Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Blood Pressure Regulation
Mensink, M.R. - \ 2019
blood pressure - heart rate - arteries - cardiovascular diseases - kidney diseases - hormones
The body has several mechanisms to regulate blood pressure. A distinction can be made between quick control and long-term regulation. Regulation of your blood pressure is essential, since hypertension is a major risk factor for cardiovascular- and kidney disease. This lesson is part of the WageningenX MOOC called 'Nutrition, Heart Disease and Diabetes'
Introduction to cardiometabolic diseases | WURcast
Geleijnse, J.M. - \ 2019
Wageningen :
diabetes - health care costs - cardiovascular diseases - kidney diseases
Diabetes is a chronic condition that is characterised by a high blood glucose level. Currently, there are 415 million diabetic patients worldwide, and this puts an enormous burden on our health care systems. In this video, professor Geleijnse introduces the topic of diabetes. You will learn the different types of diabetes and several risk factors. You will see that diabetes is related to both cardiovascular disease and chronic kidney disease, which is also a component of the cardiometabolic disease cluster.
Kidney function and specific mortality in 60-80 years old post-myocardial infarction patients: a 10-year follow-up study
Geleijnse, J.M. ; Hoogeveen, Ellen K. - \ 2017
n-3 fatty acids - cardiovascular diseases - post-myocardial infarction patients - kidney function
This research project studies the relation between kidney function and all-cause and specific mortality among older post-MI patients, without severe heart failure, who are treated with state-of-the-art pharmacotherapy. From 2002-2006, 4,561 Dutch post-MI patients were enrolled and followed until death or January 2012. We estimated Glomerular Filtration Rate (eGFR) with cystatin C (cysC) and creatinine (cr) using the CKD-EPI equations and analyzed the relation with any and major causes of death using Cox models and restricted cubic splines. Mean (SD) for age was 69y (5.6), 79% were men, 17% smoked, 21% had diabetes, 90% used antihypertensive drugs, 98% used antithrombotic drugs and 85% used statins. Patients were divided into four categories of baseline eGFRcysC: ≥90 (33%; reference), 60-89 (47%), 30-59 (18%), and <30 (2%) ml/min/1.73m2. Median follow-up was 6.4 y. During follow-up, 873 (19%) patients died: 370 (42%) from cardiovascular causes, 309 (35%) from cancer, and 194 (22%) from other causes. After adjustment for age, sex and classic cardiovascular risk factor, hazard ratios (95%-confidence intervals) for any death according to eGFRcysC category were: 1 (reference), 1.4 (1.1-1.7), 2.9 (2.3-3.6) and 4.4 (3.0-6.4). The hazard ratios of all-cause and cause-specific mortality increased linearly below kidney functions of 80 ml/min/1.73 m2. Weaker results were obtained for eGFRcr. To conclude, we found in optimal cardiovascular drug-treated post-MI patients an inverse graded relation between kidney function and mortality for both cardiovascular as well as non-cardiovascular causes. Risk of mortality increased linearly below kidney function of about 80 ml/min/1.73 m2.
Vascular effects of sodium and potassium intake
Gijsbers, Lieke - \ 2017
Wageningen University. Promotor(en): Marianne Geleijnse; Pieter van 't Veer. - Wageningen : Wageningen University - ISBN 9789463436267 - 161
sodium - potassium - vascular system - hypertension - blood pressure - mineral supplements - endothelium - blood vessels - heart rate - osmoregulation - human nutrition research - randomized controlled trials - cardiovascular diseases - natrium - kalium - vaatsysteem - hypertensie - bloeddruk - minerale supplementen - endotheel - bloedvaten - hartfrequentie - osmoregulatie - voedingsonderzoek bij de mens - gestuurd experiment met verloting - hart- en vaatziekten

Cardiovascular diseases (CVD) are the main cause of death worldwide. Annually, about 17.5 million people die from CVD, accounting for ~30% of deaths worldwide. Elevated blood pressure (BP) is a major risk factor for CVD and the largest single contributor to global mortality. BP is a modifiable risk factor that is largely determined by lifestyle factors, including diet. Dietary minerals, in particular sodium and potassium, play an important role in BP regulation. While adverse effects of sodium and beneficial effects of potassium on BP have repeatedly been shown in human intervention studies, evidence on other vascular effects of these dietary minerals is still scarce. Therefore, we investigated the BP effects of sodium and potassium intake in healthy humans in a broader (patho)physiological context, focusing also on endothelial function, arterial stiffness, fluid regulation and heart rate.

In Chapter 2, the effects of sodium and potassium supplementation on BP and arterial stiffness were examined by means of a randomized placebo-controlled crossover trial. Thirty-six untreated Dutch individuals with mildly elevated BP on a fully controlled diet that was relatively low in sodium (2-3 g/d) and potassium (2-3 g/d) received capsules with sodium (3 g/d), potassium (3 g/d) or placebo, for 4 weeks each, in random order. After each intervention, fasting office BP, 24-h ambulatory BP and measures of arterial stiffness were assessed. The results of this study showed that increased sodium intake strongly raised office and ambulatory systolic BP (7-8 mmHg) whereas increased potassium intake lowered systolic BP (3-4 mmHg). Potassium supplementation increased ambulatory HR, but office HR was not affected. Measures of arterial stiffness were not materially affected by increased sodium or potassium intake, possibly due to the relatively short intervention period.

In the same study we investigated the effects of increased sodium and potassium intake on the functional measure of endothelial function (flow-mediated dilation), and on a comprehensive set of biomarkers of endothelial dysfunction and low-grade inflammation (Chapter 3). Four weeks of supplemental sodium had no effect on brachial flow-mediated dilation, or on the blood biomarkers of endothelial dysfunction and low-grade inflammation, except for an increase in serum endothelin-1 (a biomarker of endothelial dysfunction). Potassium supplementation improved flow-mediated dilation by 1.2% and tended to lower the low-grade inflammation marker interleukin-8. This suggests that potassium may beneficially influence vascular health by improving endothelial function.

In a post-hoc analysis of the same study in 35 untreated individuals, the humoral effects of supplemental sodium and potassium were assessed using a panel of markers that are involved in osmoregulation and volume regulation (Chapter 4). Results showed that supplemental sodium increased plasma natriuretic peptides and plasma copeptin, and suppressed the renin-angiotensin system. Supplemental potassium decreased plasma MR-pro-ANP, increased plasma copeptin, and stimulated the renin-angiotensin system. These findings suggest that the mineral-induced changes in BP elicit several counter regulatory mechanisms to maintain volume homeostasis.

In Chapter 5, the effect of potassium supplementation on heart rate was assessed in a meta-analysis of 22 randomized, placebo-controlled trials in healthy adults. Overall, increasing potassium intake by 2-3 g/d for at least two weeks did not affect resting heart rate. 24-h Ambulatory heart rate was not significantly affected in subgroup analysis of 4 RCTs, including ours. Other subgroup analyses for characteristics of the study and study population also showed no significant effects, and there was no evidence for a dose-response relationship. These results suggest that increasing potassium intake is not expected to adversely affect heart rate in apparently healthy adults.

In Chapter 6, BP associations for sodium and potassium intake using different dietary assessment methods were examined. Data of 993 healthy Dutch adults not on antihypertensive medication were analyzed using a cross-sectional approach. Sodium and potassium intake were estimated from two non-consecutive 24-h urinary samples (considered as the gold standard), two non-consecutive web-based 24-h recalls, and a validated 180-item food frequency questionnaire (FFQ). This study showed no significant associations of sodium intake with BP, regardless of the dietary assessment method used. Potassium intake estimated from 24-h urine and FFQ was inversely associated with BP (~1.5 mmHg reduction per 1 g/d increment). This suggests that dietary assessment methods in cross-sectional studies may be inadequate for estimating the association of sodium intake with BP, but may yield reliable results for potassium intake.

As discussed in Chapter 7, the studies presented in this thesis indicate that increasing sodium intake from a recommended level to a level that is common in Western societies for four weeks strongly raises BP in individuals with an untreated mildly elevated BP. The results for endothelial function and arterial stiffness are inconclusive, and hence more (longer-term) studies are warranted. Increasing the intake of potassium lowers BP and improves endothelial function, even in individuals on a relatively low-sodium diet. Both sodium and potassium intake affected fluid parameters, likely indicating that compensatory responses are stimulated to maintain body fluid balance. Although in our RCT ambulatory heart rate was increased after supplemental potassium, the meta-analysis showed that increasing potassium intake is unlikely to affect heart rate in apparently healthy adults. When evaluating the effectiveness of sodium and potassium intake on cardiovascular health, results obtained from observational studies should be interpreted with caution, particularly for sodium intake.

Around the world people consume on average 9-12 g of salt and 2-4 g of potassium on a daily basis. A more optimal intake of sodium and potassium can be achieved through adherence to dietary guidelines and product reformulation by food industry. This could reduce BP by more than 10 mmHg and lower the number of cardiovascular deaths by at least one-quarter in Western populations.

Goede voeding voor het hart : zorg dat het klopt
Geleijnse, Marianne - \ 2016
Wageningen : Wageningen University & Research - ISBN 9789463430234 - 32
gezondheidsgedrag - voeding en gezondheid - hart- en vaatziekten - obesitas - roken - zout - levensstijl - health behaviour - nutrition and health - cardiovascular diseases - obesity - smoking - salt - lifestyle
Dietary epicatechnin and quercetin in cardiovascular health and disease
Dower, J.I. - \ 2016
Wageningen University. Promotor(en): Daan Kromhout; Marianne Geleijnse, co-promotor(en): Peter Hollman. - Wageningen : Wageningen University - ISBN 9789462577862 - 164 p.
cardiovascular disorders - cardiovascular diseases - epicatechin - quercetin - epidemiological surveys - genome analysis - chocolate - hart- en vaatstoornissen - hart- en vaatziekten - epicatechine - quercetine - epidemiologische onderzoeken - genoomanalyse - chocolade

Epidemiological studies showed that the consumption of flavonoid-rich foods such as cocoa and tea is associated with a lower risk of cardiovascular disease (CVD). Randomised controlled trials (RCTs) showed that cocoa and tea improved markers of cardiometabolic health including blood pressure, endothelial function, insulin resistance, arterial stiffness and inflammation.

Cocoa is particularly rich in the flavan-3-ol epicatechin and tea is the main dietary source of epicatechin and of the major flavonol quercetin. However, evidence on the individual roles of epicatechin and quercetin in the health effects of cocoa and tea is still scarce. Therefore, we estimated the strength of the association between epicatechin intake and CVD mortality in a prospective cohort study. Furthermore, we also investigated the effects of epicatechin and quercetin on markers of cardiometabolic health and gene expression, by means of two RCTs.

In Chapter 2, the association between epicatechin intake and CVD mortality was studied using data from the Zutphen Elderly Study, a cohort of 744 elderly Dutch men. During 25 years of follow-up, 329 men died from CVD and 148 from coronary heart disease (CHD). Results from this study showed that men in the highest tertile of epicatechin intake had a 38% lower risk of CHD mortality compared to men in the lowest tertile. For men with prevalent CVD, the risk of CVD mortality was 46% lower for men in the highest tertile of intake, compared to men in the lowest tertile. This is the first epidemiological study to have investigated the association between epicatechin intake and CVD mortality. Hence, more and larger cohort studies are required to confirm this association, possibly with a focus on populations with a high risk of CVD.

In Chapter 3, the chronic effects of pure epicatechin and quercetin on markers of cardiometabolic health were investigated by means of a RCT. Thirty-seven apparently healthy men and women aged 40–80 years consumed (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 weeks, in random order. Markers of cardiometabolic health were measured before and after each 4-week intervention. The results of this study showed that epicatechin improved insulin resistance and had a borderline significant effect on endothelial function. This suggests that epicatechin contributes to the cardioprotective effects of cocoa and tea, however, larger long-term RCTs are required to confirm these effects. Pure quercetin supplementation did not affect any of these markers of cardiometabolic health.

Using data from the same study, we investigated the effects of supplementation of pure epicatechin and quercetin on a comprehensive set of biomarkers of endothelial dysfunction and inflammation (Chapter 4). With the exception of sE-selectin (a biomarker of endothelial dysfunction), epicatechin supplementation did not beneficially influence any of the biomarkers, suggesting a lack of evidence for a role of epicatechin in inflammation. Quercetin also lowered sE-selectin as well as the inflammatory biomarker IL-1β and the overall z-score for inflammation. This suggests that quercetin may contribute to the cardioprotective effects of tea by reducing inflammation and possibly by improving endothelial function.

In the same study, the effects of pure epicatechin supplementation on whole genome gene expression profiles of circulating immune cells were also assessed (Chapter 5). Pure epicatechin supplementation modestly reduced gene expression related to inflammation signalling routes in circulating immune cells – routes which are known to play a role in cardiovascular health. However, there was no evidence that epicatechin affected pathways related to insulin resistance or endothelial function.

To directly compare the acute effects of pure epicatechin and epicatechin from dark chocolate on vascular function, we carried out an acute RCT in 20 apparently healthy men aged 40-80 years (Chapter 6). On three separate occasions, subjects consumed: 1) 70g dark chocolate (150 mg epicatechin) with two placebo capsules; 2) two pure epicatechin capsules (100 mg epicatechin) with 75g white chocolate and 3) two placebo capsules with 75g white chocolate (0 mg epicatechin). Endothelial function and arterial stiffness were measured before and two hours after each intervention. To determine epicatechin bioavailability, epicatechin metabolites were measured in blood samples taken at repeated intervals over a period of 8 hours. There was no significant difference in improvement in endothelial function or arterial stiffness between pure epicatechin and dark chocolate. There was also no difference in bioavailability of pure epicatechin and epicatechin from dark chocolate, when standardised per 100 mg of epicatechin. This suggests that epicatechin may contribute to the vascular effects of cocoa and that the bioavailability of pure epicatechin and epicatechin from dark chocolate is similar.

In the general discussion, the main findings of this thesis were first summarised. Methodological considerations related to cohort studies, such as the assessment of flavonoid intake and the possibility of residual confounding were also discussed. Issues related to the relevance of cardiometabolic markers in RCTs and the effect of cocoa flavan-3-ol bioavailability were addressed. Finally, suggestions for future research were put forward.

In conclusion, the results of this thesis suggest that epicatechin contributes to the cardioprotective effects of cocoa and tea. Epicatechin intake was inversely related to CHD mortality in elderly men, and to CVD mortality in men with prevalent CVD. The cardioprotective effects of epicatechin are likely mediated through improvements in insulin resistance and possibly endothelial function. In contrast, quercetin is unlikely to play a major role in the cardioprotective effects of tea. Results for quercetin from cohort studies are inconclusive, and based on the results of our chronic RCT, quercetin did not affect vascular function or insulin resistance, but may help to lower inflammation. Evidence of the role that individual flavonoids play in the aetiology of CVD is still limited. More studies with pure flavonoids are required to elucidate their role.

Dietary protein, blood pressure and mortality : the value of repeated measurements
Tielemans, S.M.A.J. - \ 2016
Wageningen University. Promotor(en): Marianne Geleijnse; Daan Kromhout, co-promotor(en): Hendriek Boshuizen. - Wageningen : Wageningen University - ISBN 9789462577916 - 169 p.
cardiovascular diseases - blood pressure - dietary protein - mortality - cardiovascular disorders - hypertension - urea - meta-analysis - antihypertensive agents - plant protein - animal protein - hart- en vaatziekten - bloeddruk - voedingseiwit - mortaliteit - hart- en vaatstoornissen - hypertensie - ureum - meta-analyse - antihypertensiva - plantaardig eiwit - dierlijk eiwit

Cardiovascular diseases (CVD) are the main cause of death worldwide. In 2012, about 17.5 million people died from CVD, accounting for 30% of all deaths. High blood pressure (BP) is a major cardiovascular risk factor, which was responsible for 10.4 million deaths in 2013. Diet and lifestyle play an important role in the etiology of hypertension. Maintenance of a desirable body weight, physical activity, and low intake of alcohol and salt are well-known measures to avoid high BP. Whether dietary protein, or more specifically plant and animal protein, could contribute to maintaining a healthy BP is less clear. The association between BP and CVD mortality has been extensively investigated. BP in prospective studies can be analyzed using different approaches, such as single BP (measured at one moment in time), single BP adjusted for regression dilution, average BP, and trajectories of BP. It is not yet clear which of these approaches is to be preferred for CVD risk prediction.

This thesis is centered on BP as a major cardiovascular risk factor. In the first part (Chapter 2, 3 and 4), the relation of dietary protein intake with BP level and change was examined. In the second part (Chapter 5 and 6), various approaches for analyzing repeated BP measurements were compared in relation to CVD and all‑cause mortality risk. The final chapter discusses the main findings and their implications.

Chapter 2 describes the association of 24-h urinary urea excretion, as a biomarker of total protein intake, with 9-year incidence of hypertension. We analyzed data of ~4000 men and women aged 28–75 years, who participated in the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, a prospective cohort study. BP was measured four times during 1997–2009 and participants were followed for hypertension incidence, defined as BP ≥140/90mmHg or use of antihypertensive medication. Urea excretion was assessed in two consecutive 24-h urine collections at baseline and approximately 4 years later, from which total protein intake was estimated. Protein intake based on 24-h urinary urea excretion was not associated with incident hypertension.

Chapter 3 presents findings for long-term total, animal and plant protein intake in relation to 5‑year BP change. Analyses were based on 702 observations of 272 men who participated in the Zutphen Elderly Study. Participants did not use antihypertensive medication and were initially free of CVD. Physical and dietary examinations were performed in 1985, 1990, 1995, and 2000. BP was measured twice at each examination and protein intake was assessed using the cross-check dietary history method. The upper tertiles of plant protein intake were associated with a mean 5‑year change in systolic BP of ‑2.9 mmHg (95% CI: ‑5.6, ‑0.2), compared with the bottom tertile. Total and animal protein intake was not associated with BP.

Chapter 4 describes a meta‑analysis of 12 observational studies and 17 randomized controlled trials (RCTs) of dietary protein, including animal and plant protein, in relation to BP. Protein intake in prospective cohort studies was not associated with incident hypertension. For RCTs that used carbohydrate as a control treatment, the pooled BP effect was ‑2.1 mmHg systolic (95% CI: ‑2.9, ‑1.4) for a weighted mean contrast in protein intake of 41 grams per day. There was no differential effect of animal and plant protein on BP.

Chapter 5 describes repeated BP measures and their association with CVD and all‑cause mortality and life years lost in two prospective and nearly extinct cohorts of middle-aged men, the Minnesota Business and Professional Men Study (n=261) and the Zutphen Study (n=632). BP was measured annually during 1947–1957 in Minnesota and 1960–1970 in Zutphen. After 10 years of BP measurements, men were followed until death on average 20 years later. Each 25-mmHg increase in average SBP was associated with a 49% to 72% greater CVD mortality risk, 34% to 46% greater all-cause mortality risk and 3 to 4 life years lost. Four systolic BP trajectories were identified, in which mean systolic BP increased by 5 to 49 mmHg in Minnesota and 5 to 20 mmHg in Zutphen between age 50 and 60. In Zutphen, a 2-times greater CVD and all-cause mortality risk and 4 life years lost were observed when comparing trajectories. In Minnesota, associations were twice as strong. BP trajectories were the strongest predictors of CVD mortality and life years lost in Minnesota men, whereas in Zutphen men, the average BP was superior to other measures.

Chapter 6 presents findings for average BP and BP trajectories in relation to CVD and all-cause mortality, taking into account antihypertensive medication. A total of 762 participants aged ≥50 years of the Rancho Bernardo Study were examined five times from 1984 to 2002 and monitored for cause‑specific mortality from 2002 to 2013. Each 20‑mmHg increment in average systolic BP was associated with 35% greater CVD mortality and 25% greater all-cause mortality risk. We identified four trajectories for systolic BP for which BP increases ranged from 5 to 12 mmHg between age 60 and 70. In individuals who belonged to the higher trajectories, 2‑3 times greater CVD mortality and 1.5-times greater all-cause mortality risks were observed, compared to those who belonged to the lowest trajectory. Long-term systolic BP trajectories and average systolic BP were both significant predictors of CVD and all-cause mortality. The associations were not modified by antihypertensive medication.

As described in Chapter 7, various approaches were used to study the relation between protein intake and BP. Findings from individual studies and a meta-analysis suggest that dietary protein per se does not affect BP within the range of intake generally consumed in the Netherlands. Replacing carbohydrates by protein, however, has a beneficial effect on BP.

Moreover, this thesis showed that BP trajectories are not superior to average BP in predicting CVD and all-cause mortality. A few repeated BP measurements, e.g. three or four, are likely to be sufficient for obtaining a reliable average BP and had a similar predictive value for mortality compared to BP trajectories. Therefore, average BP can be considered the most practical tool for estimating mortality risk.

Targeting persons with low socioeconomic status of different ethnic origins with lifestyle interventions : opportunities and effectiveness
Bukman, A.J. - \ 2016
Wageningen University. Promotor(en): Edith Feskens, co-promotor(en): Reint-Jan Renes. - Wageningen : Wageningen University - ISBN 9789462577022 - 169 p.
socioeconomic status - lifestyle - ethnic groups - intervention - cardiovascular diseases - type 2 diabetes - diabetes - obesity - dutch - turkish - glucose tolerance - morocco - physical activity - prevention - sociaal-economische positie - levensstijl - etnische groepen - interventie - hart- en vaatziekten - diabetes type 2 - suikerziekte - obesitas - nederlands - turks - glucosetolerantie - marokko - lichamelijke activiteit - preventie

Lifestyle intervention studies have shown that the development of cardiometabolic diseases can be partly prevented or postponed by the combination of a healthy diet and physical activity. Cardiometabolic diseases and their risk factors are particularly prevalent among individuals with low socioeconomic status and some ethnic minorities, and therefore these groups especially may benefit from participating in lifestyle interventions. Although individuals with low socioeconomic status and ethnic minorities could potentially benefit from lifestyle interventions, it seems that these groups are often not successfully reached for such interventions. Moreover, when they do participate in these interventions, they seem more likely to quit. The overall aim of this thesis was therefore to study opportunities for, and the effectiveness of, lifestyle interventions to reduce the risk of cardiometabolic diseases, targeting individuals with low socioeconomic status of different ethnic origins. To this end, this thesis reports two studies that identified opportunities for adapting lifestyle interventions to the target group’s needs, one study describing the process of adapting an effective lifestyle intervention (SLIM) into a new lifestyle intervention targeting individuals with low SES of different ethnic origins (MetSLIM) and two studies that determined the effectiveness of lifestyle interventions among the target group.

The aim of the study described in chapter 2 was to identify opportunities for adapting lifestyle interventions in such a way as to be more appealing for individuals with low socioeconomic status. The study provided insight into perspectives of groups with different socioeconomic positions regarding their current eating and physical activity behaviour; triggers for lifestyle change; and preferred ways to support lifestyle change. Data were gathered in semi-structured focus group interviews with adults with low socioeconomic status (four groups) and with adults with high socioeconomic status (five groups). In general, three key topics were identified, namely: current lifestyle is logical for participants given their personal situation; lifestyle change is prompted by feedback from their body; and support for lifestyle change should include individually tailored advice and could profit from involving others. The perceptions of the participants with low socioeconomic status were generally comparable to the perceptions shared by the participants with high socioeconomic status. Some perceptions were, however, especially mentioned in the low socioeconomic status groups. Participants with low socioeconomic status indicated that their current eating behaviour was sometimes affected by cost concerns. They seemed to be especially motivated to change their lifestyle when they experienced health complaints but were rather hesitant to change their lifestyle for preventive purposes. Regarding support for lifestyle change, participants with low socioeconomic status preferred to receive advice in a group rather than on their own. For physical activities, groups should preferably consist of persons of the same age, gender or physical condition.

The aim of the study described in chapter 3 was to identify how Turkish and Moroccan adults living in the Netherlands, aged 45 years and older, could be reached to participate in health checks for cardiometabolic diseases and follow-up (lifestyle) advice. In this study, questionnaire data were combined with interview data. This was done in order to use the narratives from the interviews to get a better understanding of the numbers that resulted from the questionnaire data. It turned out that both ethnic groups preferred an invitation from their general practitioner (GP) for a health check and preferred to fill out the health check questionnaire at the GP’s office or at home, on paper. They preferred to receive advice at individual level in relation to personal matters via either a physician or a specialised healthcare professional. Sixty-one percent of the Turkish respondents preferred to receive information in their native language, compared to 37% of the Moroccan respondents. Several participants mentioned a low proficiency in the local language as an explanation for their preference to fill out the health check questionnaire at home, to receive advice from an ethnicity-matched professional and to receive information in their native language. The results of this study suggested that the GP would be a promising contact to reach adults of Turkish and Moroccan origin for health checks or (lifestyle) advice. Furthermore, the findings suggested that it would be necessary to provide information in individuals’ native language to overcome language barriers and that (lifestyle) advice should be tailored towards the needs of the targeted individuals.

The insights gained into the needs and preferences of the target group – as described in chapter 2 and chapter 3 – were taken into account in the design of the MetSLIM intervention study. The MetSLIM study targeted individuals with low socioeconomic status of Dutch, Turkish and Moroccan origin. The MetSLIM study protocol was based on the SLIM study protocol. The SLIM study showed the beneficial effects of nutrition advice and physical activity promotion on the prevention type 2 diabetes, but drop-out was relatively high among low SES participants. Chapter 4 provides a detailed description of the development from the SLIM study protocol to the MetSLIM study protocol. Furthermore, this chapter gives insight into the obstacles encountered in developing the MetSLIM study to target individuals with low socioeconomic status of different ethnic origins. The new elements regarding the lifestyle intervention programme were: 1) additional group meetings about price concerns and social occasions with regard to a healthy diet; 2) ethnicity-matched dieticians; 3) gender-matched sports instructors; 4) all activities in the participants’ own neighbourhood; and 5) activities for women and men separately. The new elements regarding the study design, in order to study the effectiveness of the MetSLIM intervention programme, included: 1) from an university stetting to a community setting; 2) from a randomised controlled trial to a quasi-experimental study; 3) waist circumference – as a visible cardiometabolic risk factor – as main study outcome; 4) recruitment via GPs and in community centres; 5) translated study materials and ethnicity-matched research assistants involved in measuring; and 6) fewer measurements and measurements that could take place at different locations. Adaptations to the original SLIM study protocol were considered necessary in order to overcome practical barriers that hinder the target group’s participation; to suit the target group’s (cultural) needs; and to make it feasible to perform the study in a local (community) setting.

MetSLIM was not the only study set up based on the SLIM study. The SLIMMER study translated SLIM from a university setting to a real-world setting. The intervention was implemented in the public health and primary healthcare setting involving local GPs, practice nurses, dieticians, physiotherapists and sports clubs. The SLIMMER study did not target individuals with low socioeconomic status in particular; however, 52% of the study participants did have a low socioeconomic status, as determined by highest completed educational level. Chapter 5 describes how we explored the role of socioeconomic status in willingness to participate, programme attendance, programme acceptability, adherence to lifestyle guidelines, drop-out and effectiveness in the SLIMMER diabetes prevention intervention. The SLIMMER study was a randomised controlled trial, targeting 40- to 70-year-old adults at increased risk of type 2 diabetes, carried out in Apeldoorn and Doetinchem. The intervention group participated in a 10-month lifestyle programme: weekly training sessions were guided by a physiotherapist, and dietary advice was given by a dietician during 5–8 individual consultations and one group session. Measurements were carried out at baseline, after 12 months and six months after the active intervention period ended. The study showed that participation, attendance, acceptability, adherence, drop-out and effect of the SLIMMER study were mostly not affected by socioeconomic status. The SLIMMER study was able to reach the low socioeconomic status group as effectively as the higher socioeconomic status group, resulting in at least similar health benefits. The SLIMMER sample size was too small to study differences within the low socioeconomic status group, e.g. comparing the low vs. the least educated or comparing ethnic groups. Only 10% of the 316 SLIMMER participants had the lowest educational levels (no education or primary education) and only 11% had a foreign background.

The aim of the study described in chapter 6 was to measure the effectiveness of the MetSLIM intervention on waist circumference and other cardiometabolic risk factors, lifestyle and quality of life among 30- to 70-year-old adults with an elevated waist-to-height ratio. In the MetSLIM study, 220 individuals participated, of whom 40% had no education or only primary education and of whom 64% had a foreign background. MetSLIM had a quasi-experimental design with measurements at baseline and after 12 months. Participants were recruited in deprived neighbourhoods of Arnhem and Eindhoven via either their GP or in community centres. The intervention group participated in a 12-month lifestyle programme: an introductory group meeting was guided by the researcher, weekly physical activity lessons were guided by a sports instructor and dietary advice was given by an ethnicity-matched dietician (in total four hours of individual consultations and three group sessions). The study showed that the MetSLIM lifestyle intervention was effective in reducing waist circumference, other measures of obesity, total and LDL cholesterol, and quality of life. MetSLIM had a drop-out of 31%, which was higher than at 12 months in the SLIM study (10%) and SLIMMER study (13%), but comparable to drop-out in similar studies among ethnic minorities or low socioeconomic status populations.

Finally, in chapter 7, the main results of this thesis are described, followed by a discussion of methodological considerations, public health implications, suggestions for future research and the general conclusion. The adaptation process from SLIM to MetSLIM is discussed, including a reflection on the decision to use SLIM as a starting point and the decision to target three different ethnic groups at the same time. Moreover, difficulties in defining and selecting persons with low socioeconomic status and specific ethnic groups within research are addressed. As SLIMMER and MetSLIM proved that low socioeconomic status populations can be reached, and that their health can be improved when they participate in lifestyle interventions, it is suggested that further implementation should be considered. Insight should be gained into the ‘black box’ of lifestyle interventions; i.e. we should get to know what works for whom. Planned future research includes a process and economic evaluation of MetSLIM.

This thesis has shown that intensive combined lifestyle interventions can be effective in low socioeconomic status populations and identified possible adaptations to make lifestyle interventions more suitable for individuals with low socioeconomic status of Dutch, Turkish and Moroccan origin. The question is not whether a lifestyle intervention can be effective, but how diverse groups can be reached and benefit from it. For this purpose, further insight into the success of different adaptations for different target groups should be obtained to reveal the effective elements to reach, inspire and retain different low socioeconomic status populations and ethnic minorities with lifestyle interventions.

Bone marrow-specific caspase-1/11 deficiency inhibits atherosclerosis development in Ldlr-/- mice
Hendrikx, Tim ; Jeurissen, M.L.J. ; Gorp, P.J. Van; Gijbels, M.J. ; Walenbergh, S.M.A. ; Houben, Tom ; Gorp, Rick Van; Pöttgens, C.C. ; Stienstra, Rinke ; Netea, M.G. ; Hofker, M.H. ; Donners, M.M.P.C. ; Shiri-Sverdlov, Ronit - \ 2015
FEBS Journal 282 (2015)12. - ISSN 1742-464X - p. 2327 - 2338.
atherosclerosis - cardiovascular diseases - caspase-1/11 - inflammasome - macrophage

Recent investigations have suggested that inflammasome activation plays an important role during atherosclerosis. Upon activation, the inflammasome induces processing and release of pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18) via activation of caspase-1/11. Previously, it was shown that complete caspase-1 deficiency is protective against atherosclerosis development. However, while macrophages are the main inflammatory cells involved in atherosclerosis, the exact role of macrophage-specific caspase-1/11 activation during development of cardiovascular disease has never been investigated. We hypothesized that hematopoietic caspase-1/11 deficiency leads to reduced atherosclerosis development. To investigate the specific contribution of hematopoietic caspase-1/11 activation to atherosclerosis development, Ldlr-/- mice received a transplant (tp) of wild-type (WT) or caspase-1/11-/- bone marrow, to create WT-tp mice and caspase-1/11-/--tp mice, and fed a high-fat, high-cholesterol diet for 12 weeks. Our results showed an increase in anti-inflammatory blood leukocytes in caspase-1/11-/--tp mice compared with WT-tp mice, as indicated by a decreased level of Ly6Chigh monocytes and an increased level of Ly6Clow monocytes. In line with our hypothesis, hematopoietic deletion of caspase-1/11 resulted in a strong reduction in atherosclerotic plaque size. Furthermore, necrotic core content was dramatically decreased in caspase-1/11-/--tp mice. Our data indicate that hematopoietic caspase-1/11 activation is involved in vascular inflammation and atherosclerosis, and plays an important role in cardiovascular disease progression. In this study, we investigated the contribution of hematopoietic caspase-1/11 to atherosclerosis development by transferring wild-type or caspase-1/11 deficient bone marrow cells into hyperlipidemic Ldlr-/- recipient mice. Hematopoietic deletion of caspase-1/11 resulted in smaller plaque size and reduced cell death in the plaque area compared to controls. These data indicate that hematopoietic caspase-1/11 activation plays an important role in vascular inflammation and atherosclerosis.

Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality
Sijtsma, F.P.C. - \ 2015
Wageningen University. Promotor(en): Daan Kromhout; D.R. Jacobs, co-promotor(en): Sabita Soedamah-Muthu. - Wageningen : Wageningen University - ISBN 9789462575493 - 207
dieet - hart- en vaatziekten - atherosclerose - prognostische merkers - ziektemerkers - mortaliteit - classificatiesystemen - epidemiologie - longitudinaal onderzoek - diet - cardiovascular diseases - atherosclerosis - prognostic markers - disease markers - mortality - classification systems - epidemiology - longitudinal studies

Summary belonging to the thesis entitled ‘Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality’

The long history of epidemiologic studies on diet and cardiovascular disease (CVD) has traditionally relied on analysis of specific nutrients or foods. Dietary patterns are multiple dietary components operationalized as a single exposure; they reflect the entire diet. In general, two methods are used to define dietary patterns: 1) theoretically, or a priori, defined dietary scores and 2) empirically, or a posteriori, derived dietary patterns. A priori dietary scores were developed to assess diet quality based on adherence to dietary patterns or recommendations. An example of an ‘a posteriori’ approach is factor analysis (e.g. principal components analysis (PCA)). Factor analysis reduces data into patterns based upon intercorrelations between nutrients or foods. The aim of this thesis was to create, examine and compare several dietary patterns and indices and assess these in relation to both early stage markers of CVD (markers of endothelial function and oxidative stress) and to mortality from CVD and all-causes.

In chapter 2 we described the creation of the A Priori Diet Quality Score, representing overall diet quality in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The CARDIA study included 5115 black and white men and women, aged 18-30 at baseline (1985-86). Diet was assessed diet at baseline, year 7(1992-93) and 20 (2005-06) examinations. The A Priori Diet Quality Score summed 46 food groups rated by investigators as positive or negative on the basis of hypothesized health effects. In 2652 participants with 3 diet assessments, the mean (±SD) A Priori Diet Quality Score increased from 64.1± 13.0 at year 0 to 71.1 ± 12.6 at year 20, which was primarily attributable to increased age. However, the secular trend, which was estimated from differences of dietary quality scores across time at a fixed age (age matched time trend), decreased. The diet score was higher in whites than in blacks and in women than in men and increased with education, but demographic gaps in the score narrowed over 20 y. Consumption of positively rated food groups tended to increase and negatively rated food groups tended to decrease, and were similar in direction across demographic groups.

In chapter 3 we used the ‘A Priori Diet Quality Score’ and two dietary patterns derived using principal components analysis (PCA) the ‘Fruit and Vegetables’ dietary pattern and the ‘Meat’ dietary pattern in the CARDIA study. We studied prospective associations of the ‘A Priori Diet Quality Score’, the ‘Fruit and Vegetables’ dietary pattern and the ‘Meat’ dietary pattern with cellular adhesion molecules (CAMs). The ‘Fruit and Vegetables’ dietary pattern was characterized by high intakes of fruit, vegetables, and whole grains and the ‘Meat’ dietary pattern by high intakes of red meat, refined grain, and butter. The ‘A Priori Diet Quality Score’ was related to all CAMs. The ‘Fruit and Vegetables’ dietary pattern was related to E-selectin and sICAM-1 but not to P-selectin and VCAM. The ‘Meat’ dietary pattern was related to all CAMs except VCAM. Strongest associations were for the ‘Meat’ dietary pattern with E-selectin (effect size 28% of an SD (+3.9/13.7 ng/mL)) and P-selectin (effect size 37% of an SD (+4.1/11.2 ng/mL)) and the ‘A Priori Diet Quality Score’ with sICAM-1 (effect size 34% of an SD (-15.1/44.7 ng/mL)) and VCAM (effect size of 26% of an SD (-45.1/170.3 ng/mL)).

Chapter 4 described prospective associations of the A Priori Diet Quality Score, ‘Fruit and Vegetables’ dietary pattern and ‘Meat’ dietary pattern and a plasma biomarker of lipid peroxidation, F2-isoprostanes also in the CARDIA study. We estimated associations between each dietary pattern and plasma F2-isoprostanes cross-sectionally (at year 20, n=2736) and prospectively (year 0/7 average diet and year 15/20 average F2-isoprostanes, n=2718). In the cross-sectional analysis, the A Priori Diet Quality Score and the ‘Fruit and Vegetables’ dietary pattern were inversely, and the ‘Meat’ dietary pattern was positively, associated with F2-isoprostanes (all p values <0.001). These associations were also statistically significant in prospective analysis.

In chapter 5 we described a food classification system derived from the Food-based Dietary Guidelines in the Netherlands that can be used to systematically and objectively classify foods in relation to their effects on health. Classification criteria for each food group were developed based on presumed positive, neutral or negative effects on chronic diseases of five nutrients: four that likely increase (saturated fatty acids, mono-trans unsaturated fatty acids, sodium, and added sugar) and one that likely decreases (dietary fiber) the risk of chronic diseases. This classification system also provided a framework to create food-based dietary scores for epidemiologic research on diet and chronic disease relationships.

Chapter 6 describes the creation of two dietary scores the ‘Dutch Healthy Nutrient and Food Score’ and the ‘Dutch Undesirable Nutrient and Food Score’ based on the food classification system described in chapter 5 in the Alpha Omega Trial. The Alpha Omega Trial is a randomized controlled trial; however the current analyses were done from an observational prospective cohort perspective (with adjustment for intervention groups). We included 4307 cardiac patients aged 60-80 years and monitored mortality for 10 years. Patients in the highest quintile of the ‘Dutch Healthy Nutrient and Food Score’ had 30% (HR 0.70; 95% CI 0.55-0.91) lower CVD and 32% (HR 0.68; 95%CI 0.47-0.99) lower all-cause mortality risk compared to patients in the first quintile. The ‘Dutch Undesirable Nutrient and Food Score’ was unrelated to both CVD and all-cause mortality.

In Chapter 7 we also created a ‘Dutch Healthy Nutrient and Food Score’ and a ‘Dutch Undesirable Nutrient and Food Score’ in the Zutphen Elderly Study. We assessed the association of these scores with 25 year CVD and all-cause mortality and life-years gained. We divided the men (age 65-84 years) into those with (n=210) and without (n=616) cardiovascular-metabolic diseases at baseline in 1985. During a median follow-up of 10.6 years (IQR 5.8-15.9) 806 participants died, of whom 359 from CVD. Diet scores did not predict death in all men. Among men with cardiovascular-metabolic diseases, ‘Dutch Healthy Nutrient and Food Score’ was associated with lower CVD (HR: 0.57; 95%CI: 0.35-0.93) and all-cause mortality risk (HR: 0.64; 95% CI: 0.44-0.94) comparing highest vs. lowest tertiles of the score. Men with cardiovascular-metabolic diseases in the highest vs. lowest tertile of the ‘Dutch Healthy Nutrient and Food Score’ lived 2.5 year longer. The ‘Dutch Healthy Nutrient and Food Score’ was not associated with CVD and all-cause mortality in men without cardiovascular-metabolic diseases. The ‘Dutch Undesirable Nutrient and Food Score’ was not associated with any of the outcomes.

In Chapter 8 we summarized the main findings of this thesis and reflected on some methodological considerations. First, we discussed the different approaches to derive dietary scores and patterns and the advantages and disadvantages of these methods. Second, we reflected on important aspects for creating a priori dietary scores and on further research. Finally, the general conclusions and implications were presented.

From the results presented in this thesis we conclude that adherence to a healthy diet is inversely associated with early stage markers of CVD (markers of endothelial function and oxidative stress), CVD and all-cause mortality. In summary, a healthy diet consists of plenty of vegetables and fruit, legumes, whole grains, nuts and seeds, moderate intake of fish/poultry/lean meats and low fat dairy, and limited intake of processed meats, refined grains, sugar sweetened beverages, ready meals and snacks. However, this thesis also showed that a high quality dietary pattern can be achieved in several different ways, and may differ among populations.

Public health impact of salt reduction
Hendriksen, M.A.H. - \ 2015
Wageningen University. Promotor(en): Hendriek Boshuizen, co-promotor(en): Joop van Raaij; Marianne Geleijnse. - Wageningen - ISBN 9789462575462 - 223
zout - jodiumhoudend zout - opname (intake) - reductie - gezondheid - voeding en gezondheid - modelleren - hart- en vaatziekten - hypertensie - europa - salt - iodized salt - intake - reduction - health - nutrition and health - modeling - cardiovascular diseases - hypertension - europe

The health and economic burden related to cardiovascular diseases is substantial and prevention of these diseases remains a challenge. There is convincing evidence that high salt intake affects blood pressure and the risk of cardiovascular diseases. As salt intake is far above the recommended maximum level of intake, salt reduction may help to reduce cardiovascular disease incidence. However, the effect of salt reduction initiatives on intake levels and long-term health is largely unknown. The main aim of the research described in this thesis is to assess salt intake and the potential health impact of salt reduction in the Netherlands and in Europe. This is addressed by estimating the potential effect of salt reduction strategies on salt intake, by monitoring the effect of the ongoing salt reduction initiatives in the Netherlands between 2006 and 2010 on daily salt intake and by projecting the expected long-term health benefits of salt reduction in the Netherlands and Europe.

Firstly, we used data from the Dutch National Food Consumption Survey 2007-2010 and the Dutch Food Composition Database 2010 to study the effect of two potential salt reduction scenarios on salt intake from processed foods. In the first scenario, sodium levels in processed foods were reduced towards their minimum feasible sodium level. In the second scenario, foods were substituted by a low-salt alternative within the same food category. This study demonstrated that daily salt intake from foods could be reduced below the recommended maximum intake of 6 g/d, provided these strategies are successfully implemented.

Secondly, the effect of the ongoing salt reduction initiatives in the Netherlands between 2006 and 2010 was evaluated. Dutch adults in two cross-sectional studies (n=317 in 2006 and n=342 in 2010) collected a single 24h urine sample. Despite the initiatives of the food industry to reduce sodium levels in processed foods, no statistically significant difference in daily salt intake was observed between 2006 (8.7 g/d) and 2010 (8.5 g/d).

Thirdly, the long-term health impact of salt reduction was assessed for the Netherlands using the RIVM Chronic Disease Model and for Europe using the Dynamic Model for Health Impact Assessment (DYNAMO-HIA). A two-step approach was used: the effect of salt reduction on blood pressure was estimated, which was subsequently translated into occurrence of cardiovascular diseases. Substantial changes in incident stroke (6.0%) and acute myocardial infarction (4.4%) can be expected in the Netherlands if sodium contents in processed foods were reduced to the minimum feasible level. The potential health impact of population-wide adherence to the salt intake guideline of the World Health Organization (maximum of 5 g/d) ranged for nine European countries between 10.1% in Finland to 23.1% in Poland for stroke, and between 6.6% in Finland to 15.5% in Poland for ischemic heart diseases.

Finally, a methodological comparison of seven population health models on salt reduction revealed that these models vary in underlying assumptions. We demonstrated that these differences in assumptions may substantially affect the health impact estimates.

In conclusion, technologically feasible salt reductions in processed foods or changes in dietary behaviour may, if implemented successfully, lead to a substantial lowering of daily salt intake, and thereby contribute to considerable health gain. Cross-country comparisons of health impact of salt reduction strategies might benefit from more transparency on the necessary assumptions in the various population health impact models for salt reduction used worldwide.

Dietary proteins and aspects of the metabolic syndrome : evidence from observational studies and short-term interventions
Nielen, M. van - \ 2015
Wageningen University. Promotor(en): Edith Feskens, co-promotor(en): Marco Mensink. - Wageningen : Wageningen University - ISBN 9789462574793 - 131
metabool syndroom - diabetes mellitus - stofwisselingsstoornissen - diabetes type 2 - hart- en vaatziekten - sojaeiwit - arginine - eiwitinname - ziekte-incidentie - ontsteking - cohortstudies - metabolic syndrome - metabolic disorders - type 2 diabetes - cardiovascular diseases - soya protein - protein intake - disease incidence - inflammation - cohort studies

Background Type 2 diabetes (T2D) and cardiovascular diseases (CVD) are important causes of morbidity and mortality worldwide. The metabolic syndrome (MetS) identifies people at elevated risk of T2D and CVD by its mutual risk factors, such as abdominal obesity, atherogenic dyslipidemia, raised blood pressure and impaired glucose tolerance. Improvements in individual aspects of MetS could be risk-reducing for T2D and CVD and could thus be clinically relevant. Besides by using drug therapy, this can be achieved by lifestyle changes, such as weight loss, increasing physical activity and changes in dietary composition. In addition to general dietary recommendations, such as diets rich in fiber, fruits and vegetables and low in refined grains and saturated fatty acids, increasing dietary protein and soy intake seem promising approaches to prevent MetS. Short-term trials report positive effects of dietary protein intake on weight loss and weight maintenance after weight loss. The postprandial and short-term effect of protein and soy consumption on insulin resistance, glucose homeostasis, and other aspects of MetS are not frequently studied in humans in energy balance. Also, the long-term association between dietary protein intake and T2D incidence is uncertain, it even seemed risk-increasing in prior research.

Objectives We evaluated the impact of dietary protein intake on T2D incidence, aspects of MetS and other cardio-metabolic risk factors, by observational studies (long-term) and interventions (short-term). We studied not only total protein intake, but also specific protein types, more specifically soy protein and arginine-rich protein. We explored the long-term association between total, animal, and plant protein intake and the incidence of T2D. We further investigated the effects of a 4-week strictly controlled weight-maintaining moderate-high-protein diet rich in soy on insulin sensitivity and other cardio-metabolic risk factors. Next, we investigated if inflammatory markers were also changed as a possible pathway through which dietary protein affects cardio-metabolic risk factors. Lastly, we examined whether protein, and more specific arginine-rich protein, added to a high fat meal improved postprandial metabolism and cardiovascular risk factors.

Methods The association between dietary protein intake and T2D incidence was studied in the EPIC-InterAct case-cohort study (nincident cases= 12,403; nsubcohort=16,154).

In a randomized crossover trial of 2 4-week periods diets with a moderate-high-protein content, i.e. 22 energy percent (En%) protein, 27En% fat, and 50En% carbohydrate, were studied (n=15). In a diet with protein from mixed sources (HPmix) we partly replaced meat products with soy products (HPsoy) to investigate the effect of soy protein intake on insulin resistance, glucose homeostasis, and other aspects of MetS.

A high-fat challenge test was used to study postprandial metabolic markers, inflammatory markers and arterial stiffness (n=18). We compared the postprandial response after a high-fat liquid control meal (95g fat) without protein with meals with 30g added protein.

Results Intake of total protein (per 10 g: HR 1.06 [95% CI 1.02–1.09], Ptrend < 0.001) and animal protein (per 10 g: HR 1.05 [95% CI 1.02–1.08], Ptrend < 0.001) was associated with higher incidence of T2D, after adjustment for main confounders including other dietary factors.

Partly replacing meat with soy in a moderate-high-protein diet resulted in greater insulin sensitivity (FSIGT: SI:34 ± 29 vs. 22 ± 17 (mU/L)-1min-1, P=0.048; disposition index:4974 ± 2543 vs. 2899 ± 1878, P=0.038). After HPsoy total cholesterol was 4% lower than after HPmix (4.9 ± 0.7 vs. 5.1 ± 0.6 mmol/L, P=0.001) and LDL cholesterol was 9% lower (2.9 ± 0.7 vs. 3.2 ± 0.6 mmol/L, P=0.004). The summary score for inflammation was lower after HPsoy compared with HPmix (ɀ-score: -0.2 ± 0.3 vs. -0.1 ± 0.2, P=0.04), after excluding participants with CRP>6mg/L and extreme outliers. Individual inflammatory markers were not significantly different.

Adding protein to a high-fat meal increased the postprandial insulin response. No differences between arginine-rich and protein low in arginine on postprandial responses were seen. Intact proteins and hydrolysates resulted in similar responses.

Conclusion High total and animal protein intake was associated with modestly elevated T2D incidence in a large cohort of European adults. In contrast, a moderate-high-protein diet for 4 weeks improved many cardio-metabolic risk factors. Partly replacing meat with soy in this moderate-high-protein diet had clear advantages regarding insulin sensitivity and total and LDL cholesterol, and it improved the overall inflammatory state, although not showing clear benefits at individual inflammation markers. We hypothesized to see an origin of these short-term health effects in postprandial properties of arginine-rich protein. However, arginine-rich protein was not superior to a protein low in arginine added to a high-fat meal, regarding postprandial excursions in glucose, insulin, lipids and inflammatory markers.

In view of the rapidly increasing prevalence of MetS and T2D, limiting iso-energetic diets high in dietary proteins, particularly from animal sources, should be considered as on the long-term protein intake seems to increase T2D and CVD risk. However, at the short-term partly replacing meat with soy in a moderate high-protein diet could be preventive for several aspects of MetS, such as improvements in insulin sensitivity, total and LDL cholesterol and possibly a reduced inflammatory state.

Young children and obesity : development and evaluation of familiy-oriented treatment
Hoek, E. van - \ 2015
Wageningen University. Promotor(en): Edith Feskens, co-promotor(en): A.J. Janse; Laura Bouwman. - Wageningen : Wageningen University - ISBN 9789462574540 - 182
obesitas - overgewicht - kinderen - peuters en kleuters - pediatrie - behandeling - kinderziekten - medische behandeling - lichaamssamenstelling - kwaliteit van het leven - vetweefsel - hart- en vaatziekten - kwantitatieve methoden - voeding en gezondheid - obesity - overweight - children - preschool children - paediatrics - treatment - childhood diseases - medical treatment - body composition - quality of life - adipose tissue - cardiovascular diseases - quantitative methods - nutrition and health

Thesis: Young Children and Obesity – Development and Evaluation of Family-oriented Treatment, Esther van Hoek

Introduction

The prevalence of childhood obesity has increased rapidly during the last decades. Childhood obesity is a multisystem disease with serious consequences such as hypertension, dyslipidemia, chronic inflammation, endothelial dysfunction and hyperinsulinemia. In addition, obese children have a decreased health-related quality of life (HRQoL).

The age interval of 3 to 7 years is a critical growth period. Fast increase of weight in this period is associated with obesity later in life. Furthermore, starting treatment at younger age is associated with a larger reduction in overweight. At the start of this project in 2009, there was no evaluated treatment program available for young obese children (defined as 3 to 8 years).

The risk of cardiovascular diseases and type 2 diabetes (i.e. cardiometabolic risk) can be assessed by measuring conventional risk factors (for example blood pressure). Other markers, such as pro-inflammatory markers, are part of the cardiometabolic risk profile. Epicardial adipose tissue is a metabolically active cardiac fat depot. In obese adults, the epicardial adipose tissue thickness (EATT) is increased, this is correlated to atherosclerosis. It is unknown whether young overweight children have already increased EATT.

The aim of this thesis is to develop, implement and evaluate a treatment program for obese young children. Furthermore, it aims to assess whether EATT is increased in obese young children and is correlated with the cardiometabolic risk profile, and with treatment.

Methods

The treatment program for obese young children is developed based on a review of the clinical guidelines, a literature review (including a systematic review with meta-analysis and an extended literature review) and target group interviews. The findings were integrated with professional judgement. To evaluate the resulting program called AanTafel!, a pilot study was performed (n=7 children), including a process evaluation based on parental interviews and questionnaires with the therapists. The effectiveness of AanTafel! was evaluated with a pre-post-test design including 40 children with a median BMI z-score of 3.4 (standard deviation 1.0) in secondary care. The BMI-z-score was the main outcome measure. Secondary outcome measures were components of the metabolic syndrome, markers of cardiometabolic risk, and HRQoL. Outcome measures were assessed at baseline and at the end of treatment (1 year). The BMI z-score was also evaluated 3 years after baseline in the first 23 children who finished treatment. EATT was measured by echocardiography in 25 obese, 8 overweight, and 15 normal weight young children. In the obese and overweight children the EATT, as well as cardiometabolic risk factors, and the markers adiponectin and high sensitive CRP (hsCRP) were measured at baseline and after treatment.

Results

Meta-analysis showed that multicomponent treatment programs of moderate or high intensity (> 26 hours) were the most effective and resulted in a decrease of BMI z-score of 0.5. During the development of the treatment program, the gaps in evidence in clinical guidelines for childhood obesity treatment were overcome by insights from an additional literature review, target group interviews and professional judgement. The resulting treatment program AanTafel! has the following key characteristics: multicomponent, multidisciplinary, family-based with focus on parents, age-specific, tailored to individual children and families, a duration of one year and a combination of individual and group sessions and a web-based learning module. The pilot study showed that to improve parental involvement, peer support, family tailoring, and highly participative elements (such as self-monitoring) are important. The treatment program AanTafel! resulted in a change of mean BMI z-score of -0.5 directly after finishing treatment. This clinical relevant result persisted 2 years after baseline. Furthermore, a significant increase in HDL cholesterol and a reduction in the number of components of metabolic syndrome were found. Regarding markers of cardiometabolic risk, an overall significant decrease was seen in IL18, e-selectin, and sICAM. The HRQoL showed a non-significant improvement in most domains, with a clinically relevant improvement in the physical summary score. EATT was higher in overweight and obese young children compared to their normal weight peers. EATT was inversely correlated with adiponectin, but correlations with other cardiometabolic risk factors were not statistically significant. EATT did not change during treatment (n=17).

Conclusion

During the development process of an obesity treatment program, it was important to add the views of the target group and therapists to the evidence from clinical guidelines and literature review. The resulting treatment program AanTafel! is effective with a clinically relevant decrease of BMI z-score, an improvement of cardiometabolic risk profile, and a clinically relevant increase in the physical summary score of HRQoL. EATT is increased in obese young children; this is inversely correlated with adiponectin.

Of fats and foods
Kromhout, D. - \ 2015
Wageningen : Wageningen UR, Wageningen - ISBN 9789462571983 - 24
nutrition and health - heart diseases - cardiovascular diseases - fatty acids - cholesterol - disease prevention - food consumption - risk factors - public health - human nutrition research - voeding en gezondheid - hartziekten - hart- en vaatziekten - vetzuren - ziektepreventie - voedselconsumptie - risicofactoren - volksgezondheid - voedingsonderzoek bij de mens
Farewell address upon retiring as Professor of Public Health Research at Wageningen University on 16 April 2015
Unravelling mechanisms of dietary flavonoid-mediated health effects: effects on lipid metabolism and genotoxicity
Hoek-van den Hil, E.F. - \ 2015
Wageningen University. Promotor(en): Ivonne Rietjens; Jaap Keijer, co-promotor(en): Peter Hollman. - Wageningen : Wageningen University - ISBN 9789462573031 - 157
flavanoïden - flavonoïden - vetzuren - quercetine - flavonolen - lichaamsgewicht - lipidenmetabolisme - hart- en vaatziekten - lever - vetweefsel - gezondheid - genotoxiciteit - voeding - muizen - flavanoids - flavonoids - fatty acids - quercetin - flavonols - body weight - lipid metabolism - cardiovascular diseases - liver - adipose tissue - health - genotoxicity - nutrition - mice

Summary

Consumption of foods containing flavonoids is associated with a reduced risk of cardiovascular diseases (CVD), possibly by lipid-lowering effects. On the other hand, for one of these flavonoids, quercetin, also genotoxicity was shown especially in in vitro bioassays. Therefore, the first aim of this thesis was to identify mechanisms underlying potential beneficial health effects of flavonoids. The focus was on hepatic lipid metabolism and circulating lipids and a molecular and physiological approach was used. Secondly, we aimed to study the potential in vivo genotoxic effects of quercetin by transcriptome analyses in liver and small intestine, since these represent the tissues of first contact exposed to relatively high levels upon oral intake of flavonoids.

Circulating lipids are important CVD-related risk markers, which are in general determined with commercially available enzyme-based assays. However, the usual enzyme in these assays, peroxidase, has previously been reported to be inhibited by flavonoids. Therefore, we have studied in chapter 2 whether these assays can adequately be used in flavonoid research. We observed that various flavonoid aglycones interfere with peroxidase used in triglycerides (TG) and free fatty acids (FFA) enzymatic assays, reporting incorrect lower TG and FFA levels than actually present. Furthermore, addition of metabolites such as isorhamnetin or quercetin-3-O-glucuronide, the major metabolite of quercetin in human and rat plasma, to murine serum also resulted in a significant reduction of the detected TG levels, while a trend was seen towards reduced FFA levels. It can be concluded that when applying these biochemical assays, vigilance is needed and alternative analytical methods assessing FFA or TG levels should preferably be applied for studying the biological effects of flavonoids on TG and FFA levels.

In chapter 3 mechanistic and physiological effects of quercetin on hepatic lipid metabolism were studied. C57BL/6JOlaHsd male adult mice received a mild high-fat (30 en%) diet without or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H-NMR were used to quantitatively measure serum lipid profiles. Whole genome microarray analysis of liver tissue was used to identify potential mechanisms underlying altered circulating lipid levels by quercetin supplementation. Body weight, energy intake and hepatic lipid accumulation did not differ significantly between the quercetin and the control group. In serum of quercetin-fed mice, TG levels were decreased by 14% (p<0.001) and total poly unsaturated fatty acids (PUFA) levels were increased by 13% (p<0.01). Levels of palmitic acid, oleic acid, and linoleic acid were all decreased by 9-15% (p<0.05) in quercetin-fed mice. Both palmitic acid and oleic acid can be oxidized by omega-oxidation. Gene expression profiling showed indeed that quercetin increased hepatic lipid metabolism, especially omega-oxidation. At the gene level, this was reflected by the up-regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450 activities) and the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3) were also up- regulated in the quercetin-fed mice. We concluded that quercetin intake increased hepatic lipid omega-oxidation and lowered corresponding circulating lipid levels, which may contribute to potential beneficial effects of quercetin on CVD.

Subsequently, in chapter 4 effects of quercetin supplementation were studied in mice given a high-fat (40 en%) background diet. The set-up of the experiment was the same as in chapter 3, with the exception of the background diet that was used, which was different in fat content and composition. This high-fat diet-induced body weight gain, and serum and hepatic lipid accumulation, which are all known risk factors for CVD. The aim of this study was to investigate the effects and underlying molecular mechanisms of the effects of the flavonoid quercetin on hepatic lipid metabolism in mice given this high-fat diet background. C57BL/6JOlaHsd male adult mice received the high-fat diet without or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Body weight gain was 29% lower in quercetin fed mice versus control mice (p<0.01), while the energy intake was not significantly different. Quercetin supplementation lowered high-fat diet-induced hepatic lipid accumulation to 29% of the amount present in the control mice (p<0.01). 1H-NMR serum lipid profiling revealed that the supplementation also significantly lowered high-fat diet-induced increases in serum lipid levels. Global gene expression profiling of liver showed that cytochrome P450 2b (Cyp2b) genes, key target genes of the transcription factor Car, were down-regulated. However, the induction of omega-oxidation observed by quercetin supplementation to a mild high-fat (30en%) diet (chapter 3), was not observed this time with the high-fat (40en%) diet. Cumulatively, quercetin decreased high-fat diet-induced body weight gain, hepatic lipid accumulation and serum lipid levels. This was accompanied by regulation of cytochrome P450 2b genes in liver, which are considered to be under transcriptional control of CAR. The quercetin effects are likely dependent on the fat content and composition of the diet.

In chapter 5 we investigated whether flavonoids from other flavonoid subclasses can exert the same effects as we observed for quercetin. Effects of quercetin, hesperetin, epicatechin, apigenin and anthocyanins, in C57BL/6JOlaHsd male adult mice fed a high-fat diet for 12 weeks were compared, relative to a normal-fat diet. High-fat diet-induced body weight gain was significantly lowered by all flavonoids (17-29%), but most by quercetin. Quercetin significantly lowered high-fat diet-induced hepatic lipid accumulation (by 71%). High-fat diet-induced increases of mesenteric adipose tissue weight and serum leptin levels were significantly lowered by quercetin, hesperetin, and anthocyanins. Adipocyte cell size and adipose tissue inflammation were not affected.

The effects on body weight and adiposity could not be explained by individual significant differences in energy intake, energy expenditure, nor by differences in activity. Lipid metabolism was not changed as measured by indirect calorimetry or expression of known lipid metabolic genes in liver and white adipose tissue. Hepatic expression of Cyp2b9 was strongly down-regulated by all flavonoids. Overall, all five flavonoids lowered parameters of high-fat diet-induced adiposity, with quercetin being most effective.

Next to the beneficial health effects of flavonoids, the safety of flavonoids is under discussion, mainly because of potential genotoxic effects found for quercetin in vitro. Therefore, in chapter 6 the in vivo genotoxicity of this flavonoid was studied by transcriptome analyses in two tissues, small intestine and liver, where the highest exposure to quercetin is expected. This is especially of interest in view of high intake by widely available food supplements. Quercetin (0.33%) supplemented to a high-fat diet was administered to C57BL/6JOlaHsd male adult mice during 12 weeks. Serum alanine aminotransferase and aspartate aminotransferase levels revealed no indications for hepatotoxicity. General microarray pathway analysis of liver and small intestinal tissue samples showed no regulation of genotoxicity related pathways. In addition, analysis of DNA damage pathways in these tissues did also not point at genotoxicity. Furthermore, comparison with a published classifier set of transcripts for identifying genotoxic compounds did not reveal any similarities in the regulation of these classifier set by quercetin. Available microarray datasets of known genotoxic liver carcinogens, 2-acetylaminofluorene and aflatoxin B1 in mice were taken along as positive controls for comparison, and indeed showed genotoxic properties (regulation of genotoxic related genes) in the analyses. This transcriptomic analysis showed that supplementation with quercetin at ~350 mg/kg bw/day for 12 weeks did not induce genotoxicity in liver and small intestine.

In conclusion, we have shown in vivo efficacy of flavonoids reflected by effects on metabolic health parameters, including hepatic lipid metabolism. These effects on hepatic lipid metabolism seemed to be related or influenced by the transcription factor CAR. The dietary contexts appeared to modify the health effects. The five studied flavonoids in general showed the same effects, with quercetin being the most effective. No genotoxicity of quercetin was found by transcriptome analyses in liver and small intestine. Overall, we have obtained indications for beneficial health effects of flavonoids in mice, which makes it interesting to study if these effects can be extrapolated to humans to further explore their potential as functional compounds of dietary flavonoid intake.

Phytosterols and blood lipid risk factors for cardiovascular disease
Ras, R.T. - \ 2014
Wageningen University. Promotor(en): Frans Kok, co-promotor(en): Marianne Geleijnse; P.L. Zock. - Wageningen : Wageningen University - ISBN 9789462571006 - 234
hart- en vaatziekten - hart- en vaatstoornissen - phytosterolen - sterolen - bloedvetten - risicofactoren - cholesterol - cardiovascular diseases - cardiovascular disorders - phytosterols - sterols - blood lipids - risk factors

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Lifestyle improvements including dietary changes are important for CVD prevention. This thesis aimed to advance insights in the role of phytosterols, lipid-like compounds present in foods or plant origin, in the management of blood lipid risk factors for CVD. Phytosterols include plant sterols and their saturated form, plant stanols. These compounds resemble cholesterol in both structure and function, but cannot be produced by the human body. The intake of phytosterols occurs through plant-based foods and/or enriched foods like margarine.

Elevated blood low-density lipoprotein cholesterol (LDL-C) is a major risk factor for CVD, especially for coronary heart disease (CHD) resulting from atherosclerosis. We studied the dose-response relationship between dietary phytosterols and blood LDL-C in two meta-analyses (Chapters 2 and 3). A meta-analysis of 81 randomized controlled trials (Chapter 2) demonstrated a non-linear, continuous dose-response relationship for the LDL-C-lowering effect of phytosterols. Based on this dose-response curve, it may be predicted that phytosterols at a dose of 2 g/d lower LDL-C by 0.35 mmol/L or 9%. The dose-response curve reached a plateau at phytosterol doses of ~3 g/d, above which there is limited additional LDL-C-lowering effect. In another meta-analysis of 124 randomized controlled trials (Chapter 3), we showed that plant sterols and plant stanols up to ~3 g/d are equally effective in lowering LDL-C by a maximum of 12%. No conclusions could be drawn for phytosterol doses exceeding 4 g/d because of the limited number of studies.

Elevated blood triglycerides (TGs) may also be involved in the onset of CVD, although its role is less established than for LDL-C. The effect of plant sterols on blood TG concentrations was assessed in a meta-analysis of individual subject data from 12 randomized controlled trials (Chapter 4). We showed that plant sterols, at a dose of ~2 g/d, modestly reduce TG concentrations by on average 0.12 mmol/L or 6%. The TG-lowering effect of plant sterols was larger in subjects with higher initial TG concentrations. Our double-blind, placebo-controlled, randomized trial with 332 subjects (Chapter 5) showed more pronounced TG-lowering effects of 9-16% when plant sterols (2.5 g/d) were combined with low doses of omega-3 fish fatty acids (0.9 to 1.8 g/d).

Dietary phytosterols are, after initial absorption by intestinal cells, actively excreted back into the intestinal lumen. Nevertheless, small amounts reach the circulation. We assessed the effect of plant sterol intake on blood plant sterol concentrations in a meta-analysis of 41 randomized controlled trials (Chapter 6). The intake of plant sterols, at a dose of ~1.6 g/d, increased blood sitosterol concentrations by on average 2 μmol/L (31%) and campesterol concentrations by 5 μmol/L (37%). At the same time, total cholesterol and LDL-C concentrations were reduced by on average 0.36 mmol/L (6%) and 0.33 mmol/L (9%), respectively. After supplemental intake, plant sterol concentrations remained below 1% of total sterols circulating in the blood.

Whether phytosterols, due to their LDL-C-lowering properties, affect the risk of CVD events is at present unknown. The relation between phytosterol intake from natural sources (e.g. vegetables, cereals, nuts) and CVD risk in the population was examined in a large prospective cohort of 35,597 Dutch men and women with 12 years of follow-up (Chapter 7). The intake of phytosterols from natural sources (~300 mg/d) was not related to risk of CVD (total of 3,047 events) with a relative risk ranging from 0.90 to 0.99 across quintiles of phytosterol intake. Also, no association with incident CHD and myocardial infarction were found. In a cross-sectional analysis using baseline data of this cohort, phytosterol intake was associated with lower blood LDL-C in men (-0.18 mmol/L per 50 mg/d; 95% CI: -0.29; -0.08) but not in women (-0.03 mmol/L; 95% CI: -0.08; 0.03).

Most randomized trials with enriched foods have tested phytosterol doses between 1.5 and 2.4 g/d. In practice, however, users of such foods consume much lower amounts (~1 g/d), which is about 3 times higher than obtained from a regular Western diet. Individuals who consume diets with emphasis on plant-based foods (e.g. vegetarians) may reach phytosterol intakes between 0.5 and 1 g/d. Health authorities recommend various types of diets for CVD prevention, almost all rich in plant-based foods and, consequently, relatively rich in phytosterols.

In conclusion, a high intake of phytosterols with enriched foods was shown to lower LDL-C in a dose-dependent manner. Furthermore, a high intake of plant sterols with enriched foods modestly lowered TG concentrations and increased plasma plant sterol concentrations. A low intake of naturally occurring phytosterols in the general population did not show a clear association with CVD risk. Based on these findings, the intake of phytosterols may be considered in the management of hypercholesterolemia. Whether a high intake of phytosterols can play a role in CVD prevention in the population at large remains to be established.

Lifestyle factors and risk of cardiovascular diseases
Hoevenaar-Blom, M.P. - \ 2013
Wageningen University. Promotor(en): Daan Kromhout, co-promotor(en): W.M.M. Verschuren; A.M.W. Spijkerman. - S.l. : s.n. - ISBN 9789461735072 - 119
hart- en vaatziekten - levensstijl - risicofactoren - dieet - lichamelijke activiteit - slaap - cardiovascular diseases - lifestyle - risk factors - diet - physical activity - sleep

Background

Evidence is accumulating that lifestyle factors influence the incidence of fatal and non-fatal cardiovascular diseases (CVD). A healthy diet, being physically active, moderate alcohol consumption and not smoking are associated with a lower CVD risk. In addition to these lifestyle factors, recent research suggests that poor sleep may also be a risk factor of CVD. In this thesis, we focussed on a Mediterranean style diet, specific leisure time physical activities, and sleep duration and quality as risk factors for CVD.

Methods

Our analyses are based on the prospective Doetinchem Cohort Study (N ~ 3 400), the Monitoring Project on Risk Factors for Chronic Diseases (MORGEN) Study (N ~ 20 400) and the Dutch contribution to the European Prospective Investigation into Cancer and Nutrition (EPIC-NL) (N ~ 34 700). These studies included men and women aged 20-65 years when examined between 1993 and 1997. Diet was assessed with the validated EPIC food frequency questionnaire and operationalized with the Mediterranean Diet Score (MDS, range: 0-9). Physical activity was estimated with the validated EPIC physical activity questionnaire, with an emphasis on different leisure time activities. In addition, information was collected on duration and quality of sleep by two questions. Cardiovascular morbidity and mortality were ascertained through linkage with national registers. Multivariable Cox models were used to estimate the strength of the associations and 95% confidence intervals.

Results

During 12 years of follow-up, 206 CVD cases occurred in the Doetinchem Cohort Study, 1 486 cases in the MORGEN Study and 4 881 cases in the EPIC-NL Study. In the study on diet, a two unit increment in MDS was associated with a 22% lower risk of fatal CVD, and a 5% lower risk of total CVD. For specific CVDs, a 14% lower risk of myocardial infarction, a 12% lower risk of stroke, and a 26% lower risk of pulmonary embolism was observed. The MDS was not related to incident angina pectoris, transient ischemic attack and peripheral arterial disease. The use of multiple measurements of the MDS increased the strength of the associations with CVD and narrowed the confidence intervals. For leisure time physical activity, we showed that cycling was associated with an 18% lower risk of total CVD, sports with a 26% lower risk, and those who both cycled and performed sports had a 34% lower risk. Walking and gardening were not associated with CVD risk. Short sleep duration was associated with a 15% higher risk of total CVD, whereas long sleep duration and sleep quality separately were not associated. Short sleepers with a poor sleep quality had a 63% higher risk of total CVD compared to those with a normal sleep duration and good sleep quality. Finally, the combination of a healthy diet, sufficient physical activity, moderate alcohol consumption and non-smoking was associated with a 57% lower risk of composite CVD and a 67% lower risk of fatal CVD. The addition of sufficient sleep duration to these four traditional healthy lifestyle factors resulted in a 65% lower risk of composite CVD and an 83% lower risk of fatal CVD.

Conclusions

In this thesis, we showed that the strength of the association between dietary patterns and CVD incidence is likely underestimated because most studies used only the baseline measurement of diet. Furthermore, leisure time physical activities should be of at least moderate intensity to contribute to lower CVD risk. We also observed that sufficient sleep is a factor that should be taken into consideration in the prevention of CVD, in combination with a healthy diet, sufficient physical activity, moderate alcohol consumption and not smoking. Our results underscore the importance of a healthy lifestyle for CVD prevention.


Zout, bloeddruk en hart- en vaatziekten
Geleijnse, J.M. - \ 2011
In: Hart- en vaatziekten in Nederland 2011 / Vaartjes, I., van Dis, I., Visseren, F.L.J., Bots, M.L., Den Haag : Hartstichting - ISBN 9789075131703 - p. 73 - 90.
zout - reductie - hart- en vaatziekten - bloeddruk - hypertensie - natriumchloride - zoutgehalte - ziektepreventie - gezondheidsbevordering - salt - reduction - cardiovascular diseases - blood pressure - hypertension - sodium chloride - salinity - disease prevention - health promotion
Dit hoofdstuk richt zich op het belang van zoutreductie in de Nederlandse bevolking, waarbij achtereenvolgens het verband met bloeddruk en hart- en vaatziekten, de dagelijkse zoutinname en bronnen van zout, de potentiële gezondheidswinst door zoutreductie en lopende initiatieven op het gebied van zoutreductie in de bevolking besproken worden.
Cardiovascular risk prediction in the Netherlands
Dis, S.J. van - \ 2011
Wageningen University. Promotor(en): Daan Kromhout, co-promotor(en): W.M.M. Verschuren; Marianne Geleijnse. - [S.l.] : S.n. - ISBN 9789461730893
hart- en vaatziekten - risicoschatting - obesitas - afstamming - genetische effecten - nederland - cardiovascular diseases - risk assessment - obesity - parentage - genetic effects - netherlands

Background: In clinical practice, Systematic COronary Risk Evaluation (SCORE) risk prediction functions and charts are used to identify persons at high risk for cardiovascular diseases (CVD), who are considered eligible for drug treatment of elevated blood pressure and serum cholesterol. These functions use classical risk factors (age, gender, smoking, blood pressure and the ratio of total-to-HDL-cholesterol) to predict absolute 10-year risk of CVD mortality rather than total (fatal plus nonfatal) CVD. The aim of this thesis was to improve cardiovascular risk prediction in the Netherlands and to correctly classify high-risk persons.

Methods: We primarily used data from the Monitoring Project on Chronic Disease Risk Factors (MORGEN project) of the National Institute for Public Health and the Environment (RIVM). Risk factor data of more than 20,000 men and women aged 20-65 years were collected between 1993 and 1997. Ten-year follow up data on CVD mortality and morbidity were obtained from Statistics Netherlands and the National Hospital Discharge Register, respectively. Risk functions were developed using multivariable Cox proportional hazard models.

Results: The SCORE risk function for low-risk countries was the best predictor of CVD mortality in the Netherlands. Total CVD was approximately four times higher than CVD mortality. Obesity (BMI ≥30 kg/m2) and parental history of myocardial infarction before age 70 were independent predictors of total CVD. Risk functions predicting risk of CVD mortality and total CVD, and their ability to discriminate between future cases and non-cases, did not differ. Of the high-risk persons with a CVD mortality risk of at least 5%, approximately 20% developed a nonfatal or fatal CVD event during 10 years of follow-up. When a cut-off point of 2% CVD mortality was used, approximately 10% of the high-risk persons developed a CVD event. When obesity and parental history of MI were added to the classical risk factor function, correct risk classification improved by 5%. This improvement in risk prediction was mainly due to obesity.

Conclusions: Discrimination between future cases and non-cases did not improve by expanding the endpoint of risk prediction from fatal CVD to total CVD. Adding obesity and parental history to the classical risk factor functions slightly increased the number of correctly classified persons.

The intake of polyunsaturated fatty acids and cardiovascular diseases
Goede, J. de - \ 2011
Wageningen University. Promotor(en): Daan Kromhout, co-promotor(en): Marianne Geleijnse; W.M.M. Verschuren. - [s.l.] : S.n. - ISBN 9789461730480 - 160
meervoudig onverzadigde vetzuren - hart- en vaatziekten - voedselopname - visconsumptie - biomarkers - polyenoic fatty acids - cardiovascular diseases - food intake - fish consumption

Background

Despite a large amount of research in the past decades, the role of polyunsaturated fatty acids (PUFA) in the prevention of coronary heart disease (CHD) and stroke is still debated. Inconsistent findings in epidemiological studies may be due to methodological limitations of dietary assessment, which could be overcome by using PUFA levels in blood as a biomarker of intake. This thesis investigates dietary intake and plasma levels of various n-6 and n-3 PUFA in relation to CHD and stroke within a population-based sample in the Netherlands.

Methods

The associations of dietary intake of PUFA (assessed by food-frequency questionnaire) with incident CHD and stroke were examined in cohort studies. PUFA levels in plasma cholesteryl esters were measured in nested case-control studies. N-6 PUFA included linoleic acid and arachidonic acid and the n-3 PUFA included the marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the plant-derived alpha-linolenic acid (ALA). We used the “Monitoring Project on Cardiovascular Disease Risk Factors“ and the “Monitoring Project on Risk Factors for Chronic Diseases” (MORGEN study), two large similar population-based cohorts with baseline measurements in 1987-1997 and follow-up for CHD and stroke incidence. Additionally, we performed a meta-analysis of prospective epidemiological studies on PUFA in cholesteryl esters and CHD risk.

Results

A 4-5 en% difference in linoleic acid intake was not associated with incident CHD, whereas plasma linoleic acidwas inversely, but statistically non-significantly, associated with fatal CHD. In the meta-analysis, a 5% higher plasma linoleic acid level was related to a significant 9% lower CHD risk. Both ALA intake and status were not associated with CHD. The top quartiles of EPA-DHA (~250 mg/d) and fish intake (~1 fish meal/week) were related to a ~50% lower risk of fatal CHD compared to the bottom quartiles. However, this was not confirmed in plasma EPA-DHA. An ALA intake ≥1.1 g/d was associated with a 35-50% lower stroke incidence, compared with lower intakes. In women, but not in men, a significantly inverse relation was observed for EPA-DHA and fish intake with incident stroke, with a ~50% lower risk in the top quartile compared with the bottom quartile. Plasma PUFA levels were, however, not related to incident stroke.

Conclusion

The hypothesis of a beneficial effect of linoleic acid on CHD was confirmed in our biomarker study, but not in the study that used dietary intake data. For EPA-DHA, on the other hand, dietary intake was inversely related to fatal CHD and incident stroke, whereas cholesteryl ester EPA-DHA were not associated. The same applied to ALA intake in relation to incident stroke. Inconsistencies between PUFA intake and status with cardiovascular diseases could be attributed to the limited range of variation in PUFA intake in combination with measurement error.

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