Publications by authors named "Joline W J Beulens"

187 Publications

The role of serum and dietary advanced glycation endproducts in relation to cardiac function and structure: The Hoorn Study.

Nutr Metab Cardiovasc Dis 2021 Jul 27. Epub 2021 Jul 27.

Department of Epidemiology & Data Science, Amsterdam UMC-location VUmc, Amsterdam Cardiovascular Sciences Research Institute, Amsterdam, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

Background And Aims: This study aims to investigate the relationship of serum and dietary advanced glycation endproducts (AGEs) with cardiac function and structure after eight years of follow-up.

Methods And Results: We included 370 Hoorn Study participants (aged 66.4 ± 6.1, 47% women). Serum protein-bound AGEs [N-(carboxymethyl)lysine, N-(carboxyethyl)lysine, and pentosidine], as well as echocardiography to assess left atrium volume index (LAVI), left ventricle ejection fraction (LVEF), and left ventricle mass index (LVMI), were measured at baseline and after 8 years of follow-up. Dietary AGEs [N-(carboxymethyl)lysine and N-(carboxyethyl)lysine] were estimated at baseline with a validated food-frequency questionnaire and an AGEs database. Increased pentosidine [-1.4% (-2.6;-0.2)] and overall serum AGEs Z-scores over time [-2.1% (-3.8;-0.5)] were associated with decreased LVEF at follow-up, adjusted for confounders. Glucose metabolism status was an effect modifier (P-for-interaction = 0.04). In participants with impaired glucose metabolism, but not type 2 diabetes, increased pentosidine was associated with decreased LVEF [-4.2 (-8.0;-0.3)%]. Higher dietary N-(carboxyethyl)lysine [1.9 (0.1; 3.7)%] and overall dietary AGEs Z-scores [2.1 (0.1; 4.2)%] were associated with higher LVEF at follow-up. However, prior cardiovascular disease (CVD) was an effect modifier (P = 0.02). We found a stronger, non-significant, association of higher dietary (carboxyethyl)lysine with higher LVEF at follow-up in participants without CVD [2.3 (-0.1; 4.7)%] compared to participants with CVD [0.6 (-2.1; 3.4)%].

Conclusion: Overall serum AGEs were longitudinally associated with impaired systolic function. Future research should focus on including changes in dietary AGEs intake over time and the relation of dietary AGEs with cardiac measures needs to be established in intervention studies using low AGEs diets.
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http://dx.doi.org/10.1016/j.numecd.2021.07.020DOI Listing
July 2021

Impact of taxes on purchases of close substitute foods: analysis of cross-price elasticities using data from a randomized experiment.

Nutr J 2021 Sep 7;20(1):75. Epub 2021 Sep 7.

Department of Public Health, University of Otago, Wellington, New Zealand.

Objective: To examine the effects of health-related food taxes on substitution and complementary purchases within food groups, including from unhealthier to healthier alternatives and between brands.

Methods: We used data from a virtual supermarket experiment with data from 4,259 shopping events linked to varying price sets. Substitution or complementary effects within six frequently purchased food categories were analyzed. Products' own- and cross-price elasticities were analyzed using Almost Ideal Demand System models.

Results: Overall, 37.5% of cross-price elasticities were significant (p < 0.05) and included values greater than 0.10. Supplementary and complementary effects were particularly found in the dairy, meats and snacks categories. For example, a 1% increase in the price of high saturated fat dairy was associated with a 0.18% (SE 0.06%) increase in purchases of low saturated fat dairy. For name- and home-brand products, significant substitution effects were found in 50% (n = 3) of cases, but only in one case this was above the 0.10 threshold.

Conclusions/policy Implications: Given the relatively low own-price elasticities and the limited substitution and complementary effects, relatively high taxes are needed to substantively increase healthy food purchases at the population level.

Trial Registration: This study included secondary analyses; the original trial was registered in the Australian New Zealand Clinical Trials Registry ACTRN12616000122459 .
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http://dx.doi.org/10.1186/s12937-021-00736-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424883PMC
September 2021

Alcohol consumption in relation to cardiovascular diseases and mortality: a systematic review of Mendelian randomization studies.

Eur J Epidemiol 2021 Aug 22. Epub 2021 Aug 22.

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

The causal effects of alcohol-in-moderation on cardiometabolic health are continuously debated. Mendelian randomization (MR) is an established method to address causal questions in observational studies. We performed a systematic review of the current evidence from MR studies on the association between alcohol consumption and cardiometabolic diseases, all-cause mortality and cardiovascular risk factors. We performed a systematic search of the literature, including search terms on type of design and exposure. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. We additionally looked at exploration of non-linearity. We reported the direction of the studied associations. Our search yielded 24 studies that were eligible for inclusion. A full instrumental variable analysis was performed in 17 studies (71%) and 13 out of 24 studies (54%) validated all three key assumptions. Five studies (21%) assessed potential non-linearity. In general, null associations were reported for genetically predicted alcohol consumption with the primary outcomes cardiovascular disease (67%) and diabetes (75%), while the only study on all-cause mortality reported a detrimental association. Considering the heterogeneity in methodological quality of the included MR studies, it is not yet possible to draw conclusions on the causal role of moderate alcohol consumption on cardiometabolic health. As MR is a rapidly evolving field, we expect that future MR studies, especially with recent developments regarding instrument selection and non-linearity methodology, will further substantiate this discussion.
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http://dx.doi.org/10.1007/s10654-021-00799-5DOI Listing
August 2021

Are nudging and pricing strategies on food purchasing behaviors equally effective for all? Secondary analyses from the Supreme Nudge virtual supermarket study.

Appetite 2021 Dec 17;167:105655. Epub 2021 Aug 17.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, De Boelelaan, 1117, Amsterdam, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Nudging and pricing strategies are effective in promoting healthier purchases. However, whether the effects are equal across individuals with different personal characteristics is unknown. This exploratory study aimed to examine differential effects of nudging and pricing strategies on food purchases across individuals' levels of impulsivity, price sensitivity, decision-making styles, and food choice motives. Data from a virtual supermarket experiment where participants were exposed to five study conditions (control, nudging, pricing, salient pricing, and salient pricing with nudging) was used. Participants completed questionnaires assessing their impulsivity, price sensitivity, decision-making styles, and food choice motives. The outcome was the percentage of healthy food purchases. Effect modification was analyzed by adding interaction terms to the statistical models and post-hoc probing was conducted for statistically significant interaction terms. We used data from 400 Dutch adult participants (61.3% female, median age 30.0 years (IQR 24.0)). The effects of the nudging and pricing conditions on healthy food purchases were not modified by impulsivity, price sensitivity, decision-making styles, and the food choice motives 'health' and 'price'. Only the interactions of the food choice motive 'natural content of foods' x pricing (B = -1.02, 90%CI = -2.04; -0.01), the food choice motive 'weight control' x nudging (B = -2.15, 90%CI = -3.34; -0.95), and 'weight control' x pricing (B = -1.87, 90%CI = -3.11; -0.62) were statistically significant. Post-hoc probing indicated that nudging and/or pricing strategies were more effective in individuals who gave lower priority to these food choice motives. The effects of nudging and pricing strategies on increasing healthy food purchasing behaviors, at least in a virtual environment, do not seem to be influenced by personal characteristics and may therefore be implemented as general health promoting strategies.
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http://dx.doi.org/10.1016/j.appet.2021.105655DOI Listing
December 2021

Serum Magnesium Is Inversely Associated With Heart Failure, Atrial Fibrillation, and Microvascular Complications in Type 2 Diabetes.

Diabetes Care 2021 Aug 18;44(8):1757-1765. Epub 2021 Jun 18.

Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands

Objective: We investigated whether serum magnesium (Mg) was prospectively associated with macro- or microvascular complications and mediated by glycemic control (hemoglobin A [HbA]), in type 2 diabetes (T2D).

Research Design And Methods: We analyzed in 4,348 participants the association of serum Mg with macrovascular disease and mortality (acute myocardial infarction [AMI], coronary heart disease [CHD], heart failure [HF], cerebrovascular accident [CVA], and peripheral arterial disease [PAD]), atrial fibrillation (AF), and microvascular complications (chronic kidney disease [CKD], diabetic retinopathy, and diabetic foot) using Cox regression, adjusted for confounders. Mediation analysis was performed to assess whether HbA mediated these associations.

Results: The average baseline serum Mg concentration was 0.80 ± 0.08 mmol/L. During 6.1 years of follow-up, serum Mg was inversely associated with major macrovascular, 0.87 (95% CI 0.76; 1.00); HF, 0.76 (95% CI 0.62; 0.93); and AF, 0.59 (95% CI 0.49; 0.72). Serum Mg was not associated with AMI, CHD, CVA, and PAD. During 5.1 years of follow-up, serum Mg was inversely associated with overall microvascular events, 0.85 (95% CI 0.78; 0.91); 0.89 (95% CI 0.82; 0.96) for CKD, 0.77 (95% CI 0.61; 0.98) for diabetic retinopathy, and 0.85 (95% CI 0.78; 0.92) for diabetic foot. HbA mediated the associations of serum Mg with HF, overall microvascular events, diabetic retinopathy, and diabetic foot.

Conclusions: Serum Mg concentration is inversely associated with the risk to develop HF and AF and with the occurrence of CKD, diabetic retinopathy, and foot complications in T2D. Glycemic control partially mediated the association of serum Mg with HF and microvascular complications.
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http://dx.doi.org/10.2337/dc21-0236DOI Listing
August 2021

The interobserver agreement of ECG abnormalities using Minnesota codes in people with type 2 diabetes.

PLoS One 2021 12;16(8):e0255466. Epub 2021 Aug 12.

Department of Epidemiology and Data Science, Amsterdam University Medical Center, Location VU, Amsterdam, The Netherlands.

Objectives: To assess the interobserver agreement in categories of electrocardiogram (ECG) abnormalities using the Minnesota Code criteria.

Methods: We used a random sample of 180 ECGs from people with type 2 diabetes. ECG abnormalities were classified and coded using the Minnesota ECG Classification. Each ECG was independently rated on several abnormalities by an experienced rater (rater 1) and by two cardiologists (raters 2 and 3) trained to apply the Minnesota codes on four Minnesota codes; 1-codes as an indication for myocardial infarction, 4 en 5-codes as an indication for ischemic abnormalities, 3-codes as an indication for left ventricle hypertrophy, 7-1-codes as an indication for ventricular conduction abnormalities, and 8-3-codes as an indication for atrial fibrillation / atrial flutter. After all pairwise tables were summed, the overall agreement, the specific positive and negative agreement were calculated with a 95% confidence interval (CI) for each abnormality. Also, Kappa's with a 95% CI were calculated.

Results: The overall agreement (with 95% CI) were for myocardial infarction, ischemic abnormalities, left ventricle hypertrophy, conduction abnormalities and atrial fibrillation/atrial flutter respectively: 0.87 (0.84-0.91), 0.79 (0.74-0.84), 0.81 (0.76-0.85), 0.93 (0.90-0.95), 0.96 (0.93-0.97).

Conclusion: This study shows that the overall agreement of the Minnesota code is good to excellent.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255466PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360582PMC
August 2021

Dairy product consumption and incident prediabetes in Dutch middle-aged adults: the Hoorn Studies prospective cohort.

Eur J Nutr 2021 Jul 10. Epub 2021 Jul 10.

Center of Research on Psychological and Somatic Disorders (CORPS), Department of Medical and Clinical Psychology, Tilburg University, PO Box 90153, 5000 LE, Tilburg, The Netherlands.

Purpose: Our aim was to investigate prospective associations of consumption of total dairy and dairy types with incident prediabetes in a Dutch population-based study.

Methods: Two enrolment waves of the Hoorn Studies were harmonized, resulting in an analytic sample of 2262 participants without (pre-) diabetes at enrolment (mean age 56 ± 7.3 years; 50% male). Baseline dietary intake was assessed by validated food frequency questionnaires. Relative risks (RRs) were calculated between dairy, fermented dairy, milk, yogurt (all total/high/low fat), cream and ice cream and prediabetes. Additionally, substituting one serving/day of dairy types associated with prediabetes with alternative dairy types was analysed.

Results: During a mean 6.4 ± 0.7 years of follow-up, 810 participants (35.9%) developed prediabetes. High fat fermented dairy, cheese and high fat cheese were associated with a 17% (RR 0.83, 95% CI 0.69-0.99, p = 0.04), 14% (RR 0.86, 95% CI 0.73-1.02, p = 0.04) and 21% (RR 0.79, 95% CI 0.66-0.94, p = 0.01) lower risk of incident prediabetes, respectively, in top compared to bottom quartiles, after adjustment for confounders. High fat cheese consumption was continuously associated with lower prediabetes risk (RR 0.94, 95% CI 0.88-1.00, p = 0.04). Total dairy and other dairy types were not associated with prediabetes risk in adjusted models, irrespective of fat content (RR ~ 1). Replacing high fat cheese with alternative dairy types was not associated with prediabetes risk.

Conclusion: The highest intake of high fat fermented dairy, cheese and high fat cheese were associated with a lower risk of prediabetes, whereas other dairy types were not associated. Cheese seems to be inversely associated with type 2 diabetes risk, despite high levels of saturated fatty acids and sodium.
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http://dx.doi.org/10.1007/s00394-021-02626-9DOI Listing
July 2021

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

Replication and cross-validation of type 2 diabetes subtypes based on clinical variables: an IMI-RHAPSODY study.

Diabetologia 2021 Sep 10;64(9):1982-1989. Epub 2021 Jun 10.

Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.

Aims/hypothesis: Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes. In the current study we replicate and cross-validate these type 2 diabetes clusters in three large cohorts using variables readily measured in the clinic.

Methods: In three independent cohorts, in total 15,940 individuals were clustered based on age, BMI, HbA, random or fasting C-peptide, and HDL-cholesterol. Clusters were cross-validated against the original clusters based on HOMA measures. In addition, between cohorts, clusters were cross-validated by re-assigning people based on each cohort's cluster centres. Finally, we compared the time to insulin requirement for each cluster.

Results: Five distinct type 2 diabetes clusters were identified and mapped back to the original four All New Diabetics in Scania (ANDIS) clusters. Using C-peptide and HDL-cholesterol instead of HOMA2-B and HOMA2-IR, three of the clusters mapped with high sensitivity (80.6-90.7%) to the previously identified severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) clusters. The previously described ANDIS mild age-related diabetes (MARD) cluster could be mapped to the two milder groups in our study: one characterised by high HDL-cholesterol (mild diabetes with high HDL-cholesterol [MDH] cluster), and the other not having any extreme characteristic (mild diabetes [MD]). When these two milder groups were combined, they mapped well to the previously labelled MARD cluster (sensitivity 79.1%). In the cross-validation between cohorts, particularly the SIDD and MDH clusters cross-validated well, with sensitivities ranging from 73.3% to 97.1%. SIRD and MD showed a lower sensitivity, ranging from 36.1% to 92.3%, where individuals shifted from SIRD to MD and vice versa. People belonging to the SIDD cluster showed the fastest progression towards insulin requirement, while the MDH cluster showed the slowest progression.

Conclusions/interpretation: Clusters based on C-peptide instead of HOMA2 measures resemble those based on HOMA2 measures, especially for SIDD, SIRD and MOD. By adding HDL-cholesterol, the MARD cluster based upon HOMA2 measures resulted in the current clustering into two clusters, with one cluster having high HDL levels. Cross-validation between cohorts showed generally a good resemblance between cohorts. Together, our results show that the clustering based on clinical variables readily measured in the clinic (age, HbA, HDL-cholesterol, BMI and C-peptide) results in informative clusters that are representative of the original ANDIS clusters and stable across cohorts. Adding HDL-cholesterol to the clustering resulted in the identification of a cluster with very slow glycaemic deterioration.
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http://dx.doi.org/10.1007/s00125-021-05490-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382625PMC
September 2021

Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study.

PLoS One 2021 4;16(5):e0251148. Epub 2021 May 4.

Department of Epidemiology & Data Science, Amsterdam UMC, Amsterdam Cardiovascular Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Background: This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex.

Methods: Biomarkers and echocardiographic measures were measured at both baseline and follow-up in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders.

Results: Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %.

Conclusion: Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251148PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096104PMC
May 2021

Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes: Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants.

Nutrients 2021 Apr 7;13(4). Epub 2021 Apr 7.

Postgraduate Program in Epidemiology Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil.

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction ( = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01-1.03, = 61%) for total fish, 1.04 (1.01-1.07, = 46%) for fatty fish, and 1.02 (1.00-1.04, = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02-1.04, = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.
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http://dx.doi.org/10.3390/nu13041223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068031PMC
April 2021

Prognostic models for predicting the risk of foot ulcer or amputation in people with type 2 diabetes: a systematic review and external validation study.

Diabetologia 2021 Jul 27;64(7):1550-1562. Epub 2021 Apr 27.

Department of General Practice, Amsterdam UMC - Location VUmc, Amsterdam Public Health, Amsterdam, the Netherlands.

Aims/hypothesis: Approximately 25% of people with type 2 diabetes experience a foot ulcer and their risk of amputation is 10-20 times higher than that of people without type 2 diabetes. Prognostic models can aid in targeted monitoring but an overview of their performance is lacking. This study aimed to systematically review prognostic models for the risk of foot ulcer or amputation and quantify their predictive performance in an independent cohort.

Methods: A systematic review identified studies developing prognostic models for foot ulcer or amputation over minimal 1 year follow-up applicable to people with type 2 diabetes. After data extraction and risk of bias assessment (both in duplicate), selected models were externally validated in a prospective cohort with a 5 year follow-up in terms of discrimination (C statistics) and calibration (calibration plots).

Results: We identified 21 studies with 34 models predicting polyneuropathy, foot ulcer or amputation. Eleven models were validated in 7624 participants, of whom 485 developed an ulcer and 70 underwent amputation. The models for foot ulcer showed C statistics (95% CI) ranging from 0.54 (0.54, 0.54) to 0.81 (0.75, 0.86) and models for amputation showed C statistics (95% CI) ranging from 0.63 (0.55, 0.71) to 0.86 (0.78, 0.94). Most models underestimated the ulcer or amputation risk in the highest risk quintiles. Three models performed well to predict a combined endpoint of amputation and foot ulcer (C statistics >0.75).

Conclusions/interpretation: Thirty-four prognostic models for the risk of foot ulcer or amputation were identified. Although the performance of the models varied considerably, three models performed well to predict foot ulcer or amputation and may be applicable to clinical practice.
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http://dx.doi.org/10.1007/s00125-021-05448-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075833PMC
July 2021

Shifting toward a healthier dietary pattern through nudging and pricing strategies: A secondary analysis of a randomized virtual supermarket experiment.

Am J Clin Nutr 2021 08;114(2):628-637

Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, VU University Amsterdam, Amsterdam, Netherlands.

Background: Nudging and salient pricing are promising strategies to promote healthy food purchases, but it is possible their effects differ across food groups.

Objective: To investigate in which food groups nudging and/or pricing strategies most effectively changed product purchases and resulted in within-food groups substitutions or spillover effects.

Methods: In total, 318 participants successfully completed a web-based virtual supermarket experiment in the Netherlands. We conducted a secondary analysis of a mixed randomized experiment consisting of 5 conditions (within subject) and 3 arms (between subject) to investigate the single and combined effects of nudging (e.g., making healthy products salient), taxes (25% price increase), and/or subsidies (25% price decrease) across food groups (fruit and vegetables, grains, dairy, protein products, fats, beverages, snacks, and other foods). Generalized linear mixed models were used to estimate the incidence rate ratios and 95% CIs for changes in the number of products purchased.

Results: Compared with the control condition, the combination of subsidies on healthy products and taxes on unhealthy products in the nudging and price salience condition was overall the most effective, as the number of healthy purchases from fruit and vegetables increased by 9% [incidence rate ratio (IRR) = 1.09; 95% CI: 1.02, 1.18], grains by 16% (IRR = 1.16; 95% CI: 1.05, 1.28), and dairy by 58% (IRR = 1.58; 95% CI: 1.31, 1.89), whereas the protein and beverage purchases did not significantly change. Regarding unhealthy purchases, grains decreased by 39% (IRR = 0.72; 95% CI: 0.63, 0.82) and dairy by 30% (IRR = 0.77; 95% CI: 0.68, 0.87), whereas beverage and snack purchases did not significantly change. The groups of grains and dairy showed within-food group substitution patterns toward healthier products. Beneficial spillover effects to minimally targeted food groups were seen for unhealthy proteins (IRR = 0.81; 95% CI: 0.73, 0.91).

Conclusions: Nudging and salient pricing strategies have a differential effect on purchases of a variety of food groups. The largest effects were found for dairy and grains, which may therefore be the most promising food groups to target in order to achieve healthier purchases. The randomized trial on which the current secondary analyses were based is registered in the Dutch trial registry (NTR7293; www.trialregister.nl).
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http://dx.doi.org/10.1093/ajcn/nqab057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326041PMC
August 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

Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions.

J Nutr 2021 05;151(5):1231-1240

School of Public Health, Physiotherapy & Sports Science, University College Dublin, Dublin, Ireland.

Background: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies.

Objective: To examine the prospective associations of total and types of legume intake with the risk of incident T2D.

Methods: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity.

Results: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy.

Conclusions: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.
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http://dx.doi.org/10.1093/jn/nxaa447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112771PMC
May 2021

Performance of Risk Assessment Models for Prevalent or Undiagnosed Type 2 Diabetes Mellitus in a Multi-Ethnic Population-The Helius Study.

Glob Heart 2021 02 12;16(1):13. Epub 2021 Feb 12.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health research institute, Amsterdam, NL.

Background: Most risk assessment models for type 2 diabetes (T2DM) have been developed in Caucasians and Asians; little is known about their performance in other ethnic groups.

Objectives: We aimed to identify existing models for the risk of prevalent or undiagnosed T2DM and externally validate them in a multi-ethnic population currently living in the Netherlands.

Methods: A literature search to identify risk assessment models for prevalent or undiagnosed T2DM was performed in PubMed until December 2017. We validated these models in 4,547 Dutch, 3,035 South Asian Surinamese, 4,119 African Surinamese, 2,326 Ghanaian, 3,598 Turkish, and 3,894 Moroccan origin participants from the HELIUS (Healthy LIfe in an Urban Setting) cohort study performed in Amsterdam. Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer-Lemeshow test). We identified 25 studies containing 29 models for prevalent or undiagnosed T2DM. C-statistics varied between 0.77-0.92 in Dutch, 0.66-0.83 in South Asian Surinamese, 0.70-0.82 in African Surinamese, 0.61-0.81 in Ghanaian, 0.69-0.86 in Turkish, and 0.69-0.87 in the Moroccan populations. The C-statistics were generally lower among the South Asian Surinamese, African Surinamese, and Ghanaian populations and highest among the Dutch. Calibration was poor (Hosmer-Lemeshow p < 0.05) for all models except one.

Conclusions: Generally, risk models for prevalent or undiagnosed T2DM show moderate to good discriminatory ability in different ethnic populations living in the Netherlands, but poor calibration. Therefore, these models should be recalibrated before use in clinical practice and should be adapted to the situation of the population they are intended to be used in.
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http://dx.doi.org/10.5334/gh.846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880001PMC
February 2021

Adherence to Drinking Guidelines and Reasons for Alcohol Consumption Cessation in the Southern Cone of Latin America - Findings from the CESCAS Study.

Glob Heart 2021 Jan 4;16(1). Epub 2021 Jan 4.

Instituto de Efectividad Clínica y Sanitaria, Buenos Aires, AR.

Introduction: Alcohol consumption is a risk factor for morbidity and mortality globally. Consumption levels in Southern Latin America are among the highest in the world.

Objectives: To describe consumption patterns and adherence to guidelines in the general adult population of Southern Latin America, as well as exploration of reasons for alcohol cessation and the advising role of the health worker in this decision.

Methods: In 7,520 participants from the Centro de Excelencia en Salud Cardiovascular para el America del Sur (CESCAS) cohort, consumption patterns were described and the proportion excessive drinkers (i.e. >7 units/week for women and >14 for men or binge drinking: >4 (women) or >5 (men) units at a single occasion) was calculated. Former drinkers were asked if they had quit alcohol consumption on the advice of a health worker and/or because of health reasons. Furthermore, among former drinkers, multivariable logistic regression analysis was performed to assess which participant characteristics were independently associated with the chance of quitting consumption on a health worker's advice.

Results: Mean age was 54.8 years (SD = 10.8), 42% was male. Current drinking was reported by 44.6%, excessive drinking by 8.5% of the population. In former drinkers, 23% had quit alcohol consumption because of health reasons, half of them had additionally quit on the advice of a health worker. The majority of former drinkers however had other, unknown, reasons. When alcohol cessation was based on a health worker's advice, sex, country of residence, educational status and frequency of visiting a physician were independent predictors.

Conclusion: In this Southern American population-based sample, most participants adhered to the alcohol consumption guidelines. The advising role of the health worker in quitting alcohol consumption was only modest and the motivation for the majority of former drinkers remains unknown. A more detailed assessment of actual advice rates and exploration of additional reasons for alcohol cessation might be valuable for alcohol policy making.
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http://dx.doi.org/10.5334/gh.840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792452PMC
January 2021

CONQUER: an interactive toolbox to understand functional consequences of GWAS hits.

NAR Genom Bioinform 2020 Dec 27;2(4):lqaa085. Epub 2020 Oct 27.

Department of Cell and Chemical Biology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.

Numerous large genome-wide association studies have been performed to understand the influence of genetics on traits. Many identified risk loci are in non-coding and intergenic regions, which complicates understanding how genes and their downstream pathways are influenced. An integrative data approach is required to understand the mechanism and consequences of identified risk loci. Here, we developed the R-package CONQUER. Data for SNPs of interest are acquired from static- and dynamic repositories (build GRCh38/hg38), including GTExPortal, Epigenomics Project, 4D genome database and genome browsers. All visualizations are fully interactive so that the user can immediately access the underlying data. CONQUER is a user-friendly tool to perform an integrative approach on multiple SNPs where risk loci are not seen as individual risk factors but rather as a network of risk factors.
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http://dx.doi.org/10.1093/nargab/lqaa085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671384PMC
December 2020

Recruitment of Participants for a 3D Virtual Supermarket: Cross-sectional Observational Study.

JMIR Form Res 2021 Feb 9;5(2):e19234. Epub 2021 Feb 9.

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

Background: Virtual supermarkets offer a practical and affordable setting to test the efficacy of different pricing and nudging strategies before they are implemented in the real world. Despite the advantages of using virtual supermarkets for this purpose, conducting studies in online settings is challenging with regard to recruitment and retention of sufficient and suitable participants.

Objective: To describe cost, time, and retention with regard to participants recruited using various strategies and potential sociodemographic differences between participants recruited via different strategies.

Methods: This cross-sectional study used data from a randomized controlled trial in which 455 Dutch adults with low and high educational levels were invited to shop 5 times in a 3D virtual supermarket. Participants were recruited via social media and flyers. A log that tracked the costs of and time spent on the different recruitment strategies was kept by the study team. Outcome measures included the cost of recruitment strategies, the time investment by researchers, and recruitment and attrition rates of participants in the study.

Results: The median age of study completers was 31.0 (IQR 25.0) and 157 out of 346 study completers (45.4%) were highly educated. Out of the 455 included participants, 235 (51.6%) were recruited via social media campaigns, 131 (28.8%) via home-delivered flyers, 38 (8.4%) via flyers directly distributed by the study team, and 46 (10.1%) via word-of-mouth. Of all paid recruitment strategies, social media campaigns were the cheapest and least time-consuming, whereas the distribution of flyers by the study team was the most expensive and time-consuming recruitment strategy. Age, sex, overweight status, employment situation, and number of adults within the household varied by recruitment strategy.

Conclusions: Using different recruitment strategies resulted in the efficient recruitment of a representative study sample and retention of participants was relatively high. While "word-of-mouth" was the most cost- and time-effective recruitment strategy, using only one type of recruitment strategy could result in a demographically skewed study population.
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http://dx.doi.org/10.2196/19234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902190PMC
February 2021

Reply to: "six months vitamin K treatment does not affect systemic arterial calcification or bone mineral density in diabetes mellitus 2".

Eur J Nutr 2021 04 9;60(3):1703-1704. Epub 2021 Feb 9.

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1007/s00394-020-02470-3DOI Listing
April 2021

Prevalence of ECG abnormalities in people with type 2 diabetes: The Hoorn Diabetes Care System cohort.

J Diabetes Complications 2021 02 26;35(2):107810. Epub 2020 Nov 26.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of General Practice Medicine, Amsterdam Public Health Research Institute, De Boelelaan 1117, Amsterdam, the Netherlands.

Aims: The American Diabetes Association, and the joint European Society of Cardiology and European Association for the Study of Diabetes guidelines recommend a resting ECG in people with type 2 diabetes with hypertension or suspected cardiovascular disease (CVD). However, knowledge on the prevalence of ECG abnormalities is incomplete. We aimed to analyse the prevalence of ECG abnormalities and their cross-sectional associations with cardiovascular risk factors in people with type 2 diabetes.

Methods: We used data of the Diabetes Care System cohort obtained in 2018. ECG abnormalities were defined using the Minnesota Classification and categorised into types of abnormalities. The prevalence was calculated for the total population (n = 8068) and the subgroup of people without a history of CVD (n = 6494). Logistic regression models were used to asses cross-sectional associations.

Results: Approximately one-third of the total population had minor (16.0%) or major (13.1%) ECG abnormalities. Of the participants without a CVD history, approximately one-quarter had minor (14.9%) or major (9.1%) ECG abnormalities, and for those with hypertension or very high CVD risk, the prevalence was 27.5% and 39.6%, respectively. ECG abnormalities were significantly and consistently associated with established CVD risk factors.

Conclusions: Resting ECG abnormalities are common in all people with type 2 diabetes (29.1%), including those without a history of CVD (24.0%), and their prevalence is related to traditional cardiovascular risk factors such as older age, male sex, hypertension, lower HDL cholesterol, higher BMI, and smoking behaviour.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107810DOI Listing
February 2021

Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study.

PLoS One 2020 30;15(11):e0242360. Epub 2020 Nov 30.

Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.

Aim: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.

Methods: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders.

Results: At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose.

Conclusions: Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242360PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703960PMC
January 2021

Ultra-processed food consumption patterns among older adults in the Netherlands and the role of the food environment.

Eur J Nutr 2021 Aug 24;60(5):2567-2580. Epub 2020 Nov 24.

Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1089A, 1081 BT, Amsterdam, The Netherlands.

Purpose: To describe the patterns of ultra-processed foods (UPFs) consumption in the Netherlands; to test if exposure to the food environment is associated with UPFs consumption; and if this association differed across educational levels and neighbourhood urbanisation.

Methods: Cross-sectional study using 2015-data of 8104 older adults from the Dutch EPIC cohort. Proportion of UPFs consumption was calculated from a validated food-frequency questionnaire. Exposure to the food environment was defined as proximity and availability of supermarkets, fast-food restaurants, full-service restaurants, convenience stores, candy stores and cafés. Consumption of UPFs was expressed as both percentage of total grams and total kilocalories.

Results: The study population was aged 70(± 10 SD) years and 80.5% was female. Average UPFs consumption was 17.8% of total food intake in grams and 37% of total energy intake. Those who consumed greater amounts of UPFs had a poorer overall diet quality. Adjusted linear regression models showed that closer proximity and larger availability to any type of food retailer was associated with lower UPFs consumption (both in grams and kilocalories). Somewhat stronger significant associations were found for proximity to restaurants (β = - 1.6%, 95% confidence interval (CI) = - 2.6; - 0.6), and supermarkets (β = - 2.2%, 95%CI = - 3.3; - 1.1); i.e., Individuals living within 500 m from the closest supermarket, as compared to 1500 m, had 2.6% less calories from UPFs. No differences were found on analyses stratified for urbanisation and education.

Conclusions: Using various measures of exposure to the food environment, we found that exposure to restaurants and supermarkets was associated with somewhat lower consumption of UPFs.
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http://dx.doi.org/10.1007/s00394-020-02436-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275501PMC
August 2021

Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Hypertension: A Mendelian Randomization Study.

Hypertension 2020 12 2;76(6):1971-1979. Epub 2020 Nov 2.

From the Department of Surgical Sciences, Uppsala University, Sweden (S.v.O., S.C.L.).

Hypertension is a major risk factor for cardiovascular disease and mortality. To identify targets for the prevention of hypertension and its associated disease burden, we used the 2-sample Mendelian randomization method to investigate the causal associations of 18 cardiovascular risk factors and lifestyle behaviors with hypertension. From European-descent genome-wide association studies, we selected genetic variants (<5×10) for type 2 diabetes, fasting glucose, lipids, body mass index, smoking, alcohol and coffee consumption, physical activity, sleep duration, insomnia, and educational level. We extracted the genetic associations with hypertension from 2 European cohorts: the FinnGen Study (15 870 cases and 74 345 controls) and UK Biobank (54 358 cases and 408 652 controls). The inverse-variance weighted method was used as main analysis method. Genetically predicted triglycerides (pooled odds ratio [OR] per 1 SD, 1.17 [1.10-1.25]), body mass index (OR per 1 SD, 1.42 [1.37-1.48]), alcohol dependence (OR, 1.10 [1.06-1.13]), and insomnia (OR, 1.17 [1.13-1.20]) were associated with a higher odds of hypertension. Higher genetically predicted high-density lipoprotein cholesterol (OR per 1 SD, 0.88 [0.83-0.94]) and educational level (OR per 1 SD, 0.56 [0.54-0.59]) were associated with a lower odds of hypertension. Suggestive evidence was obtained for type 2 diabetes, smoking initiation and alcohol consumption with a higher hypertension odds, and longer sleep duration with a lower hypertension odds. This Mendelian randomization study identified high-density lipoprotein cholesterol, triglycerides, body mass index, alcohol dependence, insomnia, and educational level as causal risk factors for hypertension. This implicates that these modifiable risk factors are important targets in the prevention of hypertension.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15761DOI Listing
December 2020

Natriuretic peptides for the detection of diastolic dysfunction and heart failure with preserved ejection fraction-a systematic review and meta-analysis.

BMC Med 2020 10 30;18(1):290. Epub 2020 Oct 30.

Department of Epidemiology & Data Science, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, VU University Medical Centre, De Boelelaan 1089a, 1081HV, Amsterdam, The Netherlands.

Background: An overview of the diagnostic performance of natriuretic peptides (NPs) for the detection of diastolic dysfunction (DD) and heart failure with preserved ejection fraction (HFpEF), in a non-acute setting, is currently lacking.

Methods: We performed a systematic literature search in PubMed and Embase.com (May 13, 2019). Studies were included when they (1) reported diagnostic performance measures, (2) are for the detection of DD or HFpEF in a non-acute setting, (3) are compared with a control group without DD or HFpEF or with patients with heart failure with reduced ejection fraction, (4) are in a cross-sectional design. Two investigators independently assessed risk of bias of the included studies according to the QUADAS-2 checklist. Results were meta-analysed when three or more studies reported a similar diagnostic measure.

Results: From 11,728 titles/abstracts, we included 51 studies. The meta-analysis indicated a reasonable diagnostic performance for both NPs for the detection of DD and HFpEF based on AUC values of approximately 0.80 (0.73-0.87; I = 86%). For both NPs, sensitivity was lower than specificity for the detection of DD and HFpEF: approximately 65% (51-85%; I = 95%) versus 80% (70-90%; I = 97%), respectively. Both NPs have adequate ability to rule out DD: negative predictive value of approximately 85% (78-93%; I = 95%). The ability of both NPs to prove DD is lower: positive predictive value of approximately 60% (30-90%; I = 99%).

Conclusion: The diagnostic performance of NPs for the detection of DD and HFpEF is reasonable. However, they may be used to rule out DD or HFpEF, and not for the diagnosis of DD or HFpEF.
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http://dx.doi.org/10.1186/s12916-020-01764-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599104PMC
October 2020

The Association of Vitamin D and Vitamin K Status with Subclinical Measures of Cardiovascular Health and All-Cause Mortality in Older Adults: The Hoorn Study.

J Nutr 2020 12;150(12):3171-3179

Department of Epidemiology and Data Science, Amsterdam University Medical Center, Amsterdam, The Netherlands.

Background: A low vitamin D and K status has been associated with increased cardiovascular disease (CVD) risk but the evidence of their combined effect on cardiovascular health is limited.

Objectives: Our study aimed to investigate the prospective association of vitamin D and K status with subclinical measures of cardiovascular health and all-cause mortality among a population of Dutch Caucasians.

Methods: We performed an observational prospective study on 601 participants of the Hoorn Study (mean ± SD age: 70 ± 6 y, 50.4% women, BMI: 27.2 ± 4.0 kg/m2), of whom 321 underwent an echocardiogram in 2000-2001 and 2007-2009. Vitamin D and K status was assessed at baseline by serum 25-hydroxyvitamin D [25(OH)D] and plasma desphospho-uncarboxylated matrix-gla protein (dp-ucMGP)-high concentrations indicate low vitamin K status. Vital status was assessed from baseline until 2018. We studied the association of categories of 25(OH)D (stratified by the clinical cutoff of 50 mmol/L) and dp-ucMGP (stratified by the median value of 568 pmol/L) with echocardiographic measures using linear regression and with all-cause mortality using Cox regression, adjusted for confounders.

Results: Compared with markers of normal vitamin D and K status, markers of low vitamin D and K status were prospectively associated with increased left ventricular mass index (5.9 g/m2.7; 95% CI: 1.8, 10.0 g/m2.7). Participants with low vitamin D and K status were also at increased risk of all-cause mortality with an HR of 1.64 (95% CI: 1.12, 2.39) compared with normal vitamin D and K status.

Conclusions: A combination of low vitamin D and K status is associated with adverse cardiac remodeling and increased risk of all-cause mortality in men and women. Future studies should investigate whether vitamin D and K supplementation could help to improve cardiovascular health and to decrease CVD risk.
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http://dx.doi.org/10.1093/jn/nxaa293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726120PMC
December 2020

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

Alcohol consumption patterns across Europe and adherence to the European guidelines in coronary patients: Findings from the ESC-EORP EUROASPIRE V survey.

Atherosclerosis 2020 11 17;313:35-42. Epub 2020 Sep 17.

Julius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Amsterdam University Medical Center, Location VUmc, Amsterdam Cardiovascular Sciences Research Institute, Department of Epidemiology and Biostatistics, Amsterdam, the Netherlands.

Background And Aims: Alcohol consumption is an important risk factor for cardiovascular morbidity and mortality worldwide. The highest levels of alcohol consumption are observed in Europe, where alcohol as contributing cause of coronary heart disease (CHD) is also most significant. We aimed to describe alcohol consumption patterns across European regions and adherence to the current guidelines in patients with a recent CHD event.

Methods: The ESC-EORP survey (EUROASPIRE V) has been conducted in 2016-2017 at 131 centers in 27 European countries in 7350 patients with a recent CHD. Median alcohol consumption, as well as the proportion of abstainers and excessive drinkers (i.e. >70 g/week for women and >140 for men, as recommended by the European guidelines on cardiovascular prevention), was calculated for each region. To assess adherence to guidelines, proportions of participants who were advised to reduce excessive alcohol consumption and participants who were incorrectly not advised were calculated per region.

Results: Mean age was 64 years (SD: 9.5), 75% were male. Abstention rates were 53% in males and 77% in females, whereas excessive drinking was reported by 9% and 5% of them, respectively. Overall, 57% of the participants were advised to reduce alcohol consumption. In the total population, 3% were incorrectly not advised, however, this percentage differed per region (range: 1%-9%). In regions where alcohol consumption was highest, participants were less often advised to reduce their consumption.

Conclusion: In this EUROASPIRE V survey, the majority of CHD patients adhere to the current drinking guidelines, but substantial heterogeneity exists between European regions.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.09.009DOI Listing
November 2020
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