SummaryBackgroundStatins 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.MethodsWe 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.FindingsData 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).InterpretationThe increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.FundingThe funding sources are cited at the end of the paper.

SummaryBackgroundA 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.MethodsApplying 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.FindingsIn 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).InterpretationOn 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.FundingUK 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; Nationa...

BackgroundThe 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).MethodsWe present the results from a Kaunas cohort study on the access to and use of green spaces, the association with cardiovascular risk factors and other health-related variables, and the risk of cardiovascular mortality and morbidity. A random sample of 5,112 individuals aged 45-72 years was screened in 2006-2008. During the mean 4.41 years follow-up, there were 83 deaths from CVD and 364 non-fatal cases of CVD among persons free from CHD and stroke at the baseline survey. Multivariate Cox proportional hazards regression models were used for data analysis.ResultsWe found that the distance from people’s residence to green spaces was not related to the prevalence of health-related variables. However, the prevalence of cardiovascular risk factors and the prevalence of diabetes mellitus were significantly lower among park users than among non-users. During the follow up, an increased risk of non-fatal and fatal CVD combined was observed for those who lived ≥629.61 m from green spaces (3rd tertile of distance to green space) (hazard ratio (HR) = 1.36), and the risk for non-fatal CVD–for those who lived ≥347.81 m (2nd and 3rd tertile) and were not park users (HR = 1.66) as compared to men and women who lived 347.8 m or less (1st tertile) from green space. Men living further away from parks (3rd tertile) had a higher risk of non-fatal and fatal CVD combined, compared to those living nearby (1st tertile) (HR = 1.51). Compared to park users living nearby (1st tertile), a statistically significantly increased risk of non-fatal CVD was observed for women who were not park users and living farther away from parks (2nd and 3rd tertile) (HR = 2.78).ConclusionOur analysis suggests public health policies aimed at promoting healthy lifestyles in urban settings could produce cardiovascular benefits.

The results of our study confirmed an association between use of the green space, residential proximity, and depressive symptoms and poor and very poor perceived general health among women only.

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.

The general aim of the present study was to examine how physical activity, participation in sports, and beliefs about personal physical activity and physical fitness are associated with adolescents’ psychosomatic health complaints (PHC) in relation to their lifestyles. Methods A total of 3284 11–19-year-old adolescents (average age 14.9 ± 2.0; 48.6% male) participated in the population-based cross-sectional study. Self-administered questionnaires addressed lifestyle, sports participation, physical activity, physical fitness perception, and PHC. Results Female gender (OR = 1.92; 95% CI = 1.57–2.35), smoking (OR = 1.31; 95%PI = 1.01–1.68), alcohol consumption (OR = 1.60; 95%PI = 1.30–1.97), unhealthy foods (OR = 1.14; 95%PI = 1.04–1.26), hours of internet use (OR = 1.14; 95%PI = 1.07–1.21), and poor personal fitness perception (OR = 1.60; 95% CI = 1.27–2.02) were associated with PHC in adolescents. Lower physical activity and self-perceived insufficient physical activity, perception of physical fitness as being poor, and not participating in sports were associated with greater somatic and psychological complaints controlling for age, gender, and BMI. Participation in sports and physical activity did not change PHC in adolescents involved in unhealthy behaviour. However, a positive perception of one’s own physical activity and physical fitness decreased PHC in adolescents who reported an unhealthy lifestyle. Conclusions Adolescents demonstrating poorer health-related behavioural profiles showed higher PHC. Physical activity and sports participation were related to lower PHC. Positive physical activity and physical fitness perception changed the associations between PHC and unhealthy lifestyle: adolescents perceiving themselves as sufficiently physically active and those evaluating their physical fitness as good showed lower PHC, despite the presence of unhealthy habits (high screen time, drinking alcohol, smoking, and consuming unhealthy foods). It is important to study cognitive factors when exploring the associations between adolescent lifestyles and PHC. These results are important for health promotion and education programmes aimed at improving healthy lifestyle and psychosocial well-being in adolescents. Electronic supplementary material The online version of this article (10.1186/s12889-019-7311-2) contains supplementary material, which is available to authorized users.

BackgroundArterial hypertension (AH) is a main risk factor for the risk from cardiovascular (CVD) and stroke mortality. Only few data was published on prevalence, awareness and management of AH in Lithuania. Development of objective approaches to the treatment and control of AH reduces the risk of mortality. The aim of this study was to evaluate time trends, the prevalence, awareness, treatment and control of AH and risk of mortality among Lithuanian urban population aged 45–64 years during the period of 1983–2009.MethodsTime trends of AH and risk of mortality were examined in three MONICA health surveys in 1983, 1986, 1992, and in one health survey according to MONICA protocol in 2002 included randomly recruited of 2,218 men and 2,491 women. AH was defined as systolic blood pressure (BP) ≥140 mmHg and/or diastolic BP of ≥90 mmHg or current use of antihypertensive medication. The main outcome measures were all-cause mortality, mortality from CVD, coronary heart disease (CHD) and stroke. The mean duration of follow-up was 11.8 ± 9.2 years. All survey periods were age standardized to the year 2006 of Kaunas population. The estimates of hazard ratio and 95% confidence interval were based on the multivariate Cox proportional hazards regression.ResultsIn men during 1983–2002 period hypertension prevalence was 52.1–58.7% and did not significantly change whereas in women decreased from 61.0 to 51.0%. There was a significant increase in hypertension awareness among hypertensive men and women (45.0 to 64.4% and 47.7 to 72.3%, respectively) and in treated hypertensives (55.4 to 68.3% in men and 65.6 to 86.2% in women). Adjusted Cox proportional hazard regression analyses revealed a strong dose–response association between blood-pressure level and all-cause, CVD, CHD and stroke-mortality risk in both men and women groups.ConclusionIn Lithuanian urban population the prevalence of hypertension remains high. Despite positive changes in hypertension awareness and treatment, hypertension control remains poor. A strong dose–response association between the level of BP and all-cause, CVD, CHD and stroke mortality risk was indicated.

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