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13 december 2022, Item does not contain fulltext

Contains fulltext : 282324.pdf (Publisher’s version ) (Open Access), BACKGROUND: Vitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients. OBJECTIVES: We aimed to assess the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD. METHODS: We performed a multicenter, double-blind, randomized controlled trial. COPD patients with ≥1 exacerbations in the preceding year and a vitamin D deficiency (15-50 nmol/L) were randomly allocated in a 1:1 ratio to receive either 16,800 International Units (IU) vitamin D3 or placebo once a week during 1 y. Primary outcome of the study was exacerbation rate. Secondary outcomes included time to first and second exacerbations, time to first and second hospitalizations, use of antibiotics and corticosteroids, pulmonary function, maximal respiratory mouth pressure, physical performance, skeletal muscle strength, systemic inflammatory markers, nasal microbiota composition, and quality of life. RESULTS: The intention-to-treat population consisted of 155 participants. Mean ± SD serum 25-hydroxyvitamin D [25(OH)D] concentration after 1 y was 112 ± 34 nmol/L in the vitamin D group, compared with 42 ± 17 nmol/L in the placebo group. Vitamin D supplementation did not affect exacerbation rate [incidence rate ratio (IRR): 0.90; 95% CI: 0.67, 1.21]. In a prespecified subgroup analysis in participants with 25(OH)D concentrations of 15-25 nmol/L (n = 31), no effect of vitamin D supplementation was found (IRR: 0.91; 95% CI: 0.43, 1.93). No relevant differences were found between the intervention and placebo groups in terms of secondary outcomes. CONCLUSIONS: Vitamin D supplementation did not reduce exacerbation rate in COPD patients with a vitamin D deficiency.This trial was registered at clinicaltrials.gov as NCT02122627.

13 december 2022, Item does not contain fulltext

Contains fulltext : 282324.pdf (Publisher’s version ) (Open Access), BACKGROUND: Vitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients. OBJECTIVES: We aimed to assess the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD. METHODS: We performed a multicenter, double-blind, randomized controlled trial. COPD patients with ≥1 exacerbations in the preceding year and a vitamin D deficiency (15-50 nmol/L) were randomly allocated in a 1:1 ratio to receive either 16,800 International Units (IU) vitamin D3 or placebo once a week during 1 y. Primary outcome of the study was exacerbation rate. Secondary outcomes included time to first and second exacerbations, time to first and second hospitalizations, use of antibiotics and corticosteroids, pulmonary function, maximal respiratory mouth pressure, physical performance, skeletal muscle strength, systemic inflammatory markers, nasal microbiota composition, and quality of life. RESULTS: The intention-to-treat population consisted of 155 participants. Mean ± SD serum 25-hydroxyvitamin D [25(OH)D] concentration after 1 y was 112 ± 34 nmol/L in the vitamin D group, compared with 42 ± 17 nmol/L in the placebo group. Vitamin D supplementation did not affect exacerbation rate [incidence rate ratio (IRR): 0.90; 95% CI: 0.67, 1.21]. In a prespecified subgroup analysis in participants with 25(OH)D concentrations of 15-25 nmol/L (n = 31), no effect of vitamin D supplementation was found (IRR: 0.91; 95% CI: 0.43, 1.93). No relevant differences were found between the intervention and placebo groups in terms of secondary outcomes. CONCLUSIONS: Vitamin D supplementation did not reduce exacerbation rate in COPD patients with a vitamin D deficiency.This trial was registered at clinicaltrials.gov as NCT02122627.

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Contains fulltext : 247486.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 237637.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 247486.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 247486.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 193359.pdf (publisher's version ) (Open Access), BACKGROUND: Alcohol and tobacco use are heritable phenotypes. However, only a small number of common genetic variants have been identified, and common variants account for a modest proportion of the heritability. Therefore, this study aims to investigate the role of low-frequency and rare variants in alcohol and tobacco use. METHODS: We meta-analyzed ExomeChip association results from eight discovery cohorts and included 12,466 subjects and 7432 smokers in the analysis of alcohol consumption and tobacco use, respectively. The ExomeChip interrogates low-frequency and rare exonic variants, and in addition a small pool of common variants. We investigated top variants in an independent sample in which ICD-9 diagnoses of "alcoholism" (N=25,508) and "tobacco use disorder" (N=27,068) had been assessed. In addition to the single variant analysis, we performed gene-based, polygenic risk score (PRS), and pathway analyses. RESULTS: The meta-analysis did not yield exome-wide significant results. When we jointly analyzed our top results with the independent sample, no low-frequency or rare variants reached significance for alcohol consumption or tobacco use. However, two common variants that were present on the ExomeChip, rs16969968 (p=2.39x10(-7)) and rs8034191 (p=6.31x10(-7)) located in CHRNA5 and AGPHD1 at 15q25.1, showed evidence for association with tobacco use. DISCUSSION: Low-frequency and rare exonic variants with large effects do not play a major role in alcohol and tobacco use, nor does the aggregate effect of ExomeChip variants. However, our results confirmed the role of the CHRNA5-CHRNA3-CHRNB4 cluster of nicotinic acetylcholine receptor subunit genes in tobacco use.

Contains fulltext : 193359.pdf (publisher's version ) (Open Access), BACKGROUND: Alcohol and tobacco use are heritable phenotypes. However, only a small number of common genetic variants have been identified, and common variants account for a modest proportion of the heritability. Therefore, this study aims to investigate the role of low-frequency and rare variants in alcohol and tobacco use. METHODS: We meta-analyzed ExomeChip association results from eight discovery cohorts and included 12,466 subjects and 7432 smokers in the analysis of alcohol consumption and tobacco use, respectively. The ExomeChip interrogates low-frequency and rare exonic variants, and in addition a small pool of common variants. We investigated top variants in an independent sample in which ICD-9 diagnoses of "alcoholism" (N=25,508) and "tobacco use disorder" (N=27,068) had been assessed. In addition to the single variant analysis, we performed gene-based, polygenic risk score (PRS), and pathway analyses. RESULTS: The meta-analysis did not yield exome-wide significant results. When we jointly analyzed our top results with the independent sample, no low-frequency or rare variants reached significance for alcohol consumption or tobacco use. However, two common variants that were present on the ExomeChip, rs16969968 (p=2.39x10(-7)) and rs8034191 (p=6.31x10(-7)) located in CHRNA5 and AGPHD1 at 15q25.1, showed evidence for association with tobacco use. DISCUSSION: Low-frequency and rare exonic variants with large effects do not play a major role in alcohol and tobacco use, nor does the aggregate effect of ExomeChip variants. However, our results confirmed the role of the CHRNA5-CHRNA3-CHRNB4 cluster of nicotinic acetylcholine receptor subunit genes in tobacco use.

Contains fulltext : 177320.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, Purpose To test the hypothesis that hepatic triglyceride content is associated with subclinical vascular impairment and is not confounded by various cardiometabolic risk factors. Materials and Methods This study was approved by the institutional review board, and all participants gave written informed consent. In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, a population-based cohort study, 1899 participants (52% men; mean age, 55 years +/- 6 [standard deviation]) underwent magnetic resonance (MR) spectroscopy and MR imaging to assess hepatic triglyceride content, aortic pulse wave velocity (PWV), and visceral fat. Carotid intima-media thickness (IMT) was acquired and measured by trained research nurses according to standard procedures. Multivariate regression analyses were used to study associations of hepatic triglyceride content with total and regional aortic PWV and carotid IMT while adjusting for several possible confounding factors, including the metabolic syndrome. Results Total aortic PWV (mean difference, 0.5 m/sec; 95% confidence interval [CI]: 0.3, 0.7) and carotid IMT (mean difference, 37 mum; 95% CI: 25, 49) were higher in participants with hepatic steatosis. After adjusting for various covariates, a 10-fold increase in hepatic triglyceride content was associated with an increased mean aortic PWV of 0.19 m/sec (95% CI: 0.03, 0.36) in total and an increased mean aortic PWV of 0.42 m/sec (95% CI: 0.03, 0.81) in the abdominal segment. A 10-fold increase in hepatic triglyceride content was also associated with an increased mean carotid IMT of 15 mum (95% CI: 0, 29) but not after additional adjustments for visceral and total body fat. Conclusion In this relatively large population-based cohort study, hepatic triglyceride content was associated with aortic pulse wave velocity and carotid IMT. These associations were only partly explained by the metabolic syndrome and visceral adiposity, suggesting a p

Contains fulltext : 177320.pdf (publisher's version ) (Open Access)

14 september 2017, Item does not contain fulltext

Contains fulltext : 177320.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, Purpose To test the hypothesis that hepatic triglyceride content is associated with subclinical vascular impairment and is not confounded by various cardiometabolic risk factors. Materials and Methods This study was approved by the institutional review board, and all participants gave written informed consent. In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, a population-based cohort study, 1899 participants (52% men; mean age, 55 years +/- 6 [standard deviation]) underwent magnetic resonance (MR) spectroscopy and MR imaging to assess hepatic triglyceride content, aortic pulse wave velocity (PWV), and visceral fat. Carotid intima-media thickness (IMT) was acquired and measured by trained research nurses according to standard procedures. Multivariate regression analyses were used to study associations of hepatic triglyceride content with total and regional aortic PWV and carotid IMT while adjusting for several possible confounding factors, including the metabolic syndrome. Results Total aortic PWV (mean difference, 0.5 m/sec; 95% confidence interval [CI]: 0.3, 0.7) and carotid IMT (mean difference, 37 mum; 95% CI: 25, 49) were higher in participants with hepatic steatosis. After adjusting for various covariates, a 10-fold increase in hepatic triglyceride content was associated with an increased mean aortic PWV of 0.19 m/sec (95% CI: 0.03, 0.36) in total and an increased mean aortic PWV of 0.42 m/sec (95% CI: 0.03, 0.81) in the abdominal segment. A 10-fold increase in hepatic triglyceride content was also associated with an increased mean carotid IMT of 15 mum (95% CI: 0, 29) but not after additional adjustments for visceral and total body fat. Conclusion In this relatively large population-based cohort study, hepatic triglyceride content was associated with aortic pulse wave velocity and carotid IMT. These associations were only partly explained by the metabolic syndrome and visceral adiposity, suggesting a p

14 september 2017, Item does not contain fulltext

14 september 2017, Item does not contain fulltext

Item does not contain fulltext, Purpose To test the hypothesis that hepatic triglyceride content is associated with subclinical vascular impairment and is not confounded by various cardiometabolic risk factors. Materials and Methods This study was approved by the institutional review board, and all participants gave written informed consent. In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, a population-based cohort study, 1899 participants (52% men; mean age, 55 years +/- 6 [standard deviation]) underwent magnetic resonance (MR) spectroscopy and MR imaging to assess hepatic triglyceride content, aortic pulse wave velocity (PWV), and visceral fat. Carotid intima-media thickness (IMT) was acquired and measured by trained research nurses according to standard procedures. Multivariate regression analyses were used to study associations of hepatic triglyceride content with total and regional aortic PWV and carotid IMT while adjusting for several possible confounding factors, including the metabolic syndrome. Results Total aortic PWV (mean difference, 0.5 m/sec; 95% confidence interval [CI]: 0.3, 0.7) and carotid IMT (mean difference, 37 mum; 95% CI: 25, 49) were higher in participants with hepatic steatosis. After adjusting for various covariates, a 10-fold increase in hepatic triglyceride content was associated with an increased mean aortic PWV of 0.19 m/sec (95% CI: 0.03, 0.36) in total and an increased mean aortic PWV of 0.42 m/sec (95% CI: 0.03, 0.81) in the abdominal segment. A 10-fold increase in hepatic triglyceride content was also associated with an increased mean carotid IMT of 15 mum (95% CI: 0, 29) but not after additional adjustments for visceral and total body fat. Conclusion In this relatively large population-based cohort study, hepatic triglyceride content was associated with aortic pulse wave velocity and carotid IMT. These associations were only partly explained by the metabolic syndrome and visceral adiposity, suggesting a p

Contains fulltext : 177320.pdf (publisher's version ) (Open Access)

15 februari 2016, Item does not contain fulltext

Radboud Universiteit Nijmegen, 27 januari 2016, Promotores : Heijer, M. den, Hermus, A.R.M.M. Co-promotor : Netea-Maier, R.T., Contains fulltext : 150187.pdf (publisher's version ) (Open Access)

15 februari 2016, Item does not contain fulltext

Radboud Universiteit Nijmegen, 27 januari 2016, Promotores : Heijer, M. den, Hermus, A.R.M.M. Co-promotor : Netea-Maier, R.T., Contains fulltext : 150187.pdf (publisher's version ) (Open Access)

Radboud Universiteit Nijmegen, 27 januari 2016, Promotores : Heijer, M. den, Hermus, A.R.M.M. Co-promotor : Netea-Maier, R.T., Contains fulltext : 150187.pdf (publisher's version ) (Open Access)

Item does not contain fulltext, BACKGROUND AND OBJECTIVES: Increased iron and metabolic syndrome (MetS) go hand in hand. Frequent blood donation depletes iron stores. This study investigates whether high-intensity blood donation is associated with lower MetS prevalence compared with low-intensity blood donation, and whether iron acts as an intermediary factor. MATERIALS AND METHODS: A random sample of 422 male and 211 female active whole-blood donors >/=45 years of age was included in a cross-sectional study. Lipids, glucose and iron parameters were measured after overnight fasting. MetS was defined according to the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Three groups of donation intensity were created by sex-specific tertiles of donation frequency per year and duration of donor career. RESULTS: MetS was present in 22.9% of donors. Prevalence of MetS was 1.46 (95% confidence interval [CI]: 0.93-2.30) times higher in men with high donation intensity, whereas in women MetS prevalence was 2.14 (95% CI: 0.94-4.86) times higher in donors with high donation intensity compared with those with low donation intensity. In men, increased prevalence of MetS was mainly associated with higher ferritin, whereas high hepcidin predominantly affected MetS prevalence in women. CONCLUSION: High-intensity blood donation is not associated with a decreased prevalence of MetS. In men and women, different iron parameters are associated with MetS prevalence. The temporal relationship between blood donation, iron and MetS, and gender differences herein need to be explored in future research.

Contains fulltext : 154296.pdf (publisher's version ) (Closed access), BACKGROUND: In populations with mild iodine deficiency, the serum level of thyrotropin (TSH) is negatively and the serum free thyroxine (FT4) is positively associated with age. An ongoing decrease of TSH and increase of FT4 can be found after iodine supplementation. The aim of this study was to investigate whether there are current differences in the relation between thyroid function and age in relation to differences in iodine intake in the past. METHODS: Eight medical laboratories in several regions of The Netherlands, which are all iodine sufficient at present but with a difference in iodine status in the past, provided the results of all TSH and FT4 measurements performed from 2006 until 2011, resulting in 330,802 TSH and 103,940 FT4 measurements. RESULTS: The negative association between TSH and age in the elderly is only present in areas with a historical iodine deficiency (regression coefficients [RC] -0.008, 95% confidence interval [CI] -0.009; -0.007). In the historically iodine-sufficient population, TSH shows no obvious increase or decrease with age. In both the historically iodine-sufficient and iodine-deficient populations, FT4 levels were positively associated with age in the elderly (RC 0.009, 95% CI 0.008; 0.010 and RC 0.008, 95% CI 0.007; 0.010, respectively). CONCLUSIONS: There are differences in relation between thyroid function and age between populations with differences in iodine intake in the past, despite an adequate iodine status at present. This raises the question whether the present but also historical iodine status of a population should be taken into account when establishing the reference limits of TSH and FT4.

Contains fulltext : 153230.pdf (publisher's version ) (Open Access), BACKGROUND: Previous reports suggested a role for iron and hepcidin in atherosclerosis. Here, we evaluated the causality of these associations from a genetic perspective via (i) a Mendelian randomization (MR) approach, (ii) study of association of atherosclerosis-related single nucleotide polymorphisms (SNPs) with iron and hepcidin, and (iii) estimation of genomic correlations between hepcidin, iron and atherosclerosis. RESULTS: Analyses were performed in a general population sample. Iron parameters (serum iron, serum ferritin, total iron-binding capacity and transferrin saturation), serum hepcidin and genome-wide SNP data were available for N = 1,819; non-invasive measurements of atherosclerosis (NIMA), i.e., presence of plaque, intima media thickness and ankle-brachial index (ABI), for N = 549. For the MR, we used 12 iron-related SNPs that were previously identified in a genome-wide association meta-analysis on iron status, and assessed associations of individual SNPs and quartiles of a multi-SNP score with NIMA. Quartile 4 versus quartile 1 of the multi-SNP score showed directionally consistent associations with the hypothesized direction of effect for all NIMA in women, indicating that increased body iron status is a risk factor for atherosclerosis in women. We observed no single SNP associations that fit the hypothesized directions of effect between iron and NIMA, except for rs651007, associated with decreased ferritin concentration and decreased atherosclerosis risk. Two of six NIMA-related SNPs showed association with the ratio hepcidin/ferritin, suggesting that an increased hepcidin/ferritin ratio increases atherosclerosis risk. Genomic correlations were close to zero, except for hepcidin and ferritin with ABI at rest [-0.27 (SE 0.34) and -0.22 (SE 0.35), respectively] and ABI after exercise [-0.29 (SE 0.34) and -0.30 (0.35), respectively]. The negative sign indicates an increased atherosclerosis risk with increased hepcidin and ferritin concentrations. CONC

Radboud Universiteit Nijmegen, 1 december 2015, Promotores : Verbeek, A.L.M., Heijer, M. den Co-promotor : Atsma, F., Contains fulltext : 149279.pdf (publisher's version ) (Open Access), In this thesis, the possible protective effect of frequent blood donation on cardiovascular disease was studied. Previous research has shown that high iron stores could have damaging effects on developing cardiovascular disease, and that blood donation lowers iron stores. Lowering iron stores through blood donation could therefore reduce cardiovascular disease risk. Apart from the effects on insulin resistance, metabolic syndrome, and subclinical atherosclerosis, the effects on cardiovascular morbidity and –mortality were also studied. For this purpose, data of Dutch blood donors were linked to hospital discharges and death certificates as registered at Statistics Netherlands (CBS). Within the group of people that have remained an active donor for at least 10 years, high-frequency donors (> 20 donations in men, >15 donations in women) have a significantly lower cardiovascular risk than low-frequency donors (<15 donations in men, <12 donations in women). Women appeared to have a 10% lower risk on cardiovascular disease incidence, and even 17% on cardiovascular death. Frequent blood donors are relatively healthy compared to the general population, and high-frequency donors could already have been healthier than low-frequency donors. This Healthy Donor Effect could have influenced the results. Therefore, further research on the protective effect of blood donation on cardiovascular disease is needed. Future research focussed on replicating these results, as well as the underlying causal mechanism, should take differences between men and women into account.

Item does not contain fulltext, BACKGROUND: In general practice, it is too time-consuming to invite all patients for cardiovascular risk assessment. OBJECTIVE: To examine how many patients with an indication for treatment with cardiovascular medication can be identified by ad hoc case-finding when all patients with overweight/obesity are invited for risk assessment. METHODS: A cross-sectional analysis of the baseline measurements of the Netherlands Epidemiology of Obesity study, a population-based prospective cohort study in 6673 persons aged 45-65 years. We calculated the proportion of participants with a treatment indication using the risk prediction Systematic COronary Risk Evaluation (SCORE-NL 2011), for lean, overweight and obese participants. Participants with a history of cardiovascular disease, diabetes mellitus or rheumatoid arthritis or using cardiovascular medication were not eligible for ad hoc case-finding because they were already identified as being at risk and/or had been treated. Results : Of the study population, 30% had already been identified and/or treated with cardiovascular medication and were therefore not eligible for ad hoc case-finding. Of the eligible participants, 47% were lean, 41% overweight and 12% obese. Of the participants with overweight, 12% had a treatment indication and of the participants with obesity, 19% had a treatment indication. Of all participants with a treatment indication 24% were not yet treated. Of all participants with a new treatment indication, 70% had overweight or obesity. CONCLUSIONS: Of the participants with a treatment indication, 24% were not yet treated. Inviting patients with overweight/obesity for cardiovascular risk assessment may help to detect 70% of these residual patients with a treatment indication.

Item does not contain fulltext, OBJECTIVE: To study the relative contribution of surrogates for mechanical stress and systemic processes with osteoarthritis (OA) in weight-bearing and non-weight-bearing joints. METHODS: The Netherlands Epidemiology of Obesity study is a population-based cohort including 6673 participants (range 45-65 years, 56% women, median body mass index 26 kg/m(2)). Weight (kg) and fat mass (kg) were measured, fat-free mass (kg) was calculated. The metabolic syndrome was defined following the Adult Treatment Panel III criteria. Knee and hand OA were defined according to the American College of Rheumatology clinical criteria.Logistic regression analyses were performed to associate surrogates for mechanical stress (such as weight, fat-free mass) and systemic processes (such as metabolic syndrome) with OA in knees alone, knees and hands or hands alone, adjusted for age, sex, height, smoking, education and ethnicity, and when appropriate for metabolic factors and weight. RESULTS: Knee, knee and hand, and hand OA were present in 10%, 4% and 8% of the participants, respectively. Knee OA was associated with weight and fat-free mass, adjusted for metabolic factors (OR 1.49 (95% CI 1.32 to 1.68) and 2.05 (1.60 to 2.62), respectively). Similar results were found for OA in knees and hands (OR 1.51 (95% CI 1.29 to 1.78) and 2.17 (95% CI 1.52 to 3.10) respectively). Hand OA was associated with the metabolic syndrome, adjusted for weight (OR 1.46 (95% CI 1.06 to 2.02)). CONCLUSIONS: In knee OA, whether or not in co-occurrence with hand OA, surrogates for mechanical stress are suggested to be the most important risk factors, whereas in hand OA alone, surrogates for systemic processes are the most important risk factors.

Contains fulltext : 153724.pdf (publisher's version ) (Open Access), BACKGROUND: Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients. METHODS/DESIGN: We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate. DISCUSSION: This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitam

Item does not contain fulltext, BACKGROUND: Both overall and abdominal adiposity are established risk factors for cardiovascular disease. Visceral adipose tissue (VAT) and total body fat (TBF) are strongly correlated and previous studies did not make this distinction. OBJECTIVE: We aimed to distinguish individual contributions of TBF, VAT, and the ratio of VAT to abdominal subcutaneous adipose tissue (VAT/SAT) to subclinical atherosclerosis in men and women. METHODS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity (NEO) study, we assessed VAT and SAT with magnetic resonance imaging, TBF with bio-electrical impendence analysis, and carotid Intima-Media Thickness (cIMT) with ultrasound. We performed linear regression analyses of standardized values of TBF, VAT, VAT/SAT with cIMT. We adjusted the models for confounding factors (age, sex, ethnicity, education, smoking, alcohol, physical activity), and either for VAT or TBF. RESULTS: This analysis included 2451 participants, 53% men with mean (SD) cIMT of 615 (91)mum. After adjustment for confounding factors, the difference in cIMT (95% CI) per SD in VAT was 14 (8,21)mum in men and 18 (13,24)mum in women. After adjustment for TBF, this attenuated to 5 (-3,13)mum in men and 13 (5,20)mum in women. In the full model, differences in cIMT (95% CI) per SD of TBF were 14 (6,22)mum in men and 8 (0,16)mum in women, and per SD of VAT/SAT were 7 (-1,15)mum and 9 (3,16)mum respectively. CONCLUSIONS: In this population-based study, VAT contributed beyond overall adiposity to subclinical atherosclerosis, particularly in women. This implies a specific role of VAT in the early development of atherosclerosis.

Item does not contain fulltext, BACKGROUND AND OBJECTIVES: Increased iron and metabolic syndrome (MetS) go hand in hand. Frequent blood donation depletes iron stores. This study investigates whether high-intensity blood donation is associated with lower MetS prevalence compared with low-intensity blood donation, and whether iron acts as an intermediary factor. MATERIALS AND METHODS: A random sample of 422 male and 211 female active whole-blood donors >/=45 years of age was included in a cross-sectional study. Lipids, glucose and iron parameters were measured after overnight fasting. MetS was defined according to the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Three groups of donation intensity were created by sex-specific tertiles of donation frequency per year and duration of donor career. RESULTS: MetS was present in 22.9% of donors. Prevalence of MetS was 1.46 (95% confidence interval [CI]: 0.93-2.30) times higher in men with high donation intensity, whereas in women MetS prevalence was 2.14 (95% CI: 0.94-4.86) times higher in donors with high donation intensity compared with those with low donation intensity. In men, increased prevalence of MetS was mainly associated with higher ferritin, whereas high hepcidin predominantly affected MetS prevalence in women. CONCLUSION: High-intensity blood donation is not associated with a decreased prevalence of MetS. In men and women, different iron parameters are associated with MetS prevalence. The temporal relationship between blood donation, iron and MetS, and gender differences herein need to be explored in future research.

Item does not contain fulltext, BACKGROUND: Both overall and abdominal adiposity are established risk factors for cardiovascular disease. Visceral adipose tissue (VAT) and total body fat (TBF) are strongly correlated and previous studies did not make this distinction. OBJECTIVE: We aimed to distinguish individual contributions of TBF, VAT, and the ratio of VAT to abdominal subcutaneous adipose tissue (VAT/SAT) to subclinical atherosclerosis in men and women. METHODS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity (NEO) study, we assessed VAT and SAT with magnetic resonance imaging, TBF with bio-electrical impendence analysis, and carotid Intima-Media Thickness (cIMT) with ultrasound. We performed linear regression analyses of standardized values of TBF, VAT, VAT/SAT with cIMT. We adjusted the models for confounding factors (age, sex, ethnicity, education, smoking, alcohol, physical activity), and either for VAT or TBF. RESULTS: This analysis included 2451 participants, 53% men with mean (SD) cIMT of 615 (91)mum. After adjustment for confounding factors, the difference in cIMT (95% CI) per SD in VAT was 14 (8,21)mum in men and 18 (13,24)mum in women. After adjustment for TBF, this attenuated to 5 (-3,13)mum in men and 13 (5,20)mum in women. In the full model, differences in cIMT (95% CI) per SD of TBF were 14 (6,22)mum in men and 8 (0,16)mum in women, and per SD of VAT/SAT were 7 (-1,15)mum and 9 (3,16)mum respectively. CONCLUSIONS: In this population-based study, VAT contributed beyond overall adiposity to subclinical atherosclerosis, particularly in women. This implies a specific role of VAT in the early development of atherosclerosis.

Contains fulltext : 154296.pdf (publisher's version ) (Closed access), BACKGROUND: In populations with mild iodine deficiency, the serum level of thyrotropin (TSH) is negatively and the serum free thyroxine (FT4) is positively associated with age. An ongoing decrease of TSH and increase of FT4 can be found after iodine supplementation. The aim of this study was to investigate whether there are current differences in the relation between thyroid function and age in relation to differences in iodine intake in the past. METHODS: Eight medical laboratories in several regions of The Netherlands, which are all iodine sufficient at present but with a difference in iodine status in the past, provided the results of all TSH and FT4 measurements performed from 2006 until 2011, resulting in 330,802 TSH and 103,940 FT4 measurements. RESULTS: The negative association between TSH and age in the elderly is only present in areas with a historical iodine deficiency (regression coefficients [RC] -0.008, 95% confidence interval [CI] -0.009; -0.007). In the historically iodine-sufficient population, TSH shows no obvious increase or decrease with age. In both the historically iodine-sufficient and iodine-deficient populations, FT4 levels were positively associated with age in the elderly (RC 0.009, 95% CI 0.008; 0.010 and RC 0.008, 95% CI 0.007; 0.010, respectively). CONCLUSIONS: There are differences in relation between thyroid function and age between populations with differences in iodine intake in the past, despite an adequate iodine status at present. This raises the question whether the present but also historical iodine status of a population should be taken into account when establishing the reference limits of TSH and FT4.

Contains fulltext : 153230.pdf (publisher's version ) (Open Access), BACKGROUND: Previous reports suggested a role for iron and hepcidin in atherosclerosis. Here, we evaluated the causality of these associations from a genetic perspective via (i) a Mendelian randomization (MR) approach, (ii) study of association of atherosclerosis-related single nucleotide polymorphisms (SNPs) with iron and hepcidin, and (iii) estimation of genomic correlations between hepcidin, iron and atherosclerosis. RESULTS: Analyses were performed in a general population sample. Iron parameters (serum iron, serum ferritin, total iron-binding capacity and transferrin saturation), serum hepcidin and genome-wide SNP data were available for N = 1,819; non-invasive measurements of atherosclerosis (NIMA), i.e., presence of plaque, intima media thickness and ankle-brachial index (ABI), for N = 549. For the MR, we used 12 iron-related SNPs that were previously identified in a genome-wide association meta-analysis on iron status, and assessed associations of individual SNPs and quartiles of a multi-SNP score with NIMA. Quartile 4 versus quartile 1 of the multi-SNP score showed directionally consistent associations with the hypothesized direction of effect for all NIMA in women, indicating that increased body iron status is a risk factor for atherosclerosis in women. We observed no single SNP associations that fit the hypothesized directions of effect between iron and NIMA, except for rs651007, associated with decreased ferritin concentration and decreased atherosclerosis risk. Two of six NIMA-related SNPs showed association with the ratio hepcidin/ferritin, suggesting that an increased hepcidin/ferritin ratio increases atherosclerosis risk. Genomic correlations were close to zero, except for hepcidin and ferritin with ABI at rest [-0.27 (SE 0.34) and -0.22 (SE 0.35), respectively] and ABI after exercise [-0.29 (SE 0.34) and -0.30 (0.35), respectively]. The negative sign indicates an increased atherosclerosis risk with increased hepcidin and ferritin concentrations. CONC

Radboud Universiteit Nijmegen, 01 december 2015, Promotores : Verbeek, A.L.M., Heijer, M. den Co-promotor : Atsma, F., Contains fulltext : 149279.pdf (publisher's version ) (Open Access), In this thesis, the possible protective effect of frequent blood donation on cardiovascular disease was studied. Previous research has shown that high iron stores could have damaging effects on developing cardiovascular disease, and that blood donation lowers iron stores. Lowering iron stores through blood donation could therefore reduce cardiovascular disease risk. Apart from the effects on insulin resistance, metabolic syndrome, and subclinical atherosclerosis, the effects on cardiovascular morbidity and –mortality were also studied. For this purpose, data of Dutch blood donors were linked to hospital discharges and death certificates as registered at Statistics Netherlands (CBS). Within the group of people that have remained an active donor for at least 10 years, high-frequency donors (> 20 donations in men, >15 donations in women) have a significantly lower cardiovascular risk than low-frequency donors (<15 donations in men, <12 donations in women). Women appeared to have a 10% lower risk on cardiovascular disease incidence, and even 17% on cardiovascular death. Frequent blood donors are relatively healthy compared to the general population, and high-frequency donors could already have been healthier than low-frequency donors. This Healthy Donor Effect could have influenced the results. Therefore, further research on the protective effect of blood donation on cardiovascular disease is needed. Future research focussed on replicating these results, as well as the underlying causal mechanism, should take differences between men and women into account.

Item does not contain fulltext, BACKGROUND: In general practice, it is too time-consuming to invite all patients for cardiovascular risk assessment. OBJECTIVE: To examine how many patients with an indication for treatment with cardiovascular medication can be identified by ad hoc case-finding when all patients with overweight/obesity are invited for risk assessment. METHODS: A cross-sectional analysis of the baseline measurements of the Netherlands Epidemiology of Obesity study, a population-based prospective cohort study in 6673 persons aged 45-65 years. We calculated the proportion of participants with a treatment indication using the risk prediction Systematic COronary Risk Evaluation (SCORE-NL 2011), for lean, overweight and obese participants. Participants with a history of cardiovascular disease, diabetes mellitus or rheumatoid arthritis or using cardiovascular medication were not eligible for ad hoc case-finding because they were already identified as being at risk and/or had been treated. RESULTS: Of the study population, 30% had already been identified and/or treated with cardiovascular medication and were therefore not eligible for ad hoc case-finding. Of the eligible participants, 47% were lean, 41% overweight and 12% obese. Of the participants with overweight, 12% had a treatment indication and of the participants with obesity, 19% had a treatment indication. Of all participants with a treatment indication 24% were not yet treated. Of all participants with a new treatment indication, 70% had overweight or obesity. CONCLUSIONS: Of the participants with a treatment indication, 24% were not yet treated. Inviting patients with overweight/obesity for cardiovascular risk assessment may help to detect 70% of these residual patients with a treatment indication.

Item does not contain fulltext, OBJECTIVE: To study the relative contribution of surrogates for mechanical stress and systemic processes with osteoarthritis (OA) in weight-bearing and non-weight-bearing joints. METHODS: The Netherlands Epidemiology of Obesity study is a population-based cohort including 6673 participants (range 45-65 years, 56% women, median body mass index 26 kg/m(2)). Weight (kg) and fat mass (kg) were measured, fat-free mass (kg) was calculated. The metabolic syndrome was defined following the Adult Treatment Panel III criteria. Knee and hand OA were defined according to the American College of Rheumatology clinical criteria.Logistic regression analyses were performed to associate surrogates for mechanical stress (such as weight, fat-free mass) and systemic processes (such as metabolic syndrome) with OA in knees alone, knees and hands or hands alone, adjusted for age, sex, height, smoking, education and ethnicity, and when appropriate for metabolic factors and weight. RESULTS: Knee, knee and hand, and hand OA were present in 10%, 4% and 8% of the participants, respectively. Knee OA was associated with weight and fat-free mass, adjusted for metabolic factors (OR 1.49 (95% CI 1.32 to 1.68) and 2.05 (1.60 to 2.62), respectively). Similar results were found for OA in knees and hands (OR 1.51 (95% CI 1.29 to 1.78) and 2.17 (95% CI 1.52 to 3.10) respectively). Hand OA was associated with the metabolic syndrome, adjusted for weight (OR 1.46 (95% CI 1.06 to 2.02)). CONCLUSIONS: In knee OA, whether or not in co-occurrence with hand OA, surrogates for mechanical stress are suggested to be the most important risk factors, whereas in hand OA alone, surrogates for systemic processes are the most important risk factors.

Contains fulltext : 153724.pdf (publisher's version ) (Open Access), BACKGROUND: Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients. METHODS/DESIGN: We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate. DISCUSSION: This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitam

Radboud Universiteit Nijmegen, 01 december 2015, Promotores : Verbeek, A.L.M., Heijer, M. den Co-promotor : Atsma, F., Contains fulltext : 149279.pdf (publisher's version ) (Open Access), In this thesis, the possible protective effect of frequent blood donation on cardiovascular disease was studied. Previous research has shown that high iron stores could have damaging effects on developing cardiovascular disease, and that blood donation lowers iron stores. Lowering iron stores through blood donation could therefore reduce cardiovascular disease risk. Apart from the effects on insulin resistance, metabolic syndrome, and subclinical atherosclerosis, the effects on cardiovascular morbidity and –mortality were also studied. For this purpose, data of Dutch blood donors were linked to hospital discharges and death certificates as registered at Statistics Netherlands (CBS). Within the group of people that have remained an active donor for at least 10 years, high-frequency donors (> 20 donations in men, >15 donations in women) have a significantly lower cardiovascular risk than low-frequency donors (<15 donations in men, <12 donations in women). Women appeared to have a 10% lower risk on cardiovascular disease incidence, and even 17% on cardiovascular death. Frequent blood donors are relatively healthy compared to the general population, and high-frequency donors could already have been healthier than low-frequency donors. This Healthy Donor Effect could have influenced the results. Therefore, further research on the protective effect of blood donation on cardiovascular disease is needed. Future research focussed on replicating these results, as well as the underlying causal mechanism, should take differences between men and women into account.

Item does not contain fulltext, OBJECTIVE: To study the relative contribution of surrogates for mechanical stress and systemic processes with osteoarthritis (OA) in weight-bearing and non-weight-bearing joints. METHODS: The Netherlands Epidemiology of Obesity study is a population-based cohort including 6673 participants (range 45-65 years, 56% women, median body mass index 26 kg/m(2)). Weight (kg) and fat mass (kg) were measured, fat-free mass (kg) was calculated. The metabolic syndrome was defined following the Adult Treatment Panel III criteria. Knee and hand OA were defined according to the American College of Rheumatology clinical criteria.Logistic regression analyses were performed to associate surrogates for mechanical stress (such as weight, fat-free mass) and systemic processes (such as metabolic syndrome) with OA in knees alone, knees and hands or hands alone, adjusted for age, sex, height, smoking, education and ethnicity, and when appropriate for metabolic factors and weight. RESULTS: Knee, knee and hand, and hand OA were present in 10%, 4% and 8% of the participants, respectively. Knee OA was associated with weight and fat-free mass, adjusted for metabolic factors (OR 1.49 (95% CI 1.32 to 1.68) and 2.05 (1.60 to 2.62), respectively). Similar results were found for OA in knees and hands (OR 1.51 (95% CI 1.29 to 1.78) and 2.17 (95% CI 1.52 to 3.10) respectively). Hand OA was associated with the metabolic syndrome, adjusted for weight (OR 1.46 (95% CI 1.06 to 2.02)). CONCLUSIONS: In knee OA, whether or not in co-occurrence with hand OA, surrogates for mechanical stress are suggested to be the most important risk factors, whereas in hand OA alone, surrogates for systemic processes are the most important risk factors.