 1.26 [95% CI, 0.84-1.89]).

Conclusions: The risk of total and ischemic stroke decreased with an increase in age at menopause. Whether this should have clinical consequences such as intensified risk factor control should be subject of further studies.
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http://dx.doi.org/10.1161/STROKEAHA.120.030558DOI Listing
August 2021

Long-Term Exposure to Fine Particle Elemental Components and Natural and Cause-Specific Mortality-a Pooled Analysis of Eight European Cohorts within the ELAPSE Project.

Environ Health Perspect 2021 Apr 12;129(4):47009. Epub 2021 Apr 12.

Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Background: Inconsistent associations between long-term exposure to particles with an aerodynamic diameter [fine particulate matter ()] components and mortality have been reported, partly related to challenges in exposure assessment.

Objectives: We investigated the associations between long-term exposure to elemental components and mortality in a large pooled European cohort; to compare health effects of components estimated with two exposure modeling approaches, namely, supervised linear regression (SLR) and random forest (RF) algorithms.

Methods: We pooled data from eight European cohorts with 323,782 participants, average age 49 y at baseline (1985-2005). Residential exposure to 2010 annual average concentration of eight components [copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V), and zinc (Zn)] was estimated with Europe-wide SLR and RF models at a scale. We applied Cox proportional hazards models to investigate the associations between components and natural and cause-specific mortality. In addition, two-pollutant analyses were conducted by adjusting each component for mass and nitrogen dioxide () separately.

Results: We observed 46,640 natural-cause deaths with 6,317,235 person-years and an average follow-up of 19.5 y. All SLR-modeled components were statistically significantly associated with natural-cause mortality in single-pollutant models with hazard ratios (HRs) from 1.05 to 1.27. Similar HRs were observed for RF-modeled Cu, Fe, K, S, V, and Zn with wider confidence intervals (CIs). HRs for SLR-modeled Ni, S, Si, V, and Zn remained above unity and (almost) significant after adjustment for both and . HRs only remained (almost) significant for RF-modeled K and V in two-pollutant models. The HRs for V were 1.03 (95% CI: 1.02, 1.05) and 1.06 (95% CI: 1.02, 1.10) for SLR- and RF-modeled exposures, respectively, per , adjusting for mass. Associations with cause-specific mortality were less consistent in two-pollutant models.

Conclusion: Long-term exposure to V in was most consistently associated with increased mortality. Associations for the other components were weaker for exposure modeled with RF than SLR in two-pollutant models. https://doi.org/10.1289/EHP8368.
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http://dx.doi.org/10.1289/EHP8368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041432PMC
April 2021

An elevated ankle-brachial index is not a valid proxy for peripheral medial arterial calcification.

Atherosclerosis 2021 04 13;323:13-19. Epub 2021 Mar 13.

Amsterdam UMC, location VUmc, Department of Epidemiology & Data Science, Amsterdam Cardiovascular Sciences, De Boelelaan, 1117, Amsterdam, the Netherlands; University Medical Centre Utrecht, Utrecht University, Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands.

Background And Aims: The ankle brachial index (ABI) is often used as a proxy for medial arterial calcification (MAC) in studies investigating MAC as a cardiovascular risk factor, but evidence supporting this hypothesis is sparse. This study aims to investigate the use of an elevated ABI as proxy for MAC, as visualized with computed tomography (CT).

Methods: Cross-sectional data of 718 participants with, or at risk of cardiovascular disease was used. The ABI was calculated using cutoffs >1.4 and > 1.3. The presence of MAC was assessed in the crural and femoral arteries by CT imaging. Modified Poisson regression was used to assess the association between an elevated ABI and the presence of MAC, and test characteristics were calculated.

Results: MAC was found in 25.0% of participants. An ABI >1.4 was found in 8.7% of participants, of whom 45.2% had MAC. An elevated ABI was significantly associated with the presence of MAC (RR 1.74, CI: 1.26-2.40). However, poor positive specific agreement (23.3%, CI: 13.9-34.3), sensitivity (15.7%, CI: 10.4-21.1) and positive predictive value (45.2%, CI: 32.8-57.5) were found. Despite good specificity (93.6%, CI: 91.6-95.7) the area under the receiving operator curve remained poor (54.7%, CI: 51.8-57.6). Negative specific agreement (84.5%, CI: 81.4-87.0) and negative predictive value (77.0%, CI: 73.7-80.2) were acceptable.

Conclusions: An elevated ABI is insufficient to serve as a true diagnostic proxy for MAC. Studies that have drawn conclusions on the association between MAC and cardiovascular disease, solely based on the ABI, are likely to underestimate the found effects.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.010DOI Listing
April 2021

Substitution of pure fruit juice for fruit and sugar-sweetened beverages and cardiometabolic risk in European Prospective Investigation into Cancer and Nutrition (EPIC)-NL: a prospective cohort study.

Public Health Nutr 2021 Mar 1:1-11. Epub 2021 Mar 1.

Center for Nutrition, Prevention, and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven3720 BA, The Netherlands.

Objective: Dietary guidelines on pure fruit juice differ between countries regarding the question whether pure fruit juice (without added sugars) is an acceptable substitute for fruit or should be avoided because of its comparable sugar content with that of sugar-sweetened beverages (SSB). We modelled whether substituting pure fruit juice for fruit or SSB was associated with cardiometabolic risk.

Design: Prospective cohort study.

Setting: Based on a validated FFQ at baseline, we calculated the relative contribution of pure fruit juice to total consumption of fruit and pure fruit juice (${{{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\;\left( {{\rm{g}}/{\rm{day}}} \right)} \over {{\rm{fruit}}\; + \;{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\left( {{\rm{g}}/{\rm{day}}} \right)}}$) and to total consumption of SSB and pure fruit juice (${{{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\;\left( {{\rm{g}}/{\rm{day}}} \right)} \over {{\rm{SSBs}}\; + \;{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\left( {{\rm{g}}/{\rm{day}}} \right)}}$). In multivariate analyses (Cox regression), we assessed associations with incidence of type 2 diabetes, CVD, CHD and stroke after an average follow-up of 14·6 years.

Participants: About 35 000 participants from the EPIC-NL study, aged 20-70 years at enrolment.

Results: Substitution of pure fruit juice for SSB was associated with lower risk of all endpoints. For type 2 diabetes and CHD, for example, drinking 75-100 % (as compared with 0-<25 %) of total SSB + pure fruit juice as pure fruit juice showed hazard ratio (95 % CI) of 0·74 (95 % CI 0·64, 0·85) and 0·85 (95 % CI 0·76, 0·96), respectively. Substitution of pure fruit juice for fruit was not associated with the risk of type 2 diabetes, CVD, CHD and stroke.

Conclusions: Substituting pure fruit juice for SSB was associated with lower cardiometabolic risk, whereas substituting pure fruit juice for fruit was not associated with cardiometabolic risk.
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http://dx.doi.org/10.1017/S1368980021000914DOI Listing
March 2021

Anti-Müllerian Hormone Levels and Risk of Cancer in Women.

Maturitas 2021 Jan 2;143:216-222. Epub 2020 Nov 2.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address:

Objectives: To examine if age-specific anti-Müllerian hormone (AMH) levels are associated with cancer risk; and to investigate if age-related AMH trajectories differ between women who develop cancer and women who do not. More specifically, we examined associations with breast cancer, cancers in other tissues expressing AMH receptor AMHR2, and cancers in non-AMHR2-expressing tissues.

Study Design: We included longitudinal data from 3025 women in the prospective Doetinchem Cohort Study. Cox proportional hazards models were used to assess the association of baseline age-specific AMH tertiles with cancer. We applied linear mixed models to compare age-related AMH trajectories between women who were diagnosed with cancer and women who were not.

Main Outcome Measures: Cancer (n = 385; 139 breast cancers, 112 cancers in other AMHR2-expressing tissues, 134 cancers in non-AMHR2-expressing tissues).

Results: Overall, baseline age-specific AMH levels were not associated with cancer risk, although in women ≤ 40 years an increased risk was suggested for breast cancer (HR = 2.06, 95%CI = 0.95-4.48; HR = 2.03, 95%CI = 0.91-4.50). Analysis of age-related AMH trajectories suggested that AMH levels were higher at younger ages and declined faster in women who were diagnosed with cancer compared with women who were not, but our results did not provide evidence for actual differences in trajectories.

Conclusions: Our results did not provide evidence for an association between age-specific AMH levels and age-related trajectories and risk of cancer. However, effect estimates for breast cancer were in line with risk-increasing effects found in previous studies.
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http://dx.doi.org/10.1016/j.maturitas.2020.10.017DOI Listing
January 2021

Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.

Diabetes Care 2021 Jan 17;44(1):98-106. Epub 2020 Nov 17.

Unit of Nutrition and Cancer, Cancer Epidemiology Research Program and Translational Research Laboratory; Catalan Institute of Oncology - ICO, Group of Research on Nutrition and Cancer, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet of Llobregat, Barcelona, Spain.

Objective: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

Research Design And Methods: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.

Results: We identified 11 genomic regions associated with plasma vitamin C ( < 5 × 10), with the strongest signal at , and 10 novel genetic loci including , , , , , , , , , and . Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

Conclusions: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
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http://dx.doi.org/10.2337/dc20-1328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783939PMC
January 2021

Early Onset of Coronary Artery Calcification in Women With Previous Preeclampsia.

Circ Cardiovasc Imaging 2020 11 16;13(11):e010340. Epub 2020 Nov 16.

Department of Internal Medicine (J.E.R.v.L.), University Medical Center Rotterdam, the Netherlands.

Background: Preeclampsia, coronary artery calcification (CAC), and atherosclerotic plaque are risk factors for the development of cardiovascular disease. We determined at what age CAC becomes apparent on coronary computed tomography after preeclampsia and to what extent modifiable cardiovascular risk factors were associated.

Methods: We measured cardiovascular risk factors, CAC by coronary computed tomography, and coronary plaque by coronary computed tomography angiography in 258 previously preeclamptic women aged 40-63. Results were compared to 644 age- and ethnicity-equivalent women from the Framingham Heart Study with previous normotensive pregnancies.

Results: Any CAC was more prevalent after preeclampsia than after a normotensive pregnancy (20% versus 13%). However, this difference was greatest and statistically significant only in women ages 45 to 50 (23% versus 10%). The degree of CAC advanced 4× faster between the ages of 40 to 45 and ages 45 to 50 in women with a history of preeclampsia (odds ratio, 4.3 [95% CI, 1.5-12.2] versus odds ratio, 1.2 [95% CI, 0.6-2.3]). Women with a preeclampsia history maintained greater advancement of CAC with age into their early 60s, although this difference declined after the perimenopausal years. Women with a previous normotensive pregnancy were 4.9 years (95% CI, 1.8-8.0) older when they had similar CAC scores as previously preeclamptic women. These observations were not explained by the greater prevalence of cardiovascular disease risk factors, and the higher Framingham Risk Scores also observed in women with a history of preeclampsia.

Conclusions: Previously preeclamptic women have more modifiable cardiovascular risk factors and develop CAC ≈5 years earlier from the age of 45 years onwards compared to women with normotensive pregnancies. Therefore, women who experienced preeclampsia might benefit from regular cardiovascular screening and intervention before this age. Registration: URL: https://www.trialregister.nl/trial/5406; Unique identifier: NTR5531.
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http://dx.doi.org/10.1161/CIRCIMAGING.119.010340DOI Listing
November 2020

Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study.

Sci Data 2020 11 13;7(1):393. Epub 2020 Nov 13.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Type 2 diabetes (T2D) is a global public health challenge. Whilst the advent of genome-wide association studies has identified >400 genetic variants associated with T2D, our understanding of its biological mechanisms and translational insights is still limited. The EPIC-InterAct project, centred in 8 countries in the European Prospective Investigations into Cancer and Nutrition study, is one of the largest prospective studies of T2D. Established as a nested case-cohort study to investigate the interplay between genetic and lifestyle behavioural factors on the risk of T2D, a total of 12,403 individuals were identified as incident T2D cases, and a representative sub-cohort of 16,154 individuals was selected from a larger cohort of 340,234 participants with a follow-up time of 3.99 million person-years. We describe the results from a genome-wide association analysis between more than 8.9 million SNPs and T2D risk among 22,326 individuals (9,978 cases and 12,348 non-cases) from the EPIC-InterAct study. The summary statistics to be shared provide a valuable resource to facilitate further investigations into the genetics of T2D.
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http://dx.doi.org/10.1038/s41597-020-00716-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666191PMC
November 2020

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women.

medRxiv 2020 Nov 3. Epub 2020 Nov 3.

Anti-Müllerian hormone (AMH) is expressed by antral stage ovarian follicles in women. Consequently, circulating AMH levels are detectable until menopause. Variation in age-specific AMH levels has been associated with breast cancer and polycystic ovary syndrome (PCOS), amongst other diseases. Identification of genetic variants underlying variation in AMH levels could provide clues about the physiological mechanisms that explain these AMH-disease associations. To date, only one variant in has been identified to be associated with circulating AMH levels in women. We aimed to identify additional variants for AMH through a GWAS meta-analysis including data from 7049 premenopausal women of European ancestry, which more than doubles the sample size of the largest previous GWAS. We identified four loci associated with AMH levels at p < 5×10 : the previously reported locus and three novel signals in or near , and . The strongest signal was a missense variant in the gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among SNPs for AMH levels and for age at menopause (r = 0.82, FDR=0.003). Exploratory Mendelian randomization analyses did not support a causal effect of AMH on breast cancer or PCOS risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored. In conclusion, we identified a variant in the gene and three other loci that may affect circulating AMH levels in women.
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http://dx.doi.org/10.1101/2020.10.29.20221390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654897PMC
November 2020

The association of the Mediterranean diet with heart failure risk in a Dutch population.

Nutr Metab Cardiovasc Dis 2021 01 12;31(1):60-66. Epub 2020 Aug 12.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Background And Aims: It is still unclear whether a healthy diet can prevent heart failure (HF). Therefore, this study aimed to investigate the association between adherence to a Mediterranean-style diet, reflected by modified Mediterranean Diet Scores (mMDS), and the incidence of HF in men and women.

Methods And Results: This observational study comprised 9316 men and 27,645 women from the EPIC-NL cohort free from cardiovascular disease at baseline. Dietary intakes were assessed using a validated food frequency questionnaire. mMDS was calculated using a 9-point scale based on consumption of vegetables, legumes, fruit, nuts, seeds, grains, fish, fat ratio, dairy, meat and alcohol. HF events were ascertained by linkage to nation-wide registries. Multivariable Hazard Ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards regression models. Over a median follow-up of 15 years (IQR 14-16), 633 HF events occurred: 144 in men (1.5%) and 489 in women (1.8%). The median mMDS was 4 (IQR 3-5). There was significant effect modification by sex (P-value for interaction <0.001), therefore results are stratified for men and women. For men, a higher mMDS associated with lower HF risk (HR: 0.88; 95% CI: 0.79, 0.98 per point increase in mMDS; HR upper category: 0.53; 95% CI: 0.33, 0.86), whereas no association was found in women (HR: 0.98; 95% CI: 0.93, 1.04 per point increase; HR upper category: 1.07; 95% CI: 0.83, 1.36).

Conclusion: Adherence to a Mediterranean-style diet may reduce HF risk, particularly in men. The underlying reasons for the differences in findings between men and women need further study.
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http://dx.doi.org/10.1016/j.numecd.2020.08.003DOI Listing
January 2021

Six months vitamin K treatment does not affect systemic arterial calcification or bone mineral density in diabetes mellitus 2.

Eur J Nutr 2021 Apr 17;60(3):1691-1699. Epub 2020 Oct 17.

Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Location VUmc, Amsterdam Public Health and Amsterdam Cardiovascular Sciences Research Institutes, Postbox 7057, 1007 MB, Amsterdam, The Netherlands.

Purpose: Vitamin K-dependent proteins are involved in (patho)physiological calcification of the vasculature and the bones. Type 2 diabetes mellitus (DM2) is associated with increased arterial calcification and increased fractures. This study investigates the effect of 6 months vitamin K2 supplementation on systemic arterial calcification and bone mineral density (BMD) in DM2 patients with a history of cardiovascular disease (CVD).

Methods: In this pre-specified, post hoc analysis of a double-blind, randomized, controlled clinical trial, patients with DM2 and CVD were randomized to a daily, oral dose of 360 µg vitamin K2 or placebo for 6 months. CT scans were made at baseline and follow-up. Arterial calcification mass was quantified in several large arterial beds and a total arterial calcification mass score was calculated. BMD was assessed in all non-fractured thoracic and lumbar vertebrae.

Results: 68 participants were randomized, 35 to vitamin K2 (33 completed follow-up) and 33 to placebo (27 completed follow-up). The vitamin K group had higher arterial calcification mass at baseline [median (IQR): 1694 (812-3584) vs 1182 (235-2445)] for the total arterial calcification mass). Six months vitamin K supplementation did not reduce arterial calcification progression (β [95% CI]: - 0.02 [- 0.10; 0.06] for the total arterial calcification mass) or slow BMD decline (β [95% CI]: - 2.06 [- 11.26; 7.30] Hounsfield units for all vertebrae) when compared to placebo.

Conclusion: Six months vitamin K supplementation did not halt progression of arterial calcification or decline of BMD in patients with DM2 and CVD. Future clinical trials may want to pre-select patients with very low vitamin K status and longer follow-up time might be warranted. This trial was registered at clinicaltrials.gov as NCT02839044.
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http://dx.doi.org/10.1007/s00394-020-02412-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987615PMC
April 2021

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.

PLoS Med 2020 10 16;17(10):e1003394. Epub 2020 Oct 16.

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis.

Methods And Findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities.

Conclusions: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.
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http://dx.doi.org/10.1371/journal.pmed.1003394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567390PMC
October 2020

Anti-Müllerian hormone levels and risk of type 2 diabetes in women.

Diabetologia 2021 Feb 13;64(2):375-384. Epub 2020 Oct 13.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Aims/hypothesis: Given its role in ovarian follicle development, circulating anti-Müllerian hormone (AMH) is considered to be a marker of reproductive ageing. Although accelerated reproductive ageing has been associated with a higher risk of type 2 diabetes, research on the relationship between AMH and type 2 diabetes risk is scarce. Therefore, we aimed to investigate whether age-specific AMH levels and age-related AMH trajectories are associated with type 2 diabetes risk in women.

Methods: We measured AMH in repeated plasma samples from 3293 female participants (12,460 samples in total), aged 20-59 years at recruitment, from the Doetinchem Cohort Study, a longitudinal study with follow-up visits every 5 years. We calculated age-specific AMH tertiles at baseline to account for the strong AMH-age correlation. Cox proportional hazards models adjusted for confounders were used to assess the association between baseline age-specific AMH tertiles and incident type 2 diabetes. We applied linear mixed models to compare age-related AMH trajectories for women who developed type 2 diabetes with trajectories for women who did not develop diabetes.

Results: During a median follow-up of 20 years, 163 women developed type 2 diabetes. Lower baseline age-specific AMH levels were associated with a higher type 2 diabetes risk (HR 1.24 [95% CI 0.81, 1.92]; HR 1.62 [95% CI 1.06, 2.48]; p = 0.02). These findings seem to be supported by predicted AMH trajectories, which suggested that plasma AMH levels were lower at younger ages in women who developed type 2 diabetes compared with women who did not. The trajectories also suggested that AMH levels declined at a slower rate in women who developed type 2 diabetes, although differences in trajectories were not statistically significant.

Conclusions/interpretation: We observed that lower age-specific AMH levels were associated with a higher risk of type 2 diabetes in women. Longitudinal analyses did not show clear evidence of differing AMH trajectories between women who developed type 2 diabetes compared with women who did not, possibly because these analyses were underpowered. Further research is needed to investigate whether AMH is part of the biological mechanism explaining the association between reproductive ageing and type 2 diabetes. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05302-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801305PMC
February 2021

The effects of nudges on purchases, food choice, and energy intake or content of purchases in real-life food purchasing environments: a systematic review and evidence synthesis.

Nutr J 2020 09 17;19(1):103. Epub 2020 Sep 17.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, P.O. box 85500, 3508 GA, Utrecht, The Netherlands.

Background: Adults with a low socioeconomic position (SEP) are more likely to engage in unhealthy diets as compared to adults with high SEP. However, individual-level educational interventions aiming to improve food choices have shown limited effectiveness in adults with low SEP. Environmental-level interventions such as nudging strategies however, may be more likely to benefit low SEP groups. We aimed to review the evidence for the effectiveness of nudges as classified according to interventions in proximal physical micro-environments typology (TIPPME) to promote healthy purchases, food choice, or affecting energy intake or content of purchases, within real-life food purchasing environments. Second, we aimed to investigate the potentially moderating role of SEP.

Methods: We systematically searched PubMed, EMBASE, and PsycINFO until 31 January 2018. Studies were considered eligible for inclusion when they i) complied with TIPPME intervention definitions; ii) studied actual purchases, food choice, or energy intake or content of purchases, iii) and were situated in real-life food purchasing environments. Risk of bias was assessed using a quality assessment tool and evidence was synthesized using harvest plots.

Results: From the 9210 references identified, 75 studies were included. Studies were generally of weak to moderate quality. The most frequently studied nudges were information (56%), mixed (24%), and position nudges (13%). Harvest plots showed modest tendencies towards beneficial effects on outcomes for information and position nudges. Less evidence was available for other TIPPME nudging interventions for which the harvest plots did not show compelling patterns. Only six studies evaluated the effects of nudges across levels of SEP (e.g., educational level, food security status, job type). Although there were some indications that nudges were more effective in low SEP groups, the limited amount of evidence and different proxies of SEP used warrant caution in the interpretation of findings.

Conclusions: Information and position nudges may contribute to improving population dietary behaviours. Evidence investigating the moderating role of SEP was limited, although some studies reported greater effects in low SEP subgroups. We conclude that more high-quality studies obtaining detailed data on participant's SEP are needed.

Registration: This systematic review is registered in the PROSPERO database ( CRD42018086983 ).
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http://dx.doi.org/10.1186/s12937-020-00623-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500553PMC
September 2020

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

BMJ 2020 09 16;370:m3173. Epub 2020 Sep 16.

AOU Federico II, Naples, Italy.

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.
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http://dx.doi.org/10.1136/bmj.m3173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491938PMC
September 2020

Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations: The EPIC-InterAct Study.

Diabetes Care 2020 11 31;43(11):2660-2667. Epub 2020 Aug 31.

CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Objective: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact.

Research Design And Methods: The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis.

Results: There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat (50 g/day) with cheese (HR 0.90, 95% CI 0.83-0.97) (30 g/day), yogurt (0.90, 0.86-0.95) (70 g/day), nuts (0.90, 0.84-0.96) (10 g/day), or cereals (0.92, 0.88-0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes.

Conclusions: Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.
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http://dx.doi.org/10.2337/dc20-1038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576430PMC
November 2020

To what extent do dietary costs explain socio-economic differences in dietary behavior?

Nutr J 2020 08 24;19(1):88. Epub 2020 Aug 24.

Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan, 1117, Amsterdam, the Netherlands.

Background: Low socio-economic position is associated with consumption of lower quality diets, which may be partly explained by the cost of healthier diets. Therefore, we aimed to investigate the mediating role of dietary costs in the association between educational level and diet quality.

Methods: We used cross-sectional data from Dutch older adults (N = 9399) in the EPIC-NL cohort. Participants provided information about their own and their partners' highest attained educational level (as proxy for socio-economic position). Dietary behavior was assessed using a food frequency questionnaire from which we derived two diet-quality scores, including the Dutch Healthy Diet index 2015 (DHD15-index) and the Dietary Approaches to Stop Hypertension (DASH) diet. Dietary cost estimates were based on food price data from food stores, and linked to reported consumption of food items. Multiple regression analyses and bootstrapping were used examine the mediating role of dietary cost in the association between educational level and diet quality.

Results: Mean age of participants was 70 (SD: 10) years and 77% were women. Dietary costs significantly mediated the association between educational level and diet quality, except for high versus middle individual educational level and the DHD15-index. Depending on the dietary and educational indicator, dietary costs explained between 2 and 7% of the association between educational level and diet quality. Furthermore, associations were found to be modified by sex and age. For the DHD15-index, mediation effects were only present in females and adults older than 65 years, and for the DASH diet mediation effects were only present in females and strongest amongst adults older than 65 years compared to adults younger than 65 years.

Conclusion: Dietary costs seems to play a modest role in explaining educational differences in diet quality in an older Dutch population. Further research is needed to investigate which other factors may explain SEP differences in diet quality.
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http://dx.doi.org/10.1186/s12937-020-00608-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446174PMC
August 2020

Intimal and medial calcification in relation to cardiovascular risk factors.

PLoS One 2020 13;15(7):e0235228. Epub 2020 Jul 13.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Purpose: To assess specific risk factors and biomarkers associated with intimal arterial calcification (IAC) and medial arterial calcification (MAC).

Methods: We conducted a cross-sectional study in patients with or at risk of vascular disease from the SMART study(n = 520) and the DCS cohort(n = 198). Non-contrast computed tomography scanning of the lower extremities was performed and calcification in the femoral and crural arteries was scored as absent, predominant IAC, predominant MAC or indistinguishable. Multinomial regression models were used to assess the associations between cardiovascular risk factors and calcification patterns. Biomarkers for inflammation, calcification and vitamin K status were measured in a subset of patients with IAC(n = 151) and MAC(n = 151).

Results: Femoral calcification was found in 77% of the participants, of whom 38% had IAC, 28% had MAC and 11% were scored as indistinguishable. The absolute agreement between the femoral and crural arteries was high(69%). Higher age, male sex, statin use and history of coronary artery disease were associated with higher prevalences of femoral IAC and MAC compared to absence of calcification. Smoking and low ankle-brachial-index (ABI) were associated with higher prevalence of IAC and high ABI was associated with less IAC. Compared to patients with IAC, patients with MAC more often had diabetes, have a high ABI and were less often smokers. Inactive Matrix-Gla Protein was associated with increased MAC prevalence, while osteonectin was associated with decreased risk of MAC, compared to IAC.

Conclusions: When femoral calcification is present, the majority of the patients have IAC or MAC throughout the lower extremity, which have different associated risk factor profiles.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235228PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357737PMC
September 2020

Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries.

BMJ 2020 07 8;370:m2194. Epub 2020 Jul 8.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.

Design: Prospective case-cohort study.

Setting: Populations from eight European countries.

Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.

Main Outcome Measure: Incident type 2 diabetes.

Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.

Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
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http://dx.doi.org/10.1136/bmj.m2194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341350PMC
July 2020

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

Am J Clin Nutr 2020 09;112(3):631-643

Center for Research in Epidemiology and Population Health, University Paris-South, Faculty of Medicine, University Versailles-St Quentin, National Institute for Health and Medical Research, Université Paris-Saclay, Villejuif, France.

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.
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http://dx.doi.org/10.1093/ajcn/nqaa157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458777PMC
September 2020

Proactive screening for symptoms: A simple method to improve early detection of unrecognized cardiovascular disease in primary care. Results from the Lifelines Cohort Study.

Prev Med 2020 09 27;138:106143. Epub 2020 May 27.

University Medical Center Groningen, University of Groningen, Department of Cardiology, Groningen, the Netherlands. Electronic address:

Cardiovascular disease (CVD) often goes unrecognized, despite symptoms frequently being present. Proactive screening for symptoms might improve early recognition and prevent disease progression or acute cardiovascular events. We studied the diagnostic value of symptoms for the detection of unrecognized atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) and developed a corresponding screening questionnaire. We included 100,311 participants (mean age 52 ± 9 years, 58% women) from the population-based Lifelines Cohort Study. For each outcome (unrecognized AF/HF/CAD), we built a multivariable model containing demographics and symptoms. These models were combined into one 'three-disease' diagnostic model and questionnaire for all three outcomes. Results were validated in Lifelines participants with chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM). Unrecognized CVD was identified in 1325 participants (1.3%): AF in 131 (0.1%), HF in 599 (0.6%), and CAD in 687 (0.7%). Added to age, sex, and body mass index, palpitations were independent predictors for unrecognized AF; palpitations, chest pain, dyspnea, exercise intolerance, health-related stress, and self-expected health worsening for unrecognized HF; smoking, chest pain, exercise intolerance, and claudication for unrecognized CAD. Area under the curve for the combined diagnostic model was 0.752 (95% CI 0.737-0.766) in the total population and 0.757 (95% CI 0.734-0.781) in participants with COPD and DM. At the chosen threshold, the questionnaire had low specificity, but high sensitivity. In conclusion, a short questionnaire about demographics and symptoms can improve early detection of CVD and help pre-select people who should or should not undergo further screening for CVD.
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http://dx.doi.org/10.1016/j.ypmed.2020.106143DOI Listing
September 2020

Reducing cardiometabolic risk in adults with a low socioeconomic position: protocol of the Supreme Nudge parallel cluster-randomised controlled supermarket trial.

Nutr J 2020 05 19;19(1):46. Epub 2020 May 19.

Department of Epidemiology and Biostatistics, Amsterdam Public Health research institute, Amsterdam UMC, VU University Amsterdam, Amsterdam, the Netherlands.

Background: Unhealthy lifestyle behaviours such as unhealthy dietary intake and insufficient physical activity (PA) tend to cluster in adults with a low socioeconomic position (SEP), putting them at high cardiometabolic disease risk. Educational approaches aiming to improve lifestyle behaviours show limited effect in this population. Using environmental and context-specific interventions may create opportunities for sustainable behaviour change. In this study protocol, we describe the design of a real-life supermarket trial combining nudging, pricing and a mobile PA app with the aim to improve lifestyle behaviours and lower cardiometabolic disease risk in adults with a low SEP.

Methods: The Supreme Nudge trial includes nudging and pricing strategies cluster-randomised on the supermarket level, with: i) control group receiving no intervention; ii) group 1 receiving healthy food nudges (e.g., product placement or promotion); iii) group 2 receiving nudges and pricing strategies (taxing of unhealthy foods and subsidizing healthy foods). In collaboration with a Dutch supermarket chain we will select nine stores located in low SEP neighbourhoods, with the nearest competitor store at > 1 km distance and managed by a committed store manager. Across the clusters, a personalized mobile coaching app targeting walking behaviour will be randomised at the individual level, with: i) control group; ii) a group receiving the mobile PA app. All participants (target n = 1485) should be Dutch-speaking, aged 45-75 years with a low SEP and purchase more than half of their household grocery shopping at the selected supermarkets. Participants will be recruited via advertisements and mail-invitations followed by community-outreach methods. Primary outcomes are changes in systolic blood pressure, LDL-cholesterol, HbA1c and dietary intake after 12 months follow-up. Secondary outcomes are changes in diastolic blood pressure, blood lipid markers, waist circumference, steps per day, and behavioural factors including healthy food purchasing, food decision style, social cognitive factors related to nudges and to walking behaviours and customer satisfaction after 12 months follow-up. The trial will be reflexively monitored to support current and future implementation.

Discussion: The findings can guide future research and public health policies on reducing lifestyle-related health inequalities, and contribute to a supermarket-based health promotion intervention implementation roadmap.

Trial Registration: Dutch Trial Register ID NL7064, 30th of May, 2018.
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http://dx.doi.org/10.1186/s12937-020-00562-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236937PMC
May 2020

Anti-Müllerian hormone levels and risk of cancer: A systematic review.

Maturitas 2020 May 9;135:53-67. Epub 2020 Mar 9.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands. Electronic address:

Experimental research suggests that anti-Müllerian hormone (AMH) inhibits tumor growth. Conversely, epidemiological studies suggest that higher AMH concentrations increase breast cancer risk, while associations with other cancers are inconsistent. Therefore, our aim was to provide a systematic review of current epidemiological evidence on AMH levels in relation to different cancer types. We performed a systematic search of PubMed and Embase for publications on circulating AMH in relation to cancer. Methodological quality of articles was assessed using the Study Quality Assessment Tools of the National Heart, Lung and Blood Institute. We included 12 articles on breast, ovarian and endometrial cancer, lymphomas, non-gynaecological cancers, childhood cancer and prostate cancer. Five studies measured AMH prior to cancer diagnosis; the other studies measured AMH after diagnosis but prior to treatment. Higher prediagnosis AMH levels were associated with an increased risk of breast cancer. Associations with other types of cancer remained inconclusive, although analyses stratified by age hinted at an increased risk of ovarian and endometrial cancer in younger women. Pretreatment AMH levels were lower in women diagnosed with different types of cancer compared with AMH levels in healthy women. However, because we considered most of the studies that established pretreatment AMH levels to be of poor methodological quality, mainly because of inadequate correction for age at measurement and other important confounders, we refrain from definite conclusions based on these results. Future studies with young participants are needed to assess whether and how AMH affects the risk of different cancer types over time.
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http://dx.doi.org/10.1016/j.maturitas.2020.03.002DOI Listing
May 2020

Consumption of a diet high in dairy leads to higher 15:0 in cholesteryl esters of healthy people when compared to diets high in meat and grain.

Nutr Metab Cardiovasc Dis 2020 05 25;30(5):804-809. Epub 2020 Jan 25.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address:

Background And Aims: A higher dairy product intake has been associated to higher blood concentrations of 15:0 (pentadecanoic acid), 17:0 (margaric acid), and 14:0 (myristic acid). This study investigates whether a diet high in dairy products influences cholesteryl ester fatty acid concentrations of these specific fatty acids (FA).

Methods And Results: In a randomized multiple cross-over study, 13 men and 17 women aged 22 ± 4 years with a BMI of 21.6 ± 2.2 kg/m received 3 isocaloric intervention diets (dairy, meat or grain) in random order. For this post-hoc analysis, FA in plasma cholesteryl esters were measured using gas chromatography. We performed a linear mixed model per centered log-ratio transformed FA, adjusting for period, and the interaction between diet and period. Consumed total fat intake per controlled intervention diet was 31.0 ± 0.9 en%/day (dairy), 31.5 ± 0.6 en%/day (meat), and 28.4 ± 1.2 en%/day (grain), respectively. The dairy diet led to higher relative concentrations of 15:0 when compared to diets high in meat and grain, (β; 0.27, 95%CI: 0.18,0.37; p = 1.2 × 10, and β: 0.15; 95%CI: 0.06,0.24; p = 1.2 × 10, respectively). The dairy diet also led to higher 14:0 when compared to the meat diet (β: 0.34; 95%CI: 0.21,0.46; p = 6.0 × 10), but not when compared to the grain diet. 17:0 did not differ between diets.

Conclusion: The plasma cholesteryl ester fraction after a diet high in dairy was characterized by higher 15:0 levels. Concentrations of 14:0 were only higher when comparing the FA profile after a diet high in dairy when compared to a diet high in meat.

Clinical Trial Registration: ClinicalTrials.gov, NCT01314040.
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http://dx.doi.org/10.1016/j.numecd.2020.01.006DOI Listing
May 2020

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.

Am J Hum Genet 2020 03 27;106(3):389-404. Epub 2020 Feb 27.

Department of Cardiovascular Sciences, University of Leicester, LE3 9QP, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom.

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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http://dx.doi.org/10.1016/j.ajhg.2020.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058826PMC
March 2020

Pure Fruit Juice and Fruit Consumption Are Not Associated with Incidence of Type 2 Diabetes after Adjustment for Overall Dietary Quality in the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) Study.

J Nutr 2020 06;150(6):1470-1477

Center for Nutrition, Prevention, and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.

Background: Dietary guidelines on pure fruit juice consumption vary from country to country regarding the inclusion of pure fruit juice in the recommendations as an acceptable alternative for fruit. Current epidemiological evidence on the association between pure fruit juice consumption and diabetes risk is scarce.

Objective: We studied the association of both pure fruit juice and fruit consumption with diabetes risk and investigated the differences between low and high fruit consumers in the association of pure fruit juice consumption with diabetes risk.

Methods: This prospective cohort study included 36,147 participants in the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) Study aged 20-69 y at baseline. Fruit juice and fruit consumption were assessed using a validated food-frequency questionnaire; amounts of consumption were divided into 5 categories and quintiles, respectively. Incident type 2 diabetes cases were mainly self-reported and verified against medical records. Cox regression was used to estimate adjusted HRs and 95% CIs.

Results: After an average follow-up of 14.6 y, 1477 verified incident cases of type 2 diabetes were documented. Compared with no consumption, pure fruit juice consumption was not significantly associated with type 2 diabetes, with adjusted HRs ranging from 0.92 (95% CI: 0.79, 1.09) to 1.03 (95% CI: 0.83, 1.26). The associations did not differ between participants with low and high fruit consumption. None of the categories of fruit consumption were associated with type 2 diabetes (lowest quintile as reference). Adjusted HRs ranged between 0.93 (95% CI: 0.78, 1.10) and 1.00 (95% CI: 0.84, 1.19). Adjustment for the Dutch Healthy Diet Index, as an overall measure of dietary quality, strongly attenuated the observed associations of type 2 diabetes with both fruit juice and fruit consumption.

Conclusions: We found no evidence for associations between pure fruit juice and fruit consumption and diabetes risk after adjustment for overall dietary quality for participants in the EPIC-NL study. This trial was registered at https://www.trialregister.nl/trial/6939 as NL6939.
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http://dx.doi.org/10.1093/jn/nxz340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269751PMC
June 2020

Adherence to the Dutch dietary guidelines and 15-year incidence of heart failure in the EPIC-NL cohort.

Eur J Nutr 2020 Dec 7;59(8):3405-3413. Epub 2020 Jan 7.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Purpose: A healthy diet may contribute to the primary prevention of heart failure (HF), but evidence is still inconclusive. We aimed to study the association between adherence to the Dutch dietary guidelines and incidence of HF.

Methods: We studied 37,468 participants aged 20-70 years and free of HF at baseline from the EPIC-NL cohort. At baseline (1993-1997), data were collected on demographics, lifestyle, and presence of chronic diseases. Dietary intake was assessed using a 178-item validated food frequency questionnaire. Dietary intake data were used to calculate scores on the Dutch Healthy Diet 2015 Index (DHD15-index) measuring adherence to the Dutch dietary guidelines. The DHD15-index is based on the average daily intake of 14 food groups resulting in a total score ranging between 0 and 140, with higher scores indicating better adherence. HF morbidity and mortality during follow-up were ascertained through linkage with national registries. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between DHD15 adherence and HF risk, adjusting for sociodemographic and lifestyle characteristics.

Results: The average score on the DHD15-index was 71 (SD = 15). During a median follow-up of 15.2 years (IQR 14.1-16.5), 674 HF events occurred. After adjustment for demographic and lifestyle characteristics, higher scores on the DHD15-index were associated with lower risk of HF (HR 0.73; 95% CI 0.58-0.93; P 0.001).

Conclusion: In a large Dutch population of middle-aged adults, higher adherence to the Dutch dietary guidelines was associated with lower risk of HF.
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http://dx.doi.org/10.1007/s00394-019-02170-7DOI Listing
December 2020