Yvonne T van der Schouw

Maastricht Universitair Medisch Centrum, Maestricht, Limburg, Netherlands

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Publications (447)2239.78 Total impact

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    ABSTRACT: Objective Women with a history of preeclampsia are at increased risk for future cardiovascular disease. Determination of cardiovascular biomarkers may be useful to understand the pathophysiological mechanism of cardiovascular disease development in these women. Methods We performed an analysis in the Preeclampsia Risk EValuation in FEMales study, a retrospective cohort consisting of 339 women with a history of early preeclampsia and 332 women after normotensive pregnancy. Women attended a follow-up visit ten years after the index pregnancy. A subset of 8 different cardiovascular biomarkers was investigated, reflecting inflammatory, metabolic, thrombotic and endothelial function markers. Associations between PE and these novel biomarkers were analyzed by linear regression analysis and adjusted for traditional cardiovascular risk factors. Results Mean age of 671 women of the PREVFEM cohort was 39 years and women were on average 10 years post index pregnancy. Women post preeclampsia had significantly higher levels of SE-selectin (adjusted difference 4.55, 99%CI 0.37; 8.74) and PAPPA (adjusted difference 19.08; 99%CI 13.18; 24.99), whereas ApoB (adjusted difference −0.23 99%CI −0.32; −0.14) was inversely associated with preeclampsia, compared to women with a previous normotensive pregnancy. Adiponectin, leptin, sICAM-1, sVCAM-1 and PAI-1 were not different between both groups. Conclusion We demonstrated an independent association of preeclampsia with SE-selectin and PAPPA (markers of vascular dysfunction), which may contribute to future cardiovascular events in women post preeclampsia. However, ApoB (an apolipoprotein) was significantly lower and could point at a protective mechanism in our PE study women.
    Atherosclerosis 11/2014; 237(1):117–122. · 3.71 Impact Factor
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    ABSTRACT: Phytosterols (PSs) are known to lower low-density lipoprotein cholesterol (LDL-C), an established risk factor for cardiovascular disease (CVD). Whether a high intake of PS reduces CVD risk is unknown. This observational study aimed to investigate the associations between intake of naturally occurring PSs, blood lipids and CVD risk.
    European Journal of Preventive Cardiology 10/2014; · 3.90 Impact Factor
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    ABSTRACT: Although diet is related to chronic disease risk and mortality, its association with total disease burden is not clear.
    American Journal of Clinical Nutrition 10/2014; 100(4):1158-65. · 6.50 Impact Factor
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    ABSTRACT: Various cardiovascular prediction models have been developed for patients with type 2 diabetes. Their predictive performance in new patients is mostly not investigated. This study aims to quantify the predictive performance of all cardiovascular prediction models developed specifically for diabetes patients.
    Heart (British Cardiac Society) 09/2014; · 5.01 Impact Factor
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    ABSTRACT: Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. Findings Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05–0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18–0·43), waist circumference (0·32 cm, 0·16–0·47), plasma insulin concentration (1·62%, 0·53–2·72), and plasma glucose concentration (0·23%, 0·02–0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00–1·05); the rs12916-T allele association was consistent (1·06, 1·03–1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18–1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10–0·38 in all trials; 0·33 kg, 95% CI 0·24–0·42 in placebo or standard care controlled trials and −0·15 kg, 95% CI −0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9–6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06–1·18 in all trials; 1·11, 95% CI 1·03–1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04–1·22 in intensive-dose vs moderate dose trials). Interpretation The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. Funding The funding sources are cited at the end of the paper.
    The Lancet. 09/2014;
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    ABSTRACT: Introduction Breast cancer is the most prevalent cancer in women, with slightly more than ten percent developing the disease in Western countries. Mammography screening is a well established method to detect breast cancer. Aims The aim of the position statement is to review critically the advantages and shortcomings of population based mammography screening. Materials and methods Literature review and consensus of expert opinion. Results and conclusion Mammography screening programmes vary worldwide. Thus there are differences in the age at which screening is started and stopped and in the screening interval. Furthermore differences in screening quality (such as equipment, technique, resolution, single or double reading, recall rates) result in a sensitivity varying from 70 to 94% between studies. Reporting results of screening is subject to different types of bias such as overdiagnosis. Thus because of the limitations of population-based mammography screening programmes an algorithm for individualized screening is proposed.
    Maturitas 09/2014; · 2.84 Impact Factor
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    ABSTRACT: Women with a history of preeclampsia are at increased risk for future cardiovascular disease. Determination of cardiovascular biomarkers may be useful to understand the pathophysiological mechanism of cardiovascular disease development in these women.
    Atherosclerosis 09/2014; 237(1):117-122. · 3.71 Impact Factor
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    ABSTRACT: Studies investigating the relation between risk profiles and cardiovascular disease have measured risk at baseline only. We investigated maintenance and changes of risk profiles over time and their potential impact on incident cardiovascular disease.
    European Journal of Preventive Cardiology 07/2014; · 3.90 Impact Factor
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    ABSTRACT: Global and national dietary guidelines have been created to lower chronic disease risk. The aim of this study was to assess whether greater adherence to the WHO guidelines (Healthy Diet Indicator (HDI)); the Dutch guidelines for a healthy diet (Dutch Healthy Diet-index (DHD-index)); and the Dietary Approaches to Stop Hypertension (DASH) diet was associated with a lower risk of cardiovascular disease (CVD), coronary heart disease (CHD) or stroke.
    International journal of cardiology. 07/2014;
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    ABSTRACT: Cardiovascular disease is an important cause of disability in activities of daily living (ADL) through its effect on physical functioning. However, it is unclear whether subclinical vascular abnormalities and rate of change in subclinical vascular abnormalities is also associated with an impaired physical ability and with ADL disability. In a longitudinal study, 490 middle-aged and older persons were included. Physical ability was measured using the Short Physical Performance Battery and ADL disability using a questionnaire on self-reported basic and instrumental ADL. Subclinical vascular abnormalities were measured by pulse wave velocity (PWV) and carotid intima media thickness (CIMT, in men only). Longitudinal associations between baseline markers of subclinical vascular abnormalities, their rate of change, and change in physical ability or ADL disability were assessed using generalized estimation equation models. After adjustment for confounders, higher baseline PWV, change in PWV, baseline CIMT (in men) and change in CIMT (in men) were associated with a higher rate of change in physical ability (regression coefficients 0.035, 95% CI [0.018; 0.052]; 0.047, 95% CI [0.024; 0.069]; 0.214, 95% CI [0.070; 0.358] and 0.148, 95% CI [0.019; 0.277], respectively). No relations were found for change in ADL disability. In subjects with incident cardiovascular disease, higher change in PWV was associated with a higher rate of change in ADL disability (regression coefficient 0.054, 95% CI [0.001; 0.106]). The present study showed that subclinical vascular abnormalities and rate of change were associated with higher rate of change in physical ability. The association between (change in) subclinical vascular abnormalities and ADL disability tended to be stronger in persons with incident and prevalent cardiovascular disease. These data may suggest that ADL decline is more a direct effect of experienced clinically manifest vascular events rather than the effect of progression of subclinical vascular abnormalities.
    Experimental gerontology. 06/2014;
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    ABSTRACT: To investigate the association of plasma phylloquinone concentrations with coronary artery calcification (CAC) and vascular calcification.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2014; · 6.34 Impact Factor
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    ABSTRACT: Experimental data suggest a role for advanced glycation endproducts (AGEs) in cardiovascular disease (CVD), particularly in type 2 diabetes (T2DM). However, epidemiological evidence of an association between high plasma AGEs and increased cardiovascular risk remains inconclusive. Therefore, in a case-cohort study comprising 134 cardiovascular cases and a random subcohort of 218 individuals (including 65 cardiovascular cases), all with T2DM and nested in the EPIC-NL study, plasma levels of protein-bound N(ε)-(carboxymethyl)lysine (CML), N(ε)-(carboxyethyl)lysine (CEL) and pentosidine were measured with liquid-chromatography. AGEs were loge-transformed, combined in a z-score and the association with incident cardiovascular events was analysed with Cox-proportional hazard regression, adapted for case-cohort design (Prentice method). After multivariable adjustment (sex, age, cohort status, diabetes duration, total cholesterol to HDL-cholesterol ratio, smoking, systolic blood pressure, BMI, blood pressure-, cholesterol- and glucose-lowering treatment, prior cardiovascular events and triglycerides) higher plasma AGE z-scores were associated with higher risk of incident cardiovascular events in individuals without prior cardiovascular events, (HR: 1.31 (95%CI: 1.06-1.61)). A similar trend was observed in individuals with prior cardiovascular events (HR: 1.37 (95%CI: 0.63-2.98)). In conclusion, high plasma AGEs were associated with incident cardiovascular events in individuals with T2DM. These results underline the potential importance of AGEs in development of CVD.
    Diabetes 05/2014; · 7.90 Impact Factor
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    ABSTRACT: High vitamin K intake is associated with reduced coronary heart disease (CHD). This is thought to be mediated by increased activation of the vitamin K dependent matrix Gla protein (MGP). Desphospho-uncarboxylated MGP (dp-ucMGP) is associated with both vitamin K status and vascular calcification. However, the association between dp-ucMGP with CHD and stroke in the general population has not been investigated to date. To investigated the association of dp-ucMGP with incident CHD or stroke. A prospective case-cohort study with a representative baseline sample of 1406 participants and 1154 and 380 incident cases of CHD and stroke, respectively, was nested within the EPIC-NL study. Circulating dp-ucMGP concentrations were measured by ELISA technique in baseline plasma samples. The incidence of fatal and non-fatal CHD and stroke was obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs) per standard deviation (SD) and per quartile of circulating dp-ucMGP levels,. The average follow-up was 11.5 years. Dp-ucMGP concentrations were not associated with CHD risk with a HR per SD of 1.00 (95% CI: 0.93-1.07) and a HR Q4 vs Q1 of 0.94 (95% CI: 0.79-1.13) after adjustment for cardiovascular risk factors. Dp-ucMGP was not associated with stroke risk (HRSD 0.98;95% CI: 0.90-1.08 and a HR Q4 vs Q1 of 1.09;95% CI: 0.78-1.51). This study could not confirm that high dp-ucMGP concentrations, reflecting a poor vitamin K status, are associated with increased CHD or stroke risk in the general population. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 05/2014; · 6.08 Impact Factor
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    ABSTRACT: Are fragile X mental retardation gene 1 (FMR1) CGG repeats in the normal and intermediate range (up to 55 repeats) associated with primary ovarian insufficiency (POI) in a large case-control study? No association was found between CGG repeats of intermediate size and POI compared with controls. CGG repeats in the FMR1 gene in the premutation range (55-200 repeats) have consistenly associated with POI. Intermediate range CGG repeats have been considered for a potential association with POI. A case-control study in 375 well-phenotyped Dutch women diagnosed with POI and 3368 controls with natural menopause ≥40 years of age. The FMR1 CGG repeat number was determined by PCR amplification in women diagnosed with POI and women with a known age at natural menopause ≥40 years. The prevalence of intermediate sized CGG repeats (45-54 repeats) was compared between POI cases and controls using Fisher's exact test. Differences in mean CGG repeat lengths on allele 1 and allele 2 between POI cases and controls were tested using analysis of variance. The frequency of intermediate sized CGG repeats on the allele with the longest triple repeat number was not statistically significantly different between POI cases and controls (2.7 and 3.8%, respectively, odds ratio 0.72, 95% confidence interval: 0.38-1.39, P = 0.38). In women with POI, linear regression analysis for age at POI diagnosis and CGG repeat size also failed to show any association (β = -0.018, P = 0.74). FMR1 CGG repeat lengths in POI cases and controls were genotyped in two different laboratories. The distributions of CGG repeats may vary among the different ethnic populations in our study. Also, in our study women with primary amenorrhea (N = 17) were included in the POI group. We found no association between intermediate sized CGG repeats and POI compared with controls. Therefore, a role for FMR1 CGG repeat sizes up to 55 repeats in the ovarian ageing process may be questioned. Moreover, there seems limited value in the evaluation of normal- and intermediate FMR1 repeat size in the diagnostic work-up of women affected by POI, or for prognostic purposes in women at risk of developing POI. The Prospect-EPIC study was funded by 'Europe Against Cancer' Program of the European Commission (SANCO); the Dutch Ministry of Health; the Dutch Cancer Society; ZonMW the Netherlands Organization for Health Research and Development; World Cancer Research Fund (WCRF) and the Dutch Heart Association.
    Human Reproduction 05/2014; · 4.67 Impact Factor
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    ABSTRACT: Prospective cohort studies recruit relatively healthy population samples, resulting in lower morbidity and mortality rates than in the source population. This is known as the healthy volunteer effect. The aim of this study was to define the magnitude and the development over time of the healthy volunteer effect in the EPIC-NL cohort. We studied mortality rates in the EPIC-NL cohort, which comprises 37 551 men and women aged 20-70 years at recruitment in 1993-97. The date and cause of death of deceased participants until 2010 were obtained through linkage with the municipal registry and Statistics Netherlands. Standardized mortality ratios (SMRs) were computed by dividing the observed number of deaths by the number of deaths expected from the general Dutch population. Additionally, standardized incidence ratios were calculated to compare cancer incidence. After an average follow-up of 14.9 years, 3029 deaths were documented. Overall mortality in men [SMR 73.5%, 95% confidence interval (CI): 68.1-79.3] and women (SMR 65.9%, 95% CI: 63.2-68.6) was lower compared with the general population for the whole follow-up period. The SMRs clearly increased over the follow-up period. Among women, the SMR was lower for death due to cardiovascular diseases than death due to cancer. Cancer incidence was also lower in EPIC-NL than in the general population (SMR 78.3 and 82.7% for men and women, respectively). The results show a healthy volunteer effect in the EPIC-NL cohort, which tapers off with longer follow-up. Therefore, in the first years of follow-up, power might not be sufficient to detect small associations.
    The European Journal of Public Health 04/2014; · 2.52 Impact Factor
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    ABSTRACT: Food choices influence health status, but also have a great impact on the environment. The production of animal-derived foods has a high environmental burden, whereas the burden of refined carbohydrates, vegetables and fruit is low. The aim of this study was to investigate the associations of greenhouse gas emission (GHGE) and land use of usual diet with mortality risk, and to estimate the effect of a modelled meat substitution scenario on health and the environmental. The usual diet of 40011 subjects in the EPIC-NL cohort was assessed using a food frequency questionnaire. GHGE and land use of food products were based on life cycle analysis. Cox proportional hazard ratios (HR) were calculated to determine relative mortality risk. In the modelled meat-substitution scenario, one-third (35 gram) of the usual daily meat intake (105 gram) was substituted by other foods. During a follow-up of 15.9 years, 2563 deaths were registered. GHGE and land use of the usual diet were not associated with all-cause or with cause-specific mortality. Highest vs. lowest quartile of GHGE and land use adjusted hazard ratios for all-cause mortality were respectively 1.00 (95% CI: 0.86-1.17) and 1.05 (95% CI: 0.89-1.23). Modelled substitution of 35 g/d of meat with vegetables, fruit-nuts-seeds, pasta-rice-couscous, or fish significantly increased survival rates (6-19%), reduced GHGE (4-11%), and land use (10-12%). There were no significant associations observed between dietary-derived GHGE and land use and mortality in this Dutch cohort. However, the scenario-study showed that substitution of meat with other major food groups was associated with a lower mortality risk and a reduced environmental burden. Especially when vegetables, fruit-nuts-seeds, fish, or pasta-rice-couscous replaced meat.
    Environmental Health 04/2014; 13(1):27. · 2.71 Impact Factor
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    ABSTRACT: The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥7.5%) risk. During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.
    JAMA The Journal of the American Medical Association 03/2014; 311(12):1225-33. · 29.98 Impact Factor
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    ABSTRACT: Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
    The American Journal of Human Genetics 02/2014; · 11.20 Impact Factor

Publication Stats

10k Citations
2,239.78 Total Impact Points


  • 2014
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 1999–2014
    • University Medical Center Utrecht
      • Julius Center for Health Sciences and Primary Care
      Utrecht, Utrecht, Netherlands
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 2013
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, England, United Kingdom
    • Université Paris 13 Nord
      Île-de-France, France
  • 2012
    • Massachusetts General Hospital
      • Center for Human Genetic Research
      Boston, MA, United States
    • University of Oxford
      • Nuffield Department of Clinical Medicine
      Oxford, ENG, United Kingdom
  • 2011
    • The University of Western Ontario
      London, Ontario, Canada
  • 2008–2011
    • University of Groningen
      • • Department of Epidemiology
      • • Department of Pathology and Medical Biology
      • • Laboratory for Medical Microbiology
      Groningen, Province of Groningen, Netherlands
    • Persian Gulf Research And Studies Center
      Bandar Emām Khomeynī, Ostan-e Khuzestan, Iran
    • National Institute for Public Health and the Environment (RIVM)
      • Centre for Nutrition and Health
      Utrecht, Utrecht, Netherlands
    • University of Wuerzburg
      Würzburg, Bavaria, Germany
  • 2010
    • Isala Klinieken
      • Department of Cardiology
      Zwolle, Provincie Overijssel, Netherlands
  • 2009
    • Hogeschool Utrecht
      Utrecht, Utrecht, Netherlands
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
    • German Cancer Research Center
      • Division of Cancer Epidemiology
      Heidelberg, Baden-Wuerttemberg, Germany
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany
    • University of Melbourne
      Melbourne, Victoria, Australia
  • 1990–2008
    • Wageningen University
      • Division of Human Nutrition
      Wageningen, Provincie Gelderland, Netherlands
  • 1992–2007
    • Maastricht University
      • • Interne Geneeskunde
      • • Humane Biologie
      Maastricht, Provincie Limburg, Netherlands
  • 2006
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2005–2006
    • Erasmus Universiteit Rotterdam
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
    • Harvard University
      • Department of Nutrition
      Boston, MA, United States
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
  • 1996–2006
    • Universiteit Utrecht
      • • Julius Centre for Health Sciences and Primary Care
      • • University Medical Center Utrecht
      • • Department of Epidemiology
      Utrecht, Provincie Utrecht, Netherlands
  • 2001
    • Rehabilitation Medical Center Groot Klimmendaal
      Arnheim, Gelderland, Netherlands
  • 1992–1995
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands