Profile of patients with inflammatory bowel disease in conjunction with unmet needs and decision-making for choosing a new biologic therapy: a baseline analysis of the VEDOIBD-Study.

PURPOSE: We characterized the profile of Crohn's disease (CD) or ulcerative colitis (UC) biologic-naïve patients (starting a new therapy with vedolizumab or TNFα-antagonists), their baseline disease activity predictors, and their perception of the quality of life (HRQoL). METHODS: The VEDOIBD-Study is a real-world study on the effectiveness of vedolizumab vs other biologics as induction and maintenance therapy for CD and UC. A total of 627 CD and 546 UC patients were enrolled from IBD-experienced centers across Germany. In both biologic-naïve vedolizumab (n=397) and anti-TNF (n=359) patients, CD and UC disease severity and HRQoL predictors were analyzed with logistic regression. The results were reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: When compared to biologic-naïve anti-TNF patients, a first biological therapy with vedolizumab was considered for older CD patients, with a less complicated though longer disease course, and with a history of comorbidities. No differences in (unmet) needs were observed among patients with UC. The presence of extra-intestinal manifestations in biologic-naïve anti-TNF patients with CD (OR (95% CI): 3.83 (1.69-8.68)) and, in both biologic-naïve groups of patients with UC, stool frequency (2.00 (1.25-3.19); 1.82 (1.10-3.02), respectively) and rectal bleeding (2.24 (1.20-4.18); 1.92 (1.19-3.11), respectively) emerged as the most important predictors of disease severity, which in turn were also significantly associated with a worse HRQoL. CONCLUSION: This study highlights the existence of unmet medical needs of patients with CD or UC, for whom a new biological therapy is planned as part of the VEDOIBD-Study, which considerably impacts their HRQoL.

Association of Circulating Vitamin E (α- and γ-Tocopherol) Levels with Gallstone Disease.

In addition to well-established risk factors like older age, female gender, and adiposity, oxidative stress may play a role in the pathophysiology of gallstone disease. Since vitamin E exerts important anti-oxidative functions, we hypothesized that circulating vitamin E levels might be inversely associated with prevalence of gallstone disease. In a cross-sectional study, we measured plasma levels of α- and γ-tocopherol using high performance liquid chromatography in a community-based sample (582 individuals; median age 62 years; 38.5% women). Gallstone disease status was assessed by ultrasound. Multivariable-adjusted logistic regression models were used to estimate the association of circulating α- and γ-tocopherol/cholesterol ratio levels with prevalent gallstone disease. Lower probabilities of having gallstone disease were observed in the top (compared to the bottom) tertile of the plasma α-tocopherol/cholesterol ratio in multivariable-adjusted models (OR (Odds Ratio): 0.31; 95% CI (Confidence Interval): 0.13-0.76). A lower probability of having gallstone disease was also observed for the γ-tocopherol/cholesterol ratio, though the association did not reach statistical significance (OR: 0.77; 95% CI: 0.35-1.69 for 3rd vs 1st tertile). In conclusion, our observations are consistent with the concept that higher vitamin E levels might protect from gallstone disease, a premise that needs to be further addressed in longitudinal studies.

Vitamin E (α- and γ-Tocopherol) Levels in the Community: Distribution, Clinical and Biochemical Correlates, and Association with Dietary Patterns.

Little is known about the distribution and determinants of circulating vitamin E levels in a German population. In this cross-sectional study we assessed the distribution of both α- and γ-tocopherol levels, identified their clinical and biochemical correlates, and assessed their relationships with a priori and a posteriori derived dietary patterns. Plasma α- and γ-tocopherol concentrations were measured using high performance liquid chromatography (HPLC) with fluorescence detection in 641 individuals (mean-age: 61 years; 40.6% women). Correlates of both markers were determined using linear regression with backward selection. Using a validated food-frequency questionnaire (FFQ), an a priori defined vitamin E-rich dietary pattern was constructed, and three a posteriori derived dietary patterns were identified by principal component analysis. Each pattern was related to α- and γ-tocopherol levels using linear regression. Median concentrations of α- and γ-tocopherol were 31.54 µmol/L and 1.35 µmol/L, respectively. 57.6% of participants had α-tocopherol levels >30 µmol/L. Triglycerides, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, and vitamin E supplementation were identified as correlates of vitamin E levels. After excluding supplement users, a dietary pattern rich in meat, bread, fats, potatoes, and sugar/confectionery was inversely related to α-tocopherol levels (ß, -0.032, SE = 0.016; p = 0.047). Prospective studies are warranted to evaluate the actual impact of the reported findings in terms of nutrition and health outcomes.

Potential Predictors of Plasma Fibroblast Growth Factor 23 Concentrations: Cross-Sectional Analysis in the EPIC-Germany Study.

BACKGROUND: Increased fibroblast growth factor 23 (FGF23), a bone-derived hormone involved in the regulation of phosphate and vitamin D metabolism, has been related to the development of cardiovascular disease (CVD) in chronic kidney disease patients and in the general population. However, what determines higher FGF23 levels is still unclear. Also, little is known about the influence of diet on FGF23. The aim of this study was therefore to identify demographic, clinical and dietary correlates of high FGF23 concentrations in the general population. METHODS: We performed a cross-sectional analysis within a randomly selected subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany comprising 2134 middle-aged men and women. The Human FGF23 (C-Terminal) ELISA kit was used to measure FGF23 in citrate plasma. Dietary data were obtained at baseline via validated food frequency questionnaires including up to 148 food items. RESULTS: Multivariable adjusted logistic regression showed that men had a 66% lower and smokers a 64% higher probability of having higher FGF23 (≥ 90 RU/mL) levels compared, respectively, with women and nonsmokers. Each doubling in parathyroid hormone, creatinine, and C-reactive protein was related to higher FGF23. Among the dietary factors, each doubling in calcium and total energy intake was related, respectively, to a 1.75 and to a 4.41 fold increased probability of having higher FGF23. Finally, each doubling in the intake of iron was related to an 82% lower probability of having higher FGF23 levels. Results did not substantially change after exclusion of participants with lower kidney function. CONCLUSIONS: In middle-aged men and women traditional and non-traditional CVD risk factors were related to higher FGF23 concentrations. These findings may contribute to the understanding of the potential mechanisms linking increased FGF23 to increased CVD risk.

Consumption of cocoa, tea and coffee and risk of cardiovascular disease.

Daily intake of an anti-thrombotic diet may offer a suitable and effective way of coronary artery disease (CAD) prevention. A diet rich in fruit, vegetables, complex carbohydrates, monounsaturated fat and fish, moderate alcohol consumption but poor in salt, saturated fat and simple sugars, plays an important role in protect against CAD. Chocolate, coffee and tea, unfairly not included in "traditional healthy food basket", have received much attention over the past few years, if for no other reason than they are consumed worldwide and are important dietary sources of polyphenols (flavonols and cathechins). Several in vitro and in vivo studies have tried to elucidate the role of these foods and a large amount of experimental studies clearly indicated a beneficial effect of polyphenols in influencing CAD. However, data from epidemiological studies are not conclusive. The blood pressure lowering effects and the anti-inflammatory activity of dark chocolate suggests its use as potential prophylactic and therapeutic agent, in particular considering that epidemiological studies suggest that dark chocolate is inversely associated with CAD. Although regular consumption of moderate quantities of coffee and (green) tea seems to be associated with a small protection against CAD, results from randomized clinical trials about their beneficial effects are less evident. As for other diffuse consumption habits, such as that of alcohol, moderation is the key word. In fact, both for coffee and chocolate, the optimal healthy effects on CAD have been observed to be associated with a moderate intake, while healthy outcomes vanish at heavy consumption.

Alcohol consumption and cardiovascular risk: mechanisms of action and epidemiologic perspectives.

An inverse association between moderate alcohol intake and cardiovascular risk, in particular coronary disease and ischemic stroke, has been demonstrated in many epidemiologic studies. In addition, several not primarily vascular diseases are also known to occur less frequently in moderate drinkers than in nondrinkers, whereas excess drinking is unquestionably harmful. As a consequence, strong concern exists on the possibility that at any dosage the benefit of alcohol could overcome its harmful effects. Alcohol affects several biochemical factors that have potential cardioprotective benefits, including lipids, platelet aggregation, fibrinogen, tissue-plasminogen activator, plasminogen-activator inhibitor and omega-3 fatty acids. Wine possibly acts through mechanisms that might provide additional cardiovascular benefits. Mechanisms supporting the protective effect of moderate alcohol intake against cardiovascular disease, and epidemiologic evidence concerning the relationship between alcohol dosing and vascular and all-cause mortality are discussed in this review.