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

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

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

Single-conformation spectroscopy of hydrogen bonding networks: Solvation, synthetic foldamers, and neurodegenerative diseases

The hydrogen bond is one of the most important interactions in natural processes ranging from protein folding to chemical reactions. Two complementary methodologies are applied to understanding this important interaction: top-down and bottom-up. Top-down methods use large molecules, such as proteins, revealing secondary structure information. Bottom-up experiments are performed on small molecules, utilizing high-resolution spectroscopy to reveal underlying quantum mechanical effects. The complexity gap is formed between these two experimental regimes; between large and small molecules; between bulk and individual solvent molecules; between classical mechanics calculations and quantum chemical calculations. This dissertation will focus on the application of gas phase, single-conformation ultraviolet (UV) and infrared (IR) spectroscopies to the study of molecules and clusters in the size and solvation complexity gap, with the goal of bridging the gulf between the two experimental approaches. Single-conformation spectroscopy is perfectly suited to study solvation. Solvent molecules, in many instances water, can be frozen onto the solute in a stepwise manner. Here, we solvate a prototypical flexible bichromophore—1,2-diphenoxyethane (DPOE)—by stepwise addition of water molecules. Single-conformation spectroscopy reveals both the structural perturbations associated with water molecule addition and their effect on DPOE’s pair of closely spaced excited electronic states. These experimental studies provide excellent insight into solvent effects on vibronic and excitonic coupling, and can be used to further develop the models used to describe such processes. Similarly, single-conformation spectroscopy can reveal the effects of conformational flexibility on the innate conformational preferences and hydrogen bonding motifs in peptides. Results obtained from a study of a cyclically constrained γ peptide, γACHC, reveal that increased conformational flexibility can be controlled by synthetic chemists in order to direct folding into pre-programmed secondary structures and that these structures are stabilized with intramolecular rather than intermolecular hydrogen bonds. This theme of conformational flexibility is continued in studies of glutamine containing peptides. Glutamine—with its flexible, hydrogen bond forming sidechain—is intimately involved with neurodegenerative diseases such as Huntington’s disease. Single-conformation studies help reveal the delicate interplay between three different types of hydrogen bonds within the molecule: backbone-backbone, sidechain-backbone, and sidechain-sidechain hydrogen bonds. The importance of these competing hydrogen bonds on the conformational preferences will be discussed both locally and within the larger context of disease pathogenesis

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

Associations between the urban exposome and type 2 diabetes: Results from penalised regression by least absolute shrinkage and selection operator and random forest models

BACKGROUND: Type 2 diabetes (T2D) is thought to be influenced by environmental stressors such as air pollution and noise. Although environmental factors are interrelated, studies considering the exposome are lacking. We simultaneously assessed a variety of exposures in their association with prevalent T2D by applying penalised regression Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Artificial Neural Networks (ANN) approaches. We contrasted the findings with single-exposure models including consistently associated risk factors reported by previous studies. METHODS: Baseline data (n = 14,829) of the Occupational and Environmental Health Cohort study (AMIGO) were enriched with 85 exposome factors (air pollution, noise, built environment, neighbourhood socio-economic factors etc.) using the home addresses of participants. Questionnaires were used to identify participants with T2D (n = 676(4.6 %)). Models in all applied statistical approaches were adjusted for individual-level socio-demographic variables. RESULTS: Lower average home values, higher share of non-Western immigrants and higher surface temperatures were related to higher risk of T2D in the multivariable models (LASSO, RF). Selected variables differed between the two multi-variable approaches, especially for weaker predictors. Some established risk factors (air pollutants) appeared in univariate analysis but were not among the most important factors in multivariable analysis. Other established factors (green space) did not appear in univariate, but appeared in multivariable analysis (RF). Average estimates of the prediction error (logLoss) from nested cross-validation showed that the LASSO outperformed both RF and ANN approaches. CONCLUSIONS: Neighbourhood socio-economic and socio-demographic characteristics and surface temperature were consistently associated with the risk of T2D. For other physical-chemical factors associations differed per analytical approach

Multimorbidity in Heart Failure: Leveraging Cluster Analysis to Guide Tailored Treatment Strategies

Review Purpose: This review summarises key findings on treatment effects within phenotypical clusters of patients with heart failure (HF), making a distinction between patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Findings: Treatment response differed among clusters; ACE inhibitors were beneficial in all HFrEF phenotypes, while only some studies show similar beneficial prognostic effects in HFpEF patients. Beta-blockers had favourable effects in all HFrEF patients but not in HFpEF phenotypes and tended to worsen prognosis in older, cardiorenal patients. Mineralocorticoid receptor antagonists had more favourable prognostic effects in young, obese males and metabolic HFpEF patients. While a phenotype-guided approach is a promising solution for individualised treatment strategies, there are several aspects that still require improvements before such an approach could be implemented in clinical practice. Summary: Stronger evidence from clinical trials and real-world data may assist in establishing a phenotype-guided treatment approach for patient with HF in the future

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

Скульптура Азербайджана в трудах русских искусствоведов (в 60-80-х годах прошлого столетия)

CONTEXT: The Metabolic Syndrome (MetS) is a cluster of metabolic abnormalities and is associated with increased risk of diabetes and cardiovascular diseases. Phylloquinone, menaquinones, and vitamin K status are associated with several components of MetS, but the association with MetS has hardly been studied to date. OBJECTIVE: This study aimed to examine whether the intake and/or status of vitamin K is associated with MetS and its components. DESIGN: This study comprised two cohorts, one of 402 women and one of 400 men (age 40-80 y). At followup 625 participants were still alive and willing to participate. Data were analyzed both cross sectionally and longitudinally with Poisson and linear regression adjusted for multiple confounders. Baseline phylloquinone/menaquinone intakes were measured with a validated food frequency questionnaire and vitamin K status with serum desphospho-uncarborxylated matrix-Gla protein level. RESULTS: At baseline 270 (34.5%) participants had MetS and 171 (35.7%) at followup. Cross sectionally, high menaquinones intakes were associated (P(trend) = .08) with a lower prevalence of MetS with a prevalence ratio (PR) of 0.74 (95% confidence interval [CI], 0.54-1.03) for the highest vs the lowest tertile. At followup, the highest tertiles of menaquinones intake (PR = 0.62; 95% CI, 0.40-0.95) and vitamin K status (PR = 0.57; 95% CI, 0.38-0.87) were associated (P(trend) = .01) with a lower occurrence of MetS. These associations were mainly driven by relations with lower triacylglycerol concentrations for menaquinones and lower waist circumference for vitamin K status. Phylloquinone intake was not associated with MetS prevalence. CONCLUSIONS: This study shows that a high intake of menaquinones and high vitamin K status are associated with a lower occurrence of MetS

Vascular uptake on 18F-sodium fluoride positron emission tomography:precursor of vascular calcification?

Background: Microcalcifications cannot be identified with the present resolution of CT; however, 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) imaging has been proposed for non-invasive identification of microcalcification. The primary objective of this study was to assess whether 18F-NaF activity can assess the presence and predict the progression of CT detectable vascular calcification. Methods and Results: The data of two longitudinal studies in which patients received a 18F-NaF PET-CT at baseline and after 6 months or 1-year follow-up were used. The target to background ratio (TBR) was measured on PET at baseline and CT calcification was quantified in the femoral arteries at baseline and follow-up. 128 patients were included. A higher TBR at baseline was associated with higher calcification mass at baseline and calcification progression (β = 1.006 [1.005-1.007] and β = 1.002 [1.002-1.003] in the studies with 6 months and 1-year follow-up, respectively). In areas without calcification at baseline and where calcification developed at follow-up, the TBR was.11–.13 (P < .001) higher compared to areas where no calcification developed. Conclusion: The activity of 18F-NaF is related to the amount of calcification and calcification progression. In areas where calcification formation occurred, the TBR was slightly but significantly higher