Dietary Glycemic Load and Glycemic Index and Risk of Coronary Heart Disease and Stroke in Dutch Men and Women: The EPIC-MORGEN Study

BACKGROUND: The associations of glycemic load (GL) and glycemic index (GI) with the risk of cardiovascular diseases (CVD) are not well-established, particularly in men, and may be modified by gender. OBJECTIVE: To assess whether high dietary GL and GI increase the risk of CVD in men and women. METHODS: A large prospective cohort study (EPIC-MORGEN) was conducted within the general Dutch population among 8,855 men and 10,753 women, aged 21-64 years at baseline (1993-1997) and free of diabetes and CVD. Dietary intake was assessed with a validated food-frequency questionnaire and GI and GL were calculated using Foster-Powell's international table of GI. Information on morbidity and mortality was obtained through linkage with national registries. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for incident coronary heart disease (CHD) and stroke, while adjusting for age, CVD risk factors, and dietary factors. RESULTS: During a mean follow-up of 11.9 years, 581 CHD cases and 120 stroke cases occurred among men, and 300 CHD cases and 109 stroke cases occurred among women. In men, GL was associated with an increased CHD risk (adjusted HR per SD increase, 1.17 [95% CI, 1.02-1.35]), while no significant association was found in women (1.09 [0.89-1.33]). GI was not associated with CHD risk in both genders, while it was associated with increased stroke risk in men (1.27 [1.02-1.58]) but not in women (0.96 [0.75-1.22]). Similarly, total carbohydrate intake and starch intake were associated with a higher CHD risk in men (1.23 [1.04-1.46]; and 1.24 [1.07-1.45]), but not in women. CONCLUSION: Among men, high GL and GI, and high carbohydrate and starch intake, were associated with increased risk of CVD

Vitamin K status and physical decline in older adults—The Longitudinal Aging Study Amsterdam

Objective: We examined the association between vitamin K status and physical functioning over 13 years in the Longitudinal Aging Study Amsterdam. Study design: Longitudinal cohort study of 633 community-dwelling adults from the Longitudinal Aging Study Amsterdam (LASA) aged 55–65 years (54% women). Main outcome measures: At baseline (2002–2003), plasma desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) was measured with a sandwich ELISA as a marker of vitamin K status. The outcome measures handgrip strength, calf circumference, self-reported functional limitations and functional performance were obtained at baseline and four follow-up examinations. We used generalized estimating equations to determine the relationship between dp-ucMGP tertiles and the various outcome measurements after adjusting for potential confounders. The lowest dp-ucMGP tertile reflects a high vitamin K status and was the reference. Results: Mean dp-ucMGP was 376 ± 233 pmol/L and mean follow-up was 11.1 years. Participants showed a decline in the outcome measures over time. Compared with the lowest tertile, the highest dp-ucMGP tertile had: lower handgrip strength, 1.1 kg (95% confidence interval (−2.1, −0.1; P-trend <0.001); smaller calf circumference, −0.5 cm (−0.9 −0.1; P-trend = 0.018); and, only among women, a 0.7-point poorer functional performance score (−1.1, −0.3; P-interaction = 0.002). Dp-ucMGP was not related to self-reported functional limitations. No interaction effects between time and dp-ucMGP were observed. Conclusions: Low vitamin K status was associated with lower handgrip strength, smaller calf circumference, and, in women only, with poorer functional performance score. A low vitamin K status was however not related to the 13-year decline in these measures

A personalised screening strategy for diabetic retinopathy:a cost-effectiveness perspective

Aims/hypothesis: In this study we examined the cost-effectiveness of three different screening strategies for diabetic retinopathy: using a personalised adaptive model, annual screening (fixed intervals), and the current Dutch guideline (stratified based on previous retinopathy grade). Methods: For each individual, optimal diabetic retinopathy screening intervals were determined, using a validated risk prediction model. Observational data (1998–2017) from the Hoorn Diabetes Care System cohort of people with type 2 diabetes were used (n = 5514). The missing values of retinopathy grades were imputed using two scenarios of slow and fast sight-threatening retinopathy (STR) progression. By comparing the model-based screening intervals to observed time to develop STR, the number of delayed STR diagnoses was determined. Costs were calculated using the healthcare perspective and the societal perspective. Finally, outcomes and costs were compared for the different screening strategies. Results: For the fast STR progression scenario, personalised screening resulted in 11.6% more delayed STR diagnoses and €11.4 less costs per patient compared to annual screening from a healthcare perspective. The personalised screening model performed better in terms of timely diagnosis of STR (8.8% less delayed STR diagnosis) but it was slightly more expensive (€1.8 per patient from a healthcare perspective) than the Dutch guideline strategy. Conclusions/interpretation: The personalised diabetic retinopathy screening model is more cost-effective than the Dutch guideline screening strategy. Although the personalised screening strategy was less effective, in terms of timely diagnosis of STR patients, than annual screening, the number of delayed STR diagnoses is low and the cost saving is considerable. With around one million people with type 2 diabetes in the Netherlands, implementing this personalised model could save €11.4 million per year compared with annual screening, at the cost of 658 delayed STR diagnoses with a maximum delayed time to diagnosis of 48 months. Graphical abstract: [Figure not available: see fulltext.]

The role of menaquinones (vitamin K2) in human health

Recent reports have attributed the potential health benefits of vitamin K beyond its function to activate hepatic coagulation factors. Moreover, several studies have suggested that menaquinones, also known as vitamin K2, may be more effective in activating extra-hepatic vitamin K-dependent proteins than phylloquinone, also known as vitamin K1. Nevertheless, present dietary reference values (DRV) for vitamin K are exclusively based on phylloquinone, and its function in coagulation. The present review describes the current knowledge on menaquinones based on the following criteria for setting DRV: optimal dietary intake; nutrient amount required to prevent deficiency, maintain optimal body stores and/or prevent chronic disease; factors influencing requirements such as absorption, metabolism, age and sex. Dietary intake of menaquinones accounts for up to 25% of total vitamin K intake and contributes to the biological functions of vitamin K. However, menaquinones are different from phylloquinone with respect to their chemical structure and pharmacokinetics, which affects bioavailability, metabolism and perhaps impact on health outcomes. There are significant gaps in the current knowledge on menaquinones based on the criteria for setting DRV. Therefore, we conclude that further investigations are needed to establish how differences among the vitamin K forms may influence tissue specificities and their role in human health. However, there is merit for considering both menaquinones and phylloquinone when developing future recommendations for vitamin K intak

Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population:the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Background. Fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone that increases early in the course of chronic kidney disease (CKD), is associated with disease progression in patients with established CKD. Here we aimed to investigate the association between plasma FGF23 and new-onset CKD in the general population.Methods. We included 5253 individuals without CKD who participated in the Prevention of Renal and Vascular Endstage Disease study, a prospective, population-based cohort. Multi-variable Cox regression was used to study the association of plasma C-terminal FGF23 with new-onset CKD, defined as a combined endpoint of estimated glomerular filtration rate (eGFR) 30 mg/24 h or both, or with all-cause mortality.Results. The median baseline FGF23 was 68 [interquartile range (IQR) 56-85]RU/mL, eGFR was 9513mL/min/1.73m(2) and UAE was 7.8 (IQR 5.8-11.5) mg/24h. After follow-up of 7.5 (IQR 7.2-8.0) years, 586 participants developed CKD and 214 participants died. A higher FGF23 level was associated with new-onset CKD, independent of risk factors for kidney disease and parameters of bone and mineral homoeostasis {fully adjusted hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.10-1.44] per doubling of FGF23; P=0.001}. In secondary analyses, FGF23 was independently associated with new-onset eGFR 30mg/24h [adjusted HR 1.24 (95% CI 1.06-1.45); P=0.01] individually. A higher FGF23 level was also associated with an increased risk of all-cause mortality [fully adjusted HR 1.30 (95% CI 1.03-1.63); P=0.03].Conclusions. High FGF23 levels are associated with an increased risk of new-onset CKD and all-cause mortality in this prospective population-based cohort, independent of established CKD risk factors.</p

Reversal Of Arterial Disease by modulating Magnesium and Phosphate (ROADMAP-study):rationale and design of a randomized controlled trial assessing the effects of magnesium citrate supplementation and phosphate-binding therapy on arterial stiffness in moderate chronic kidney disease

Background: Arterial stiffness and calcification propensity are associated with high cardiovascular risk and increased mortality in chronic kidney disease (CKD). Both magnesium and phosphate are recognized as modulators of vascular calcification and chronic inflammation, both features of CKD that contribute to arterial stiffness. In this paper, we outline the rationale and design of a randomized controlled trial (RCT) investigating whether 24 weeks of oral magnesium supplementation with or without additional phosphate-binding therapy can improve arterial stiffness and calcification propensity in patients with stage 3-4 CKD. Methods: In this multi-center, placebo-controlled RCT, a total of 180 participants with an estimated glomerular filtration rate of 15 to 50 ml/min/1.73 m(2) without phosphate binder therapy will be recruited. During the 24 weeks intervention, participants will be randomized to one of four intervention groups to receive either magnesium citrate (350 mg elemental magnesium/day) or placebo, with or without the addition of the phosphate binder sucroferric oxyhydroxide (1000 mg/day). Primary outcome of the study is the change of arterial stiffness measured by the carotid-femoral pulse wave velocity over 24 weeks. Secondary outcomes include markers of calcification and inflammation, among others calcification propensity (T-50) and high-sensitivity C-reactive protein. As explorative endpoints, repeated F-18-FDG and F-18-NaF PET-scans will be performed in a subset of participants (n = 40). Measurements of primary and secondary endpoints are performed at baseline, 12 and 24 weeks. Discussion: The combined intervention of magnesium citrate supplementation and phosphate-lowering therapy with sucroferric oxyhydroxide, in stage 3-4 CKD patients without overt hyperphosphatemia, aims to modulate the complex and deregulated mineral metabolism leading to vascular calcification and arterial stiffness and to establish to what extent this is mediated by T(50 )changes. The results of this combined intervention may contribute to future early interventions for CKD patients to reduce the risk of CVD and mortality

Ставлення істориків українських земель другої половини XIX — початку XX ст. до релігії та церкви

У статті показані головні підходи істориків того періоду до важливих суспільних явищ, підкреслені відмінності підходи позитивістів та прихильників інших наукових парадигм.The article shows the main approaches of historians of that period to these important social phenomena, stresses the differences between the approaches of the positivists and supporters of other scientific paradigms

Neighbourhood drivability: environmental and individual characteristics associated with car use across Europe

Background: Car driving is a form of passive transportation associated with higher sedentary behaviour, which is associated with morbidity. The decision to drive a car is likely to be influenced by the ‘drivability’ of the built environment, but there is lack of scientific evidence regarding the relative contribution of environmental characteristics of car driving in Europe, compared to individual characteristics. This study aimed to determine which neighbourhood- and individual-level characteristics were associated with car driving in adults of five urban areas across Europe. Second, the study aimed to determine the percentage of variance in car driving explained by individual- and neighbourhood-level characteristics. Methods: Neighbourhood environment characteristics potentially related to car use were identified from the literature. These characteristics were subsequently assessed using a Google Street View audit and available GIS databases, in 59 administrative residential neighbourhoods in five European urban areas. Car driving (min/week) and individual level characteristics were self-reported by study participants (analytic sample n = 4258). We used linear multilevel regression analyses to assess cross-sectional associations of individual and neighbourhood-level characteristics with weekly minutes of car driving, and assessed explained variance at each level and for the total model. Results: Higher residential density (β:-2.61, 95%CI: − 4.99; -0.22) and higher land-use mix (β:-3.73, 95%CI: − 5.61; -1.86) were significantly associated with fewer weekly minutes of car driving. At the individual level, higher age (β: 1.47, 95%CI: 0.60; 2.33), male sex (β: 43.2, 95%CI:24.7; 61.7), being employed (β:80.1, 95%CI: 53.6; 106.5) and ≥ 3 person household composition (β: 47.4, 95%CI: 20.6; 74.2) were associated with higher weekly minutes of car driving. Individual and neighbourhood characteristics contributed about equally to explained variance in minutes of weekly car driving, with 2 and 3% respectively, but total explained variance remained low. Conclusions: Residential density and land-use mix were neighbourhood characteristics consistently associated with minutes of weekly car driving, besides age, sex, employment and household composition. Although total explained variance was low, both individual- and neighbourhood-level characteristics were similarly important in their associations with car use in five European urban areas. This study suggests that more, higher quality, and longitudinal data are needed to increase our understanding of car use and its effects on determinants of health

Urinary Ethyl Glucuronide as Measure of Alcohol Consumption and Risk of Cardiovascular Disease:A Population-Based Cohort Study

Background Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality compared with heavy drinkers and abstainers. To date, studies have relied on self-reported consumption, which may be prone to misclassification. Urinary ethyl glucuronide (EtG) is an alcohol metabolite and validated biomarker for recent alcohol consumption. We aimed to examine and compare the associations of self-reported alcohol consumption and EtG with CVD and all-cause mortality. Methods and Results In 5676 participants of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study cohort, EtG was measured in 24-hour urine samples and alcohol consumption questionnaires were administered. Participants were followed up for occurrence of first CVD and all-cause mortality. Cox proportional hazards regression models, adjusted for age, sex, and CVD risk factors, were fitted for self-reported consumption, divided into 5 categories: abstention, 1 to 4 units/month (reference), 2 to 7 units/week, 1 to 3 units/day, and ≥4 units/day. Similar models were fitted for EtG, analyzed as both continuous and categorical variables. Follow-up times differed for CVD (8 years; 385 CVD events) and all-cause mortality (14 years; 724 deaths). For both self-reported alcohol consumption and EtG, nonsignificant trends were found toward J-shaped associations between alcohol consumption and CVD, with higher risk in the lowest (hazard ratio for abstention versus 1-4 units/month, 1.42; 95% CI, 1.02-1.98) and highest drinking categories (hazard ratio for ≥4 units/day versus 1-4 units/month, 1.11; 95% CI, 0.68-1.84). Neither self-report nor EtG was associated with all-cause mortality. Conclusions Comparable associations with CVD events and all-cause mortality were found for self-report and EtG. This argues for the validity of self-reported alcohol consumption in epidemiologic research