A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown. Applying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis. In 40 studies including up to 133,449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9·45%, 95% CI 8·34-10·57) as well as reduced C-reactive protein (decrease per allele 8·35%, 95% CI 7·31-9·38) and fibrinogen concentrations (decrease per allele 0·85%, 95% CI 0·60-1·10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4-8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25,458 coronary heart disease cases and 100,740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0·95, 95% CI 0·93-0·97, p=1·53×10(-5)). On the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses. UK Medical Research Council; British Heart Foundation; Rosetrees Trust; US National Heart, Lung, and Blood Institute; Du Pont Pharma; Chest, Heart and Stroke Scotland; Wellcome Trust; Coronary Thrombosis Trust; Northwick Park Institute for Medical Research; UCLH/UCL Comprehensive Medical Research Centre; US National Institute on Aging; Academy of Finland; Netherlands Organisation for Health Research and Development; SANCO; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Agentschap NL; European Commission; Swedish Heart-Lung Foundation; Swedish Research Council; Strategic Cardiovascular Programme of the Karolinska Institutet; Stockholm County Council; US National Institute of Neurological Disorders and Stroke; MedStar Health Research Institute; GlaxoSmithKline; Dutch Kidney Foundation; US National Institutes of Health; Netherlands Interuniversity Cardiology Institute of the Netherlands; Diabetes UK; European Union Seventh Framework Programme; National Institute for Healthy Ageing; Cancer Research UK; MacArthur Foundation.

Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. The funding sources are cited at the end of the paper.

The aims of this study were to explore associations of the distance and use of urban green spaces with the prevalence of cardiovascular diseases (CVD) and its risk factors, and to evaluate the impact of the accessibility and use of green spaces on the incidence of CVD among the population of Kaunas city (Lithuania).

Body appreciation is one of the main facets of a positive body image. The present study aimed to examine the psychometric properties of the Lithuanian version of the Body Appreciation Scale-2 (BAS-2-LT) and test the associations between body appreciation and disordered eating in a large sample of adolescents of both genders. Method: The sample consisted of 1412 adolescents (40.2% were boys). The ages ranged from 15 to 18 years (92.4% were 17), with a mean age of 16.9 (SD = 0.5) for girls and 17.0 (SD = 0.4) for boys. Participants completed the BAS-2-LT alongside the measures of body dissatisfaction, disordered eating, body mass index, self-esteem, body functionality, and participation in sports. Linear regressions were used to test the associations between study variables and disordered eating. Results: BAS-2-LT replicated the original one-dimensional structure in girls and boys. Invariance across genders was established. The instrument showed good internal consistency and temporal stability. Body appreciation was negatively correlated with higher levels of body mass index, body dissatisfaction, and disordered eating. Positive associations were observed between body appreciation, self-esteem, body functionality, and sports participation. Higher levels of body appreciation decreased the risk of disordered eating behaviors in both genders. Conclusions: The results of the present study support the psychometric properties of BAS-2-LT. Body appreciation is associated with lower disordered eating in adolescent girls and boys. These findings present empirical support for the development of interventions programs that promote positive body images and aim to prevent disordered eating in adolescent boys and girls.

The present study aimed to explore the associations between body image concerns, body weight evaluation, disordered eating, nutrition habits, self-esteem, and physical activity (PA) in a mixed sample of adolescents of both genders. Methods. A total sample of 579 adolescents (299, 51.6% were girls) participated in this study. The participants ranged in age from 14–16 years old (M = 15.0, SD = 0.4). Respondents provided their answers filling in the questionnaires consisting of a battery of self-report questionnaires. An analysis of covariance was employed to test the hypothesis about the differences in body image concerns in the groups of BMI and body weight estimation controlling for gender. Results. Adolescents with a higher body mass index (BMI) and those overestimating body weight reported a higher body dissatisfaction (BD), a drive for thinness (DT), social physique anxiety (SPA), disordered eating, and lower self-esteem, but there were no differences in PA. Body weight overestimation was more prevalent in girls, yet body weight underestimation was more prevalent in boys. In girls, a higher BMI and body weight overestimation were associated with having less sweets, a lower frequency of having breakfast and for just a lower BMI alone—with consuming less fats, spreads, and oils. In boys, the BMI was associated with consuming less fruits and berries. The boys’ body weight overestimation was related to a lower reported number of meals, a lower frequency of breakfast, and a lower consumption of milk, cheese, yogurt, fats, spreads, and oils. Body dissatisfaction in boys and girls was negatively related to the number of meals, DT is related to a lower breakfast consumption (in girls), SPA was related to a lower nutrition score (in boys), the number of meals (boys and girls), and a lower use of meat and vegetables (boys). Conclusions. Adolescents with a higher BMI and body weight overestimation demonstrated higher body image concerns, lower self-esteem and a poorer eating-related behavioural profile. Body image concerns and body weight overestimation did not promote healthy behaviour in adolescents. It is critical to promote a positive body image, adequate body weight evaluation, self-esteem, and a healthy lifestyle in health promotion and health education programs for adolescents of both genders and different BMIs.