Smoking initiation, continuation and prevalence in deprived urban areas compared to non-deprived urban areas in The Netherlands

Previous studies have shown that smoking prevalence is higher in deprived areas than in affluent areas. We aimed to determine whether smoking initiation or continuation contributes most to inequalities in current smoking, and in which population subgroups these area differences were largest. Therefore, we assessed the relationship between area deprivation and current smoking, initiation and continuation in urban areas, in subgroups defined by gender, generation and educational level. Cross-sectional data of 20,603 Dutch adults (18 years and over) living in 963 urban areas in The Netherlands were obtained from the annual national health survey (2003-2009). Three interrelated smoking outcomes were used: current smoking (smokers/total population), initiation (ever-smokers/total population) and continuation (smokers/ever-smokers). Area deprivation was dichotomised; deprived urban areas (as defined by the Dutch government) and non-deprived urban areas (reference group) were distinguished. Multilevel logistic regression models controlled for individual characteristics (including education and income) and tested for interaction with gender, generation and education. After controlling for individual characteristics, odds for smoking were not significantly higher in deprived areas (current smoking: OR = 1.04 [0.92-1.18], initiation: OR = 1.05 [0.93-1.18], continuation: OR = 1.03 [0.88-1.19]). For smoking initiation, significant differences between deprived areas and other areas remained in younger generations (OR = 1.19 [1.02-1.38]) and higher educated (OR = 1.23 [1.04-1.45]) respondents. For continuation and current smoking, after controlling for individual characteristics, no associations were found in any subgroups. In conclusion, area deprivation appears to be independently related to smoking initiation in, respectively, higher educated and younger generations. These results suggest that initiatives to reduce area-level inequalities in smoking should focus on preventing smoking initiation in deprived area

Why residents of Dutch deprived neighbourhoods are less likely to be heavy drinkers: the role of individual and contextual characteristics

Earlier research has shown that residents of Dutch deprived neighbourhoods drink less alcohol than people in other areas. We aimed to assess the role of individual and neighbourhood characteristics in a cross-sectional, nationwide, multilevel study. Individual data of 30,117 Dutch adults, living in 1722 neighbourhoods across the Netherlands, were obtained from the 2004 to 2009 national health survey (POLS). Chronic heavy alcohol consumption was measured as ≥14 drinks/week for women and ≥21 for men, and episodic heavy drinking as ≥6 drinks/day at least once a week. Neighbourhood deprivation was dichotomous; deprived districts as selected by the Dutch government versus other areas. Multilevel logistic regression models of the association between deprivation and heavy drinking were corrected for age, gender, household composition, population density and potential predictors ethnicity, socioeconomic status (education, income), neighbourhood-level social cohesion and percentage Muslims. The prevalence of heavy drinking was lower in deprived neighbourhoods than in the rest of the Netherlands. This association was found for both chronic and episodic heavy drinking (OR=0.58 (0.47 to 0.72) and OR=0.57 (0.45 to 0.72), respectively). Adding ethnicity to the model reduced these associations by approximately one half. Socioeconomic composition did not contribute to the relationship. The proportion of Muslims explained a small part, while social cohesion explained even less of the association. Stronger associations were observed for women and older adults than for men and younger adults. The lower prevalence of heavy drinking occurring in deprived areas is largely explained by the ethnicity of neighbourhood resident

Transintestinal and Biliary Cholesterol Secretion Both Contribute to Macrophage Reverse Cholesterol Transport in RatsBrief Report

Objective-Reverse cholesterol transport comprises efflux of cholesterol from macrophages and its subsequent removal from the body with the feces and thereby protects against formation of atherosclerotic plaques. Because of lack of suitable animal models that allow for evaluation of the respective contributions of biliary cholesterol secretion and transintestinal cholesterol excretion (TICE) to macrophage reverse cholesterol transport under physiological conditions, the relative importance of both pathways in this process has remained controversial. Approach and Results-To separate cholesterol traffic via the biliary route from TICE, bile flow was mutually diverted between rats, continuously, for 3 days. Groups of 2 weight-matched rats were designated as a pair, and both rats were equipped with cannulas in the bile duct and duodenum. Bile from rat 1 was diverted to the duodenum of rat 2, whereas bile from rat 2 was rerouted to the duodenum of rat 1. Next, rat 1 was injected with [H-3] cholesterol-loaded macrophages. [H-3] Cholesterol secreted via the biliary route was consequently diverted to rat 2 and could thus be quantified from the feces of that rat. On the other hand, [H-3] cholesterol tracer in the feces of rat 1 reflected macrophage-derived cholesterol excreted via TICE. Using this setup, we found that 63% of the label secreted with the fecal neutral sterols had travelled via the biliary route, whereas 37% was excreted via TICE. Conclusions-TICE and biliary cholesterol secretion contribute to macrophage reverse cholesterol transport in rats. The majority of macrophage-derived cholesterol is however excreted via the hepatobiliary route. Visual Overview-An online visual overview is available for this article

Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

The role of the intestine in the maintenance of cholesterol homeostasis increasingly is recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) contribute. The mechanisms controlling the flux of cholesterol through the TICE pathway, however, are poorly understood. We aimed to identify mechanisms that regulate and stimulate TICE. We performed studies with C57Bl/6J mice, as well as with mice with intestine-specific knockout of the farnesoid X receptor (FXR), mice that express an FXR transgene specifically in the intestine, and ABCG8-knockout mice. Mice were fed a control diet or a diet supplemented with the FXR agonist PX20606, with or without the cholesterol absorption inhibitor ezetimibe. Some mice with intestine-specific knockout of FXR were given daily injections of fibroblast growth factor (FGF)19. To determine fractional cholesterol absorption, mice were given intravenous injections of cholesterol D5 and oral cholesterol D7. Mice were given (13)C-acetate in drinking water for measurement of cholesterol synthesis. Bile cannulations were performed and biliary cholesterol secretion rates were assessed. In a separate set of experiments, bile ducts of male Wistar rats were exteriorized, allowing replacement of endogenous bile by a model bile. In mice, we found TICE to be regulated by intestinal FXR via induction of its target gene Fgf15 (FGF19 in rats and human beings). Stimulation of this pathway caused mice to excrete up to 60% of their total cholesterol content each day. PX20606 and FGF19 each increased the ratio of muricholate:cholate in bile, inducing a more hydrophilic bile salt pool. The altered bile salt pool stimulated robust secretion of cholesterol into the intestinal lumen via the sterol-exporting heterodimer adenosine triphosphate binding cassette subfamily G member 5/8 (ABCG5/G8). Of note, the increase in TICE induced by PX20606 was independent of changes in cholesterol absorption. Hydrophilicity of the bile salt pool, controlled by FXR and FGF15/19, is an important determinant of cholesterol removal via TICE. Strategies that alter bile salt pool composition might be developed for the prevention of cardiovascular disease. Transcript profiling: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=irsrayeohfcntqx&acc=GSE7410

Tailored anticoagulant treatment after a first venous thromboembolism: protocol of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study - cohort-based randomised controlled trial

Introduction Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks.Methods and analysis The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients.Ethics and dissemination The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences.Trial registration number NCT06087952