Effects of four different antihypertensive drugs on plasma metabolomic profiles in patients with essential hypertension

Objective In order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured > 600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles. Methods Metabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry. Full metabolomic signatures (the drug cycles and the mean of the 3 placebo cycles) became available in 38 to 42 patients for each drug. Blood pressure was monitored by 24-h recordings. Results Amlodipine (P values down to 0.002), bisoprolol (P values down to 2 x 10(-5)) and losartan (P values down to 2 x 10(-4)) consistently decreased the circulating levels of long-chain acylcarnitines. Bisoprolol tended to decrease (P values down to 0.002) the levels of several medium-and long-chain fatty acids. Hydrochlorothiazide administration was associated with an increase of plasma uric acid level (P = 5 x 10(-4)) and urea cycle metabolites. Decreases of both systolic (P = 0.06) and diastolic (P = 0.04) blood pressure after amlodipine administration tended to associate with a decrease of plasma hexadecanedioate, a dicarboxylic fatty acid recently linked to blood pressure regulation. Conclusions Although this systematic metabolomics study failed to identify circulating metabolites convincingly predicting favorable antihypertensive response to four different drug classes, it provided accumulating evidence linking fatty acid metabolism to human hypertension.Peer reviewe

The Association Between Smoke-Free School Policies and Adolescents’ Perceived Antismoking Norms: Moderation by School Connectedness

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.BACKGROUND: Many European schools implement smoke-free school policies (SFSPs). SFSPs may decrease adolescent smoking by causing adolescents to perceive stronger anti-smoking norms, yet there exists no quantitative evidence that indicates for which norms and for whom such effects may occur. This study therefore assessed to what extent adolescents' perceived anti-smoking norms among best friends, teachers, and society at large were associated with SFSPs, and whether these associations were moderated by adolescents' level of school connectedness. METHODS: Survey data were collected in 2016/2017 on 10,653 14-16-year-old adolescents and 315 staff members in 55 schools from seven European cities. Associations of adolescent-perceived SFSPs and staff-reported SFSPs with best friend, teacher and societal anti-smoking norms were estimated in multilevel logistic regression models, adjusted for demographics and school-level smoking prevalence. We tested for interaction between school connectedness and SFSPs. RESULTS: Adolescent-perceived SFSPs were positively associated with anti-smoking norms by teachers (OR:1.46, 95%CI:1.15-1.85), were negatively associated with anti-smoking norms by best friends (OR:0.81, 95%CI:0.67-0.99), but were not significantly associated with anti-smoking norms by society at large (OR:0.87, 95%CI:0.74-1.02). All interaction tests between adolescent-perceived SFSPs and school connectedness were non-significant. Staff-reported SFSPs were not associated with any norm and showed no significant interaction with school connectedness. CONCLUSIONS: We found that SFSPs are associated with adolescents' perception of more anti-smoking norms by teachers, but less anti-smoking norms by best friends, irrespective of adolescents' level of school connectedness. IMPLICATIONS: Smoke-free school policies, just as many other tobacco control policies, are assumed to foster adolescents' perception of anti-smoking norms. Still, current evidence does not demonstrate which anti-smoking norms may be influenced by SFSPs and whether this influence is equal for adolescents with different levels of school connectedness. This study suggests that SFSPs foster adolescents' perception of anti-smoking norms by teachers, but may concurrently lead to the perception of less anti-smoking norms by best friends, irrespective of adolescents' school connectedness. SFSPs may therefore need to be complemented with interventions that target anti-smoking norms in adolescent peer groups.authorsversionpublishe

Time trends in socioeconomic differences in incidence rates of cancers of gastro-intestinal tract in Finland

BACKGROUND: The magnitude of socioeconomic differences in health varies between societies, and over time within a given society. We studied the association between social class and incidence of cancers of the gastro-intestinal tract over time in a large cohort in Finland. METHODS: We studied social class variation among 45–69 year-old Finns during 1971–95 in incidence of cancers of the gastro-intestinal tract by means of a computerized record linkage of the Finnish Cancer Registry and the 1970 Population Census, which included social class data. RESULTS: There were 2.3 million individuals in the cohort under follow-up, with 1622 cases of cancer of the esophagus, 8069 stomach (non-cardia), 1116 cardia, 408 small intestine, 6361 colon, 5274 rectum, 1616 liver, 1756 gallbladder, and 5084 pancreas during 1971–1995. Cancers of the esophagus, stomach, cardia, gallbladder and pancreas were most common among persons belonging to a low social class. Cancers of the small intestine in males only, colon in both genders, and rectum in females were most common in the higher social classes. Incidence of stomach cancer decreased and incidence of colon cancer increased over time in both genders in all social classes, and the large differences between social classes remained unchanged over time. Incidence rates of cardia cancer did not change substantially over time. CONCLUSION: There is a large variation in incidence of cancer of the gastrointestinal tract by social class in Finland. Although much of the observed social class differences probably could be explained by known etiological factors such as diet, physical exercise, alcohol consumption, smoking and exogenous hormone use, part of the variation is apparently attributable to largely unknown factors

Social mobility and health related behaviours in young people

STUDY OBJECTIVE: To assess the influences related to social mobility, particularly health related behaviours, as one potential explanation for the social class variation in health among adults. DESIGN: The study is based on questionnaire data from the Adolescent Health and Lifestyle Surveys of 1985, 1987, and 1989. SETTING: The whole of Finland. PARTICIPANTS: A representative sample of 8355 adolescents. The response rate was 79%. MEASUREMENT AND MAIN RESULTS: The relation between social mobility and health related behaviours among 16 and 18 year old young people was studied. The measure of social mobility was based on a combination of the social class of origin and achieved social position measured by the present educational status, educational attainment, and labour market position. Three mobility groups were constructed: the downwardly mobile, the upwardly mobile and the stable. Health related behaviours in an upwardly or downwardly mobile group were compared with a stable group from the same social class of origin by calculating relative risks (RR). RRs were assessed by calculating age and sex adjusted rate ratios approximating a Mantel-Haenszel estimate. In logistic regression analyses the independent effects of the social class of origin and the achieved social position were investigated. Most of the nine behaviours studied (smoking, alcohol use, heavy intoxication, coffee drinking, tooth brushing, consumption of sweets, lack of physical exercise, choice of bread spread, and consumption of milk) were related to the direction of mobility so that health compromising behaviours were more frequent among downwardly mobile and less frequent among upwardly mobile young people than their stable peers. Achieved social position proved to determine health related behaviours more strongly than class of origin, thus emphasising the way education facilitates both health values and behaviours as well as the future social position. CONCLUSIONS: The close relation between social mobility and health related behaviours is concluded to be a part of an explanation of social class differences in health observed among adults.

Strategies and barriers to achieving the goal of Finland's tobacco endgame.

ObjectivesFinland boldly legislated the end of tobacco use in its 2010 Tobacco Act, and subsequently expanded the goal in 2016 to eradicate other nicotine-containing products. This study explored stakeholders' perceptions about the strengths, barriers, solutions and rationale for Finland's comprehensive but conventional strategy to achieve its nicotine-free goal.DesignStudy participants were selected based on expertise in policy or practice of tobacco control (n=32). Semi-structured interviews, conducted in 2017 and 2018, covered topics ranging from consensus among stakeholders to Finland's ranking on the 2016 Tobacco Control Scale. The framework method was chosen for analysing interview transcripts.ResultsA perceived strength of Tobacco-Free Finland 2030 was the consensus and cooperation among members of the tobacco control community. The objective of becoming a nicotine- versus smoke-free society had almost unanimous support, challenged by a small minority who argued for greater discussion of harm reduction approaches. The need for maintaining legitimacy and historical successes in tobacco control were reasons for using a conventional strategy. Barriers to achieving the endgame goal included insufficient funding and over-reliance on non-governmental organisations, political/legal constraints, impact of institutional practices on tobacco disparities, ambivalence about the role of mass media and lack of prioritising smoking cessation.ConclusionsStakeholders' broad confidence in reaching the goal of Finland's tobacco endgame suggests that future policy initiatives will reflect the current, conventional strategy. If the Finnish government chooses to continue this approach, then it should designate separate funds for Tobacco-Free Finland 2030 and implement structural changes that will facilitate tobacco control initiatives