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1.  Wealth and Disability in Later Life: The English Longitudinal Study of Ageing (ELSA) 
PLoS ONE  2016;11(11):e0166825.
We examined wealth inequalities in disability, taking into account the effect of both depression and social support among older English adults using data from 5,506 community-dwelling people aged 50 years and over from the English Longitudinal Study of Ageing (ELSA). Disability was measured as self-reported limitations in the Basic Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). Depressive symptomatology was measured using the 8-item Center for Epidemiological Studies-Depression (CES-D) scale. Social support was assessed by marital status and frequency of contact with friends, relatives or children. Multinomial logistic regression models were used to assess the role of social support and depressive symptoms on disability by total household wealth, which is a measure of accumulated assets over the course of life. Our findings showed that the poorest men with disability were more likely to live without a partner and have no weekly contact with children, family or friends compared to the wealthiest. Among women with disability, the poorest were more likely to report loneliness and have no partner while the wealthiest and the intermediate groups were more likely to be living with a partner. There was a strong inverse dose-response association between wealth and depressive symptoms among all participants with disability. This study shows a clear wealth gradient in disability among older English adults, especially for those with elevated depressive symptoms.
doi:10.1371/journal.pone.0166825
PMCID: PMC5119775  PMID: 27875579
2.  Brazil: rapid progress and the challenge of inequality 
doi:10.1186/s12939-016-0465-y
PMCID: PMC5112674  PMID: 27852310
4.  The association of depressive symptoms with cardiovascular and all-cause mortality in Central and Eastern Europe: Prospective results of the HAPIEE study 
Background
Studies in western populations have shown a positive association between depression and cardiovascular disease (CVD) and all-cause mortality. The association with depressive symptoms seems to be graded, rather than limited to the presence versus the absence of depression. Evidence from populations with potentially different patterns of confounders helps to address the consistency of these findings. The objective of the study was to investigate the association between depressive symptoms and all-cause and CVD mortality in populations of Central and Eastern Europe.
Study design
This was a prospective cohort study.
Methods
A total of 24,542 participants aged 45–69 years, randomly selected from populations of Novosibirsk (Russia), Krakow (Poland) and six Czech towns, were included. Depressive symptoms, assessed by the 20-item Center for Epidemiologic Studies Depression (CES-D) scale, were used as both continuous and categorical variables. Data on deaths were obtained from local or national death registers. Associations between depression and mortality were assessed using Cox proportional hazards models.
Results
Over a median of 7 years, 2091 deaths from all causes and 850 CVD deaths occurred in the cohorts. There was a graded association between CES-D score and mortality; the hazard ratio (HR) of CVD mortality for a 1 SD increase in CES-D was 1.20 (95% confidence interval (CI): 1.16–1.24) in men and 1.23 (95% CI: 1.12–1.35) in women; for all-cause mortality, the HRs were 1.13 (95% CI: 1.09–1.18) and 1.17 (95% CI: 1.10–1.25), respectively. The results were similar across countries.
Conclusions
Depressive symptoms predicted CVD and all-cause mortality independently of a wide range of potential confounders. The association followed a gradient and increased mortality risks were associated with scores below the cut-offs that are commonly used to define ‘depression’.
doi:10.1177/2047487316649493
PMCID: PMC5089224  PMID: 27154591
Depressive symptoms; mortality; Eastern Europe; cardiovascular disease
5.  Mortality in Transition: Study Protocol of the PrivMort Project, a multilevel convenience cohort study 
BMC Public Health  2016;16:672.
Background
Previous research using routine data identified rapid mass privatisation as an important driver of mortality crisis following the collapse of Communism in Central and Eastern Europe. However, existing studies on the mortality crisis relying on individual level or routine data cannot assess both distal (societal) and proximal (individual) causes of mortality simultaneously. The aim of the PrivMort Project is to overcome these limitations and to investigate the role of societal factors (particularly rapid mass privatisation) and individual-level factors (e.g. alcohol consumption) in the mortality changes in post-communist countries.
Methods
The PrivMort conducts large-sample surveys in Russia, Belarus and Hungary. The approach is unique in comparing towns that have undergone rapid privatisation of their key industrial enterprises with those that experienced more gradual forms of privatisation, employing a multi-level retrospective cohort design that combines data on the industrial characteristics of the towns, socio-economic descriptions of the communities, settlement-level data, individual socio-economic characteristics, and individuals’ health behaviour. It then incorporates data on mortality of different types of relatives of survey respondents, employing a retrospective demographic approach, which enables linkage of historical patterns of mortality to exposures, based on experiences of family members. By May 2016, 63,073 respondents provided information on themselves and 205,607 relatives, of whom 102,971 had died. The settlement-level dataset contains information on 539 settlements and 12,082 enterprises in these settlements in Russia, 96 settlements and 271 enterprises in Belarus, and 52 settlement and 148 enterprises in Hungary.
Discussion
In addition to reinforcing existing evidence linking smoking, hazardous drinking and unemployment to mortality, the PrivMort dataset will investigate the variation in transition experiences for individual respondents and their families across settlements characterized by differing contextual factors, including industrial characteristics, simultaneously providing information about how excess mortality is distributed across settlements with various privatization strategies.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-016-3249-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12889-016-3249-9
PMCID: PMC4967292  PMID: 27473198
Mortality; Privatization; Post-communist transitions; Multi-level analysis
6.  Society and health of migrants 
doi:10.1007/s10654-016-0174-2
PMCID: PMC4977333  PMID: 27461269
7.  Socioeconomic position in childhood and cancer in adulthood: a rapid-review 
Background
The relationship of childhood socioeconomic position (SEP) to adult cancer has been inconsistent in the literature and there has been no review summarising the current evidence focused solely on cancer outcomes.
Methods and results
We performed a rapid review of the literature, which identified 22 publications from 13 studies, primarily in the UK and northern European countries that specifically analysed individual measures of SEP in childhood and cancer outcomes in adulthood. Most of these studies adjusted for adult SEP as a critical mediator of the relationship of interest.
Conclusions
Results confirm that childhood socioeconomic circumstances have a strong influence on stomach cancer and are likely to contribute, along with adult circumstances, to lung cancer through cumulative exposure to smoking. There was also some evidence of increased risk of colorectal, liver, cervical and pancreatic cancers with lower childhood SEP in large studies, but small numbers of cancer deaths made these estimates imprecise. Gaps in knowledge and potential policy implications are presented.
doi:10.1136/jech-2015-206274
PMCID: PMC4893135  PMID: 26715591
POVERTY; CANCER; SOCIAL INEQUALITIES; POLICY; Health inequalities
8.  Wealth and mortality at older ages: a prospective cohort study 
Background
Despite the importance of socioeconomic position for survival, total wealth, which is a measure of accumulation of assets over the life course, has been underinvestigated as a predictor of mortality. We investigated the association between total wealth and mortality at older ages.
Methods
We estimated Cox proportional hazards models using a sample of 10 305 community-dwelling individuals aged ≥50 years from the English Longitudinal Study of Ageing.
Results
2401 deaths were observed over a mean follow-up of 9.4 years. Among participants aged 50–64 years, the fully adjusted HRs for mortality were 1.21 (95% CI 0.92 to 1.59) and 1.77 (1.35 to 2.33) for those in the intermediate and lowest wealth tertiles, respectively, compared with those in the highest wealth tertile. The respective HRs were 2.54 (1.27 to 5.09) and 3.73 (1.86 to 7.45) for cardiovascular mortality and 1.36 (0.76 to 2.42) and 2.53 (1.45 to 4.41) for other non-cancer mortality. Wealth was not associated with cancer mortality in the fully adjusted model. Similar but less strong associations were observed among participants aged ≥65 years. The use of repeated measurements of wealth and covariates brought about only minor changes, except for the association between wealth and cardiovascular mortality, which became less strong in the younger participants. Wealth explained the associations between paternal occupation at age 14 years, education, occupational class, and income and mortality.
Conclusions
There are persisting wealth inequalities in mortality at older ages, which only partially are explained by established risk factors. Wealth appears to be more strongly associated with mortality than other socioeconomic position measures.
doi:10.1136/jech-2015-206173
PMCID: PMC4819652  PMID: 26511887
SOCIAL INEQUALITIES; MORTALITY; LONGITUDINAL STUDIES; SOCIO-ECONOMIC
9.  Alcohol Consumption and Longitudinal Trajectories of Physical Functioning in Central and Eastern Europe: A 10-Year Follow-up of HAPIEE Study 
Background:
Physical functioning (PF) is an essential domain of older persons’ health and quality of life. Health behaviors are the main modifiable determinants of PF. Cross-sectionally, alcohol consumption appears to be linked to better PF, but longitudinal evidence is mixed and very little is known about alcohol consumption and longitudinal PF trajectories.
Methods:
We conducted longitudinal analyses of 28,783 men and women aged 45–69 years from Novosibirsk (Russia), Krakow (Poland), and seven towns of the Czech Republic. At baseline, alcohol consumption was measured by a graduated frequency questionnaire and problem drinking was evaluated using the CAGE questionnaire. PF was assessed using the Physical Functioning Subscale of the SF-36 instrument at baseline and three subsequent occasions. Growth curve modeling was used to estimate the associations between alcohol consumption and PF trajectories over 10-year follow-up.
Results:
PF scores declined during follow-up in all three cohorts. Faster decline in PF over time was found in Russian female frequent drinkers, Polish female moderate drinkers, and Polish male regular heavy drinkers, in comparison with regular and/or light-to-moderate drinkers. Nondrinking was associated with a faster decline compared with light drinking only in Russian men. Problem drinking and past drinking were not related to the decline rate of PF.
Conclusions:
This large longitudinal study in Central and Eastern European populations with relatively high alcohol intake does not strongly support the existence of a protective effect of alcohol on PF trajectories; if anything, it suggests that alcohol consumption is associated with greater deterioration in PF over time.
doi:10.1093/gerona/glv233
PMCID: PMC4945885  PMID: 26748094
Alcohol consumption; Physical functioning trajectories; Central and Eastern Europe
10.  Austin Powers bites back: a cross sectional comparison of US and English national oral health surveys 
The BMJ  2015;351:h6543.
Objective To compare oral health in the US and England and to assess levels of educational and income related oral health inequalities between both countries.
Design Cross sectional analysis of US and English national surveys.
Setting Non-institutionalised adults living in their own homes.
Participants Oral health measures and socioeconomic indicators were assessed in nationally representative samples: the Adult Dental Health Survey 2009 for England, and the US National Health and Nutrition Examination Survey 2005-08. Adults aged ≥25 years were included in analyses with samples of 8719 (England) and 9786 (US) for analyses by education, and 7184 (England) and 9094 (US) for analyses by income.
Main outcome measures Number of missing teeth, self rated oral health, and oral impacts on daily life were outcomes. Educational attainment and household income were used as socioeconomic indicators. Age standardised estimates of oral health were compared between countries and across educational and income groups. Regression models were fitted, and relative and absolute inequalities were measured using the relative index of inequality (RII) and the slope index of inequality (SII).
Results The mean number of missing teeth was significantly higher in the US (7.31 (standard error 0.15)) than in England (6.97 (0.09)), while oral impacts were higher in England. There was evidence of significant social gradients in oral health in both countries, although differences in oral health by socioeconomic position varied according to the oral health measure used. Consistently higher RII and SII values were found in the US than in England, particularly for self rated oral health. RII estimates for self rated oral health by education were 3.67 (95% confidence interval 3.23 to 4.17) in the US and 1.83 (1.59 to 2.11) in England. In turn, SII values were 42.55 (38.14 to 46.96) in the US and 18.43 (14.01 to 22.85) in England.
Conclusions The oral health of US citizens is not better than the English, and there are consistently wider educational and income oral health inequalities in the US compared with England.
doi:10.1136/bmj.h6543
PMCID: PMC4681766  PMID: 26676027
11.  Mortality risk attributable to smoking, hypertension and diabetes among English and Brazilian older adults (The ELSA and Bambui cohort ageing studies) 
Background: The main aim of this study was to quantify and compare 6-year mortality risk attributable to smoking, hypertension and diabetes among English and Brazilian older adults. This study represents a rare opportunity to approach the subject in two different social and economic contexts. Methods: Data from the data from the English Longitudinal Study of Ageing (ELSA) and the Bambuí Cohort Study of Ageing (Brazil) were used. Deaths in both cohorts were identified through mortality registers. Risk factors considered in this study were baseline smoking, hypertension and diabetes mellitus. Both age–sex adjusted hazard ratios and population attributable risks (PAR) of all-cause mortality and their 95% confidence intervals for the association between risk factors and mortality were estimated using Cox proportional hazards models. Results: Participants were 3205 English and 1382 Brazilians aged 60 years and over. First, Brazilians showed much higher absolute risk of mortality than English and this finding was consistent in all age, independently of sex. Second, as a rule, hazard ratios for mortality to smoking, hypertension and diabetes showed more similarities than differences between these two populations. Third, there was strong difference among English and Brazilians on attributable deaths to hypertension. Conclusions: The findings indicate that, despite of being in more recent transitions, the attributable deaths to one or more risk factors was twofold among Brazilians relative to the English. These findings call attention for the challenge imposed to health systems to prevent and treat non-communicable diseases, particularly in populations with low socioeconomic level.
doi:10.1093/eurpub/ckv225
PMCID: PMC5054267  PMID: 26666869
12.  Alcohol, drinking pattern and all-cause, cardiovascular and alcohol-related mortality in Eastern Europe 
Alcohol has been implicated in the high mortality in Central and Eastern Europe but the magnitude of its effect, and whether it is due to regular high intake or episodic binge drinking remain unclear. The aim of this paper was to estimate the contribution of alcohol to mortality in four Central and Eastern European countries. We used data from the Health, Alcohol and Psychosocial factors in Eastern Europe is a prospective multi-centre cohort study in Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania) and six Czech towns. Random population samples of 34,304 men and women aged 45–69 years in 2002–2005 were followed up for a median 7 years. Drinking volume, frequency and pattern were estimated from the graduated frequency questionnaire. Deaths were ascertained using mortality registers. In 230,246 person-years of follow-up, 2895 participants died from all causes, 1222 from cardiovascular diseases (CVD), 672 from coronary heart disease (CHD) and 489 from pre-defined alcohol-related causes (ARD). In fully-adjusted models, abstainers had 30–50 % increased mortality risk compared to light-to-moderate drinkers. Adjusted hazard ratios (HR) in men drinking on average ≥60 g of ethanol/day (3 % of men) were 1.23 (95 % CI 0.95–1.59) for all-cause, 1.38 (0.95–2.02) for CVD, 1.64 (1.02–2.64) for CHD and 2.03 (1.28–3.23) for ARD mortality. Corresponding HRs in women drinking on average ≥20 g/day (2 % of women) were 1.92 (1.25–2.93), 1.74 (0.76–3.99), 1.39 (0.34–5.76) and 3.00 (1.26–7.10). Binge drinking increased ARD mortality in men only. Mortality was associated with high average alcohol intake but not binge drinking, except for ARD in men.
Electronic supplementary material
The online version of this article (doi:10.1007/s10654-015-0092-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s10654-015-0092-8
PMCID: PMC4756032  PMID: 26467937
Alcohol; Mortality; Eastern Europe; Cardiovascular diseases
13.  English Longitudinal Study of Aging: Can Internet/E-mail Use Reduce Cognitive Decline? 
Background.
Cognitive decline is a major risk factor for disability, dementia, and death. The use of Internet/E-mail, also known as digital literacy, might decrease dementia incidence among the older population. The aim was to investigate whether digital literacy might be associated with decreased cognitive decline in older adulthood.
Methods.
Data from the English Longitudinal Study of Aging cohort with 6,442 participants aged 50–89 years, followed for 8 years, with baseline cognitive testing and four additional time points. The main outcome variable was the relative percentage change in delayed recall from a 10-word-list learning task across five separate measurement points. In addition to digital literacy, socioeconomic variables, including wealth and education, comorbidities, and baseline cognitive function were included in predictive models. The analysis used Generalized Estimating Equations.
Results.
Higher education, no functional impairment, fewer depressive symptoms, no diabetes, and Internet/E-mail use predicted better performance in delayed recall.
Conclusions.
Digital literacy may help reduce cognitive decline among persons aged between 50 and 89 years.
doi:10.1093/gerona/glu105
PMCID: PMC4202262  PMID: 25116923
Cognitive decline; Prevention; Digital literacy; Cohort study; Ageing.
14.  Mother's education and the risk of preterm and small for gestational age birth: a DRIVERS meta-analysis of 12 European cohorts 
Background
A healthy start to life is a major priority in efforts to reduce health inequalities across Europe, with important implications for the health of future generations. There is limited combined evidence on inequalities in health among newborns across a range of European countries.
Methods
Prospective cohort data of 75 296 newborns from 12 European countries were used. Maternal education, preterm and small for gestational age births were determined at baseline along with covariate data. Regression models were estimated within each cohort and meta-analyses were conducted to compare and measure heterogeneity between cohorts.
Results
Mother's education was linked to an appreciable risk of preterm and small for gestational age (SGA) births across 12 European countries. The excess risk of preterm births associated with low maternal education was 1.48 (1.29 to 1.69) and 1.84 (0.99 to 2.69) in relative and absolute terms (Relative/Slope Index of Inequality, RII/SII) for all cohorts combined. Similar effects were found for SGA births, but absolute inequalities were greater, with an SII score of 3.64 (1.74 to 5.54). Inequalities at birth were strong in the Netherlands, the UK, Sweden and Spain and marginal in other countries studied.
Conclusions
This study highlights the value of comparative cohort analysis to better understand the relationship between maternal education and markers of fetal growth in different settings across Europe.
doi:10.1136/jech-2014-205387
PMCID: PMC4552914  PMID: 25911693
EPIDEMIOLOGY; CHILD HEALTH; INEQUALITIES
15.  Job Strain as a Risk Factor for Type 2 Diabetes: A Pooled Analysis of 124,808 Men and Women 
Diabetes Care  2014;37(8):2268-2275.
OBJECTIVE
The status of psychosocial stress at work as a risk factor for type 2 diabetes is unclear because existing evidence is based on small studies and is subject to confounding by lifestyle factors, such as obesity and physical inactivity. This collaborative study examined whether stress at work, defined as “job strain,” is associated with incident type 2 diabetes independent of lifestyle factors.
RESEARCH DESIGN AND METHODS
We extracted individual-level data for 124,808 diabetes-free adults from 13 European cohort studies participating in the IPD-Work Consortium. We measured job strain with baseline questionnaires. Incident type 2 diabetes at follow-up was ascertained using national health registers, clinical screening, and self-reports. We analyzed data for each study using Cox regression and pooled the study-specific estimates in fixed-effect meta-analyses.
RESULTS
There were 3,703 cases of incident diabetes during a mean follow-up of 10.3 years. After adjustment for age, sex, and socioeconomic status (SES), the hazard ratio (HR) for job strain compared with no job strain was 1.15 (95% CI 1.06–1.25) with no difference between men and women (1.19 [1.06–1.34] and 1.13 [1.00–1.28], respectively). In stratified analyses, job strain was associated with an increased risk of diabetes among those with healthy and unhealthy lifestyle habits. In a multivariable model adjusted for age, sex, SES, and lifestyle habits, the HR was 1.11 (1.00–1.23).
CONCLUSIONS
Findings from a large pan-European dataset suggest that job strain is a risk factor for type 2 diabetes in men and women independent of lifestyle factors.
doi:10.2337/dc13-2936
PMCID: PMC4113178  PMID: 25061139
16.  Adiposity, Obesity, and Arterial Aging 
Hypertension  2015;66(2):294-300.
Supplemental Digital Content is available in the text.
We sought to determine whether adiposity in later midlife is an independent predictor of accelerated stiffening of the aorta. Whitehall II study participants (3789 men; 1383 women) underwent carotid-femoral applanation tonometry at the mean age of 66 and again 4 years later. General adiposity by body mass index, central adiposity by waist circumference and waist:hip ratio, and fat mass percent by body impedance were assessed 5 years before and at baseline. In linear mixed models adjusted for age, sex, ethnicity, and mean arterial pressure, all adiposity measures were associated with aortic stiffening measured as increase in pulse wave velocity (PWV) between baseline and follow-up. The associations were similar in the metabolically healthy and unhealthy, according to Adult Treatment Panel-III criteria excluding waist circumference. C-reactive protein and interleukin-6 levels accounted for part of the longitudinal association between adiposity and PWV change. Adjusting for chronic disease, antihypertensive medication and risk factors, standardized effects of general and central adiposity and fat mass percent on PWV increase (m/s) were similar (0.14, 95% confidence interval: 0.05–0.24, P=0.003; 0.17, 0.08–0.27, P<0.001; 0.14, 0.05–0.22, P=0.002, respectively). Previous adiposity was associated with aortic stiffening independent of change in adiposity, glycaemia, and lipid levels across PWV assessments. We estimated that the body mass index–linked PWV increase will account for 12% of the projected increase in cardiovascular risk because of high body mass index. General and central adiposity in later midlife were strong independent predictors of aortic stiffening. Our findings suggest that adiposity is an important and potentially modifiable determinant of arterial aging.
doi:10.1161/HYPERTENSIONAHA.115.05494
PMCID: PMC4490910  PMID: 26056335
aging; arterial stiffness; epidemiology; obesity; longitudinal studies
17.  HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials 
Swerdlow, Daniel I | Preiss, David | Kuchenbaecker, Karoline B | Holmes, Michael V | Engmann, Jorgen E L | Shah, Tina | Sofat, Reecha | Stender, Stefan | Johnson, Paul C D | Scott, Robert A | Leusink, Maarten | Verweij, Niek | Sharp, Stephen J | Guo, Yiran | Giambartolomei, Claudia | Chung, Christina | Peasey, Anne | Amuzu, Antoinette | Li, KaWah | Palmen, Jutta | Howard, Philip | Cooper, Jackie A | Drenos, Fotios | Li, Yun R | Lowe, Gordon | Gallacher, John | Stewart, Marlene C W | Tzoulaki, Ioanna | Buxbaum, Sarah G | van der A, Daphne L | Forouhi, Nita G | Onland-Moret, N Charlotte | van der Schouw, Yvonne T | Schnabel, Renate B | Hubacek, Jaroslav A | Kubinova, Ruzena | Baceviciene, Migle | Tamosiunas, Abdonas | Pajak, Andrzej | Topor-Madry, Romanvan | Stepaniak, Urszula | Malyutina, Sofia | Baldassarre, Damiano | Sennblad, Bengt | Tremoli, Elena | de Faire, Ulf | Veglia, Fabrizio | Ford, Ian | Jukema, J Wouter | Westendorp, Rudi G J | de Borst, Gert Jan | de Jong, Pim A | Algra, Ale | Spiering, Wilko | der Zee, Anke H Maitland-van | Klungel, Olaf H | de Boer, Anthonius | Doevendans, Pieter A | Eaton, Charles B | Robinson, Jennifer G | Duggan, David | Kjekshus, John | Downs, John R | Gotto, Antonio M | Keech, Anthony C | Marchioli, Roberto | Tognoni, Gianni | Sever, Peter S | Poulter, Neil R | Waters, David D | Pedersen, Terje R | Amarenco, Pierre | Nakamura, Haruo | McMurray, John J V | Lewsey, James D | Chasman, Daniel I | Ridker, Paul M | Maggioni, Aldo P | Tavazzi, Luigi | Ray, Kausik K | Seshasai, Sreenivasa Rao Kondapally | Manson, JoAnn E | Price, Jackie F | Whincup, Peter H | Morris, Richard W | Lawlor, Debbie A | Smith, George Davey | Ben-Shlomo, Yoav | Schreiner, Pamela J | Fornage, Myriam | Siscovick, David S | Cushman, Mary | Kumari, Meena | Wareham, Nick J | Verschuren, W M Monique | Redline, Susan | Patel, Sanjay R | Whittaker, John C | Hamsten, Anders | Delaney, Joseph A | Dale, Caroline | Gaunt, Tom R | Wong, Andrew | Kuh, Diana | Hardy, Rebecca | Kathiresan, Sekar | Castillo, Berta A | van der Harst, Pim | Brunner, Eric J | Tybjaerg-Hansen, Anne | Marmot, Michael G | Krauss, Ronald M | Tsai, Michael | Coresh, Josef | Hoogeveen, Ronald C | Psaty, Bruce M | Lange, Leslie A | Hakonarson, Hakon | Dudbridge, Frank | Humphries, Steve E | Talmud, Philippa J | Kivimäki, Mika | Timpson, Nicholas J | Langenberg, Claudia | Asselbergs, Folkert W | Voevoda, Mikhail | Bobak, Martin | Pikhart, Hynek | Wilson, James G | Reiner, Alex P | Keating, Brendan J | Hingorani, Aroon D | Sattar, Naveed
Lancet  2015;385(9965):351-361.
Summary
Background
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.
Methods
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.
Findings
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).
Interpretation
The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.
Funding
The funding sources are cited at the end of the paper.
doi:10.1016/S0140-6736(14)61183-1
PMCID: PMC4322187  PMID: 25262344
18.  Socioeconomic and Gender Inequalities in Job Dissatisfaction among Japanese Civil Servants: The Roles of Work, Family and Personality Characteristics 
Industrial Health  2014;52(6):498-511.
Abstract: This study examines (1) whether there are employment grade and gender differences in job dissatisfaction and (2) whether work, family, and personality characteristics explain grade and gender differences in job dissatisfaction. The participants were 3,812 civil servants, aged 20–65, working at a local government in Japan. In both males and females, low control, low social support, work-to-family conflict, type A behaviour pattern and negative affectivity were significantly associated with job dissatisfaction. In females, high demands, long work hours and being unmarried were also associated with job dissatisfaction. Among males, in comparison with the highest grade employees, the age-adjusted odds ratio (OR) for job dissatisfaction in the lowest grade employees was 1.90 (95% CI: 1.40–2.59). The grade differences reduced to 1.08 (0.76–1.54) after adjustment for work, family and personality characteristics. Among females, similar grade differences were observed, although the differences were not statistically significant. In comparison with males, the age-adjusted OR in females for job dissatisfaction was 1.32 (1.14–1.52). This gender difference was reduced to 0.95 (0.79–1.14) following adjustment for the other factors. The majority of employees belong to low to middle grades, and female employees have increased. Reducing grade and gender differences in work and family characteristics is needed.
doi:10.2486/indhealth.2014-0068
PMCID: PMC4273018  PMID: 25055848
Affect balance; Employment grade; Job satisfaction; Psychosocial stress; Socioeconomic status (SES); The Japanese civil servants study (the JACS study); Type A behaviour; Work-family balance
19.  Combined impact of smoking and heavy alcohol use on cognitive decline in early old age: Whitehall II prospective cohort study 
The British Journal of Psychiatry  2013;203(2):120-125.
Background
Identifying modifiable risk factors for cognitive decline may inform prevention of dementia.
Aims
To examine the combined impact of cigarette smoking and heavy alcohol consumption on cognitive decline from midlife.
Method
Prospective cohort study (Whitehall II cohort) with three clinical examinations in 1997/99, 2002/04 and 2007/09. Participants were 6473 adults (72% men), mean age 55.76 years (s.d. = 6.02) in 1997/99. Four cognitive tests, assessed three times over 10 years, combined into a global z-score (mean 0, s.d. = 1).
Results
Age-related decline in the global cognitive score was faster in individuals who were smoking heavy drinkers than in non-smoking moderate alcohol drinkers (reference group). The interaction term (P = 0.04) suggested that the combined effects of smoking and alcohol consumption were greater than their individual effects. Adjusting for age, gender, education and chronic diseases, 10-year decline in global cognition was –0.42 z-scores (95% CI –0.45 to –0.39) for the reference group. In individuals who were heavy alcohol drinkers who also smoked the decline was –0.57 z-scores (95% CI –0.67 to –0.48); 36% faster than the reference group.
Conclusions
Individuals who were smokers who drank alcohol heavily had a 36% faster cognitive decline, equivalent to an age-effect of 2 extra years over 10-year follow-up, compared with individuals who were non-smoking moderate drinkers.
doi:10.1192/bjp.bp.112.122960
PMCID: PMC3730115  PMID: 23846998
20.  Levels and distribution of self-rated health in the Kazakh population: results from the Kazakhstan household health survey 2012 
BMC Public Health  2014;14:768.
Background
The high and fluctuating mortality and rising health inequalities in post-Soviet countries have attracted considerable attention. However, there are very few individual-level data on distribution of health outcomes in Central Asian countries of the former Soviet Union. We analysed socioeconomic predictors of two self-rated health outcomes in a national survey in Kazakhstan.
Methods
We used data from the 2012 Kazakhstan Household Health Survey on 12,560 respondents aged 15+. Self-rated health, self-reported worsening of health, and a range of socio-demographic variables were collected in an interview. The self-rated health outcomes were dichotomized and logistic regression was used to estimate their associations with education, income, ownership of a car, second house and computer, marital status, ethnicity and urban/rural residence.
Results
The prevalence of poor/very poor self-rated health was 5.3%, and 11.0% of participants reported worse health compared to 1 year ago. After controlling for age, sex and region, all socio-demographic factors were related to self-rated health. After adjusting for all variables, education and car ownership showed the most consistent effects; the odds ratio of poor health and worsening of health were 0.43 (95% confidence interval 0.32-0.58) and 0.54 (0.44-0.68) for university vs. primary education, respectively, and 0.64 (0.51-0.82) and 0.68 (0.58-0.80) for car ownership, respectively. Unmarried persons, ethnic Russians and urban residents also had increased prevalence of poor health in multivariable models.
Conclusions
Despite the limitations of using subjective health measures, these data suggest strong associations between two measures of self-rated health and a number of socioeconomic characteristics. Future studies and health policy initiatives in Kazakhstan and other Central Asian countries should take social determinants of health into account.
doi:10.1186/1471-2458-14-768
PMCID: PMC4131021  PMID: 25073469
Self-rated health; Socioeconomic factors; Central Asian countries
21.  Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data 
Holmes, Michael V | Dale, Caroline E | Zuccolo, Luisa | Silverwood, Richard J | Guo, Yiran | Ye, Zheng | Prieto-Merino, David | Dehghan, Abbas | Trompet, Stella | Wong, Andrew | Cavadino, Alana | Drogan, Dagmar | Padmanabhan, Sandosh | Li, Shanshan | Yesupriya, Ajay | Leusink, Maarten | Sundstrom, Johan | Hubacek, Jaroslav A | Pikhart, Hynek | Swerdlow, Daniel I | Panayiotou, Andrie G | Borinskaya, Svetlana A | Finan, Chris | Shah, Sonia | Kuchenbaecker, Karoline B | Shah, Tina | Engmann, Jorgen | Folkersen, Lasse | Eriksson, Per | Ricceri, Fulvio | Melander, Olle | Sacerdote, Carlotta | Gamble, Dale M | Rayaprolu, Sruti | Ross, Owen A | McLachlan, Stela | Vikhireva, Olga | Sluijs, Ivonne | Scott, Robert A | Adamkova, Vera | Flicker, Leon | van Bockxmeer, Frank M | Power, Christine | Marques-Vidal, Pedro | Meade, Tom | Marmot, Michael G | Ferro, Jose M | Paulos-Pinheiro, Sofia | Humphries, Steve E | Talmud, Philippa J | Leach, Irene Mateo | Verweij, Niek | Linneberg, Allan | Skaaby, Tea | Doevendans, Pieter A | Cramer, Maarten J | van der Harst, Pim | Klungel, Olaf H | Dowling, Nicole F | Dominiczak, Anna F | Kumari, Meena | Nicolaides, Andrew N | Weikert, Cornelia | Boeing, Heiner | Ebrahim, Shah | Gaunt, Tom R | Price, Jackie F | Lannfelt, Lars | Peasey, Anne | Kubinova, Ruzena | Pajak, Andrzej | Malyutina, Sofia | Voevoda, Mikhail I | Tamosiunas, Abdonas | Maitland-van der Zee, Anke H | Norman, Paul E | Hankey, Graeme J | Bergmann, Manuela M | Hofman, Albert | Franco, Oscar H | Cooper, Jackie | Palmen, Jutta | Spiering, Wilko | de Jong, Pim A | Kuh, Diana | Hardy, Rebecca | Uitterlinden, Andre G | Ikram, M Arfan | Ford, Ian | Hyppönen, Elina | Almeida, Osvaldo P | Wareham, Nicholas J | Khaw, Kay-Tee | Hamsten, Anders | Husemoen, Lise Lotte N | Tjønneland, Anne | Tolstrup, Janne S | Rimm, Eric | Beulens, Joline W J | Verschuren, W M Monique | Onland-Moret, N Charlotte | Hofker, Marten H | Wannamethee, S Goya | Whincup, Peter H | Morris, Richard | Vicente, Astrid M | Watkins, Hugh | Farrall, Martin | Jukema, J Wouter | Meschia, James | Cupples, L Adrienne | Sharp, Stephen J | Fornage, Myriam | Kooperberg, Charles | LaCroix, Andrea Z | Dai, James Y | Lanktree, Matthew B | Siscovick, David S | Jorgenson, Eric | Spring, Bonnie | Coresh, Josef | Li, Yun R | Buxbaum, Sarah G | Schreiner, Pamela J | Ellison, R Curtis | Tsai, Michael Y | Patel, Sanjay R | Redline, Susan | Johnson, Andrew D | Hoogeveen, Ron C | Hakonarson, Hakon | Rotter, Jerome I | Boerwinkle, Eric | de Bakker, Paul I W | Kivimaki, Mika | Asselbergs, Folkert W | Sattar, Naveed | Lawlor, Debbie A | Whittaker, John | Davey Smith, George | Mukamal, Kenneth | Psaty, Bruce M | Wilson, James G | Lange, Leslie A | Hamidovic, Ajna | Hingorani, Aroon D | Nordestgaard, Børge G | Bobak, Martin | Leon, David A | Langenberg, Claudia | Palmer, Tom M | Reiner, Alex P | Keating, Brendan J | Dudbridge, Frank | Casas, Juan P
The BMJ  2014;349:g4164.
Objective To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease.
Design Mendelian randomisation meta-analysis of 56 epidemiological studies.
Participants 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers.
Main outcome measures Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.
Results Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (−0.88 (−1.19 to −0.56) mm Hg), interleukin-6 levels (−5.2% (−7.8 to −2.4%)), waist circumference (−0.3 (−0.6 to −0.1) cm), and body mass index (−0.17 (−0.24 to −0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)).
Conclusions Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.
doi:10.1136/bmj.g4164
PMCID: PMC4091648  PMID: 25011450
22.  Alcohol consumption and physical functioning among middle-aged and older adults in Central and Eastern Europe: Results from the HAPIEE study 
Age and Ageing  2014;44(1):84-89.
Background: light-to-moderate drinking is apparently associated with a decreased risk of physical limitations in middle-aged and older adults.
Objective: to investigate the association between alcohol consumption and physical limitations in Eastern European populations.
Study design: a cross-sectional survey of 28,783 randomly selected residents (45–69 years) in Novosibirsk (Russia), Krakow (Poland) and seven towns of Czech Republic.
Methods: physical limitations were defined as <75% of optimal physical functioning using the Physical Functioning (PF-10) Subscale of the Short-Form-36 questionnaire. Alcohol consumption was assessed by a graduated frequency questionnaire, and problem drinking was defined as ≥2 positive responses on the CAGE questionnaire. In the Russian sample, past drinking was also assessed.
Results: the odds of physical limitations were highest among non-drinkers, decreased with increasing drinking frequency, annual consumption and average drinking quantity and were not associated with problem drinking. The adjusted odds ratio (OR) of physical limitations in non-drinkers versus regular moderate drinkers was 1.61 (95% confidence interval: 1.48–1.75). In the Russian sample with past drinking available, the adjusted OR in those who stopped drinking for health reasons versus continuing drinkers was 3.19 (2.58–3.95); ORs in lifetime abstainers, former drinkers for non-health reasons and reduced drinkers for health reasons were 1.27 (1.02–1.57), 1.48 (1.18–1.85) and 2.40 (2.05–2.81), respectively.
Conclusion: this study found an inverse association between alcohol consumption and physical limitations. The high odds of physical limitations in non-drinkers can be largely explained by poor health of former drinkers. The apparently protective effect of heavier drinking was partly due to less healthy former heavy drinkers who moved to lower drinking categories.
doi:10.1093/ageing/afu083
PMCID: PMC4255613  PMID: 24982097
ageing; alcohol consumption; Central and Eastern Europe; older people; physical functioning
23.  Social relationships and health related behaviors among older US adults 
BMC Public Health  2014;14:533.
Background
Health behaviors are a key determinant of health and well-being that are influenced by the nature of the social environment. This study examined associations between social relationships and health-related behaviors among a nationally representative sample of older people.
Methods
We analyzed data from three waves (1999–2004) of the US National Health and Nutrition Examination Survey (NHANES). Participants were 4,014 older Americans aged 60 and over. Log-binomial regression models estimated prevalence ratios (PR) for the associations between social relationships and each of the following health behaviors: alcohol use, smoking, physical activity and dental attendance.
Results
Health-compromising behaviors (smoking, heavy drinking and less frequent dental visits) were related to marital status, while physical activity, a health-promoting behavior, was associated with the size of friendship networks. Smoking was more common among divorced/separated (PR = 2.1; 95% CI: 1.6, 2.7) and widowed (PR = 1.7; 95% CI: 1.3, 2.3) respondents than among those married or cohabiting, after adjusting for socio-demographic background. Heavy drinking was 2.6 times more common among divorced/separated and 1.7 times more common among widowed men compared to married/cohabiting men, while there was no such association among women. For women, heavy drinking was associated with being single (PR = 1.7; 95% CI: 1.0, 2.9). Being widowed was related to a lower prevalence of having visited a dentist compared to being married or living with a partner (PR = 0.92; 95% CI 0.86, 0.99). Those with a larger circle of friends were more likely to be physically active (PR = 1.17; 95% CI:1.06, 1.28 for 5–8 versus less than 5 friends).
Conclusions
Social relationships of older Americans were independently associated with different health-related behaviors, even after adjusting for demographic and socioeconomic determinants. Availability of emotional support did not however mediate these associations. More research is needed to assess if strengthening social relationships would have a significant impact on older people’s health behaviors and ultimately improve their health.
doi:10.1186/1471-2458-14-533
PMCID: PMC4046043  PMID: 24885507
Social relationships; Health behaviors; Aging
24.  Glycemia, Insulin Resistance, Insulin Secretion, and Risk of Depressive Symptoms in Middle Age 
Diabetes Care  2013;36(4):928-934.
OBJECTIVE
The extent to which abnormal glucose metabolism increases the risk of depression remains unclear. In this study, we investigated prospective associations of levels of fasting glucose and fasting insulin and indices of insulin resistance and secretion with subsequent new-onset depressive symptoms (DepS).
RESEARCH DESIGN AND METHODS
In this prospective cohort study of 3,145 adults from the Whitehall II Study (23.5% women, aged 60.6 ± 5.9 years), baseline examination included fasting glucose and insulin level, the homeostasis model assessment of insulin resistance (HOMA2-%IR), and the homeostasis model assessment of β-cell insulin secretion (HOMA2-%B). DepS (Center for Epidemiologic Studies Depression Scale ≥16 or use of antidepressive drugs) were assessed at baseline and at 5-year follow-up.
RESULTS
Over the 5-year follow-up, DepS developed in 142 men and 84 women. Women in the lowest quintile of insulin secretion (HOMA2-%B ≤55.3%) had 2.18 (95% CI 1.25–3.78) times higher odds of developing DepS than those with higher insulin secretion. This association was not accounted for by inflammatory markers, cortisol secretion, or menopausal status and hormone replacement therapy. Fasting insulin measures were not associated with DepS in men, and fasting glucose measures were not associated with new-onset DepS in either sex.
CONCLUSIONS
Low insulin secretion appears to be a risk factor for DepS in middle-aged women, although further work is required to confirm this finding.
doi:10.2337/dc12-0239
PMCID: PMC3609527  PMID: 23230097
25.  Prevalence and Predictors of Carotid Wall Triple Line Pattern in a General Population Sample 
Objective
Carotid intima-media thickness (IMT) and plaques are markers of atherosclerosis and predict cardiovascular events. A specific sonographic triple line pattern (TLP) of the carotid wall has been identified in different conditions, but its origin and clinical significance are unclear. We examined the prevalence and predictors of TLP in a general population.
Methods and Results
The study was conducted in random sample of the general population of Novosibirsk, Russia, within the international Health, Alcohol and Psychosocial Factors in Eastern Europe project. In a subsample of 418 men (aged 45 to 69), carotid IMT, the presence of atherosclerotic plaques, and the presence of TLP were assessed by ultrasound. The prevalence of TLP was 21%. It was associated with IMT (odds ratio=9.53 per 1 SD, P<0.001) and the presence of plaques (odds ratio=2.42, P=0.002). Other predictors of TLP in multivariate models included age, systolic blood pressure, total cholesterol, and smoking. In addition, infrequent consumption of high amounts of alcohol approximately doubled the risk of triple pattern.
Conclusion
Our findings showed high prevalence of TLP of carotid wall in a general male population sample from a typical Russian city. This sonographic pattern was strongly associated with cardiovascular risk factors and diseases, bioimaging indicators of atherosclerosis, and episodic heavy drinking.
doi:10.1161/ATVBAHA.110.218057
PMCID: PMC3951865  PMID: 21493889
alcohol; carotid arteries; Doppler ultrasound; risk factors; intima-media thickness

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