Pia Horvat

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

Background Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). Methods and results We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification. Conclusions In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.

Life Course Socioeconomic Position and Mid-Late Life Cognitive Function in Eastern Europe

Objectives. To investigate whether the positive relation between socioeconomic position (SEP) across the life course and later life cognitive function observed in Western populations exists in former communist countries with apparently smaller income inequalities. Method. Structural equation modeling analysis of cross-sectional data on 30,846 participants aged 45–78 years in four Central and Eastern European centers: Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania), and six Czech towns from the HAPIEE (Health, Alcohol, and Psychosocial factors In Eastern Europe) study. SEP was measured using self-reported childhood (maternal education, household amenities), adult (education), and older adult (current material circumstances) indicators. Latent variable for cognition was constructed from word recall, animal naming, and letter search. Results. Associations between SEP measures over the life course and cognition were similar across study centers. Education had the strongest direct association with cognition, followed by current material circumstances. Indirect path from education to cognition, mediated by current SEP, was small. Direct path from mother’s education to cognition was significant but modest, and partially mediated by later SEP measures, particularly education. Discussion. In these Eastern European populations, late life cognition reflected life course socioeconomic trajectories similarly to findings in Western countries.

Alcohol consumption, drinking patterns, and cognitive function in older Eastern European adults

Objective: To investigate associations of frequency, quantity, binge, and problem drinking with cognitive function in older Eastern European adults. Methods: The investigation included 14,575 participants, aged 47 to 78 years at cognitive assessment in 2006–2008 from Novosibirsk (Russia), Krakow (Poland), and 6 Czech towns participating in the HAPIEE (Health, Alcohol, and Psychosocial Factors in Eastern Europe) prospective cohort study. Average response rates were 59% at baseline (2002–2005) and 63% in 2006–2008. Alcohol consumption was assessed at baseline and in 2006–2008. Cognitive tests included immediate and delayed word recall, semantic fluency (animal naming), and letter cancellation. Associations between alcohol indices and cognitive scores were analyzed cross-sectionally (all measures from 2006 to 2008) and prospectively (alcohol and covariates from 2002 to 2005 and cognition from 2006 to 2008). Results: In cross-sectional analyses, nondrinkers had lower cognitive scores and female moderate drinkers had better cognitive performance than light drinkers. Heavy, binge, and problem drinking were not consistently associated with cognitive function. Few associations were replicated in prospective analyses. Participants who stopped drinking during follow-up had worse cognition than stable drinkers; in men, regression coefficients (95% confidence interval) ranged from −0.26 (−0.36, −0.16) for immediate recall to −0.14 (−0.24, −0.04) for fluency. Conclusion: Regular and episodic heavy drinking were not consistently associated with cognitive function. Worse cognition in participants who stopped drinking during follow-up suggests that inclusion of less healthy ex-drinkers may partly explain poorer cognition in nondrinkers.

Alcohol consumption and cognitive performance: a Mendelian randomization study

Aims To use Mendelian randomization to assess whether alcohol intake was causally associated with cognitive function. Design Mendelian randomization using a genetic variant related to alcohol intake (ADH1B rs1229984) was used to obtain unbiased estimates of the association between alcohol intake and cognitive performance. Setting Europe. Participants More than 34 000 adults. Measurements Any versus no alcohol intake and units of intake in the previous week was measured by questionnaire. Cognitive function was assessed in terms of immediate and delayed word recall, verbal fluency and processing speed. Findings Having consumed any versus no alcohol was associated with higher scores by 0.17 standard deviations (SD) [95% confidence interval (CI) = 0.15, 0.20] for immediate recall, 0.17 SD (95% CI = 0.14, 0.19) for delayed recall, 0.17 SD (95% CI = 0.14, 0.19) for verbal fluency and 0.12 SD (95% CI = 0.09, 0.15) for processing speed. The minor allele of rs1229984 was associated with reduced odds of consuming any alcohol (odds ratio = 0.87; 95% CI = 0.80, 0.95; P = 0.001; R2 = 0.1%; F-statistic = 47). In Mendelian randomization analysis, the minor allele was not associated with any cognitive test score, and instrumental variable analysis suggested no causal association between alcohol consumption and cognition: −0.74 SD (95% CI = −1.88, 0.41) for immediate recall, −1.09 SD (95% CI = −2.38, 0.21) for delayed recall, −0.63 SD (95% CI = −1.78, 0.53) for verbal fluency and −0.16 SD (95% CI = −1.29, 0.97) for processing speed. Conclusions The Mendelian randomization analysis did not provide strong evidence of a causal association between alcohol consumption and cognitive ability.

Mortality in Transition: Study Protocol of the PrivMort Project, a multilevel convenience cohort study

BackgroundPrevious 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.MethodsThe 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.DiscussionIn 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.

The effect of rapid privatisation on mortality in mono-industrial towns in post-Soviet Russia: a retrospective cohort study

Summary Background Population-level data suggest that economic disruptions in the early 1990s increased working-age male mortality in post-Soviet countries. This study uses individual-level data, using an indirect estimation method, to test the hypothesis that fast privatisation increased mortality in Russia. Methods In this retrospective cohort study, we surveyed surviving relatives of individuals who lived through the post-communist transition to retrieve demographic and socioeconomic characteristics of their parents, siblings, and male partners. The survey was done within the framework of the European Research Council (ERC) project PrivMort (The Impact of Privatization on the Mortality Crisis in Eastern Europe). We surveyed relatives in 20 mono-industrial towns in the European part of Russia (ie, the landmass to the west of the Urals). We compared ten fast-privatised and ten slow-privatised towns selected using propensity score matching. In the selected towns, population surveys were done in which respondents provided information about vital status, sociodemographic and socioeconomic characteristics and health-related behaviours of their parents, two eldest siblings (if eligible), and first husbands or long-term partners. We calculated indirect age-standardised mortality rates in fast and slow privatised towns and then, in multivariate analyses, calculated Poisson proportional incidence rate ratios to estimate the effect of rapid privatisation on all-cause mortality risk. Findings Between November, 2014, and March, 2015, 21 494 households were identified in 20 towns. Overall, 13 932 valid interviews were done (with information collected for 38 339 relatives [21 634 men and 16 705 women]). Fast privatisation was strongly associated with higher working-age male mortality rates both between 1992 and 1998 (age-standardised mortality ratio in men aged 20–69 years in fast vs slow privatised towns: 1·13, SMR 0·83, 95% CI 0·77–0·88 vs 0·73, 0·69–0·77, respectively) and from 1999 to 2006 (1·15, 0·91, 0·86–0·97 vs 0·79, 0·75–0·84). After adjusting for age, marital status, material deprivation history, smoking, drinking and socioeconomic status, working-age men in fast-privatised towns experienced 13% higher mortality than in slow-privatised towns (95% CI 1–26). Interpretation The rapid pace of privatisation was a significant factor in the marked increase in working-age male mortality in post-Soviet Russia. By providing compelling evidence in support of the health benefits of a slower pace of privatisation, this study can assist policy makers in making informed decisions about the speed and scope of government interventions. Funding The European Research Council.

Serum folate, vitamin B-12 and cognitive function in middle and older age: The HAPIEE study

Background Nutrient status of B vitamins, particularly folate and vitamin B-12, may be related to cognitive ageing but epidemiological evidence remains inconclusive. Objective The aim of this study was to estimate the association of serum folate and vitamin B-12 concentrations with cognitive function in middle-aged and older adults from three Central and Eastern European populations. Methods Men and women aged 45–69 at baseline participating in the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study were recruited in Krakow (Poland), Kaunas (Lithuania) and six urban centres in the Czech Republic. Tests of immediate and delayed recall, verbal fluency and letter search were administered at baseline and repeated in 2006–2008. Serum concentrations of biomarkers at baseline were measured in a sub-sample of participants. Associations of vitamin quartiles with baseline (n = 4166) and follow-up (n = 2739) cognitive domain-specific z-scores were estimated using multiple linear regression. Results After adjusting for confounders, folate was positively associated with letter search and vitamin B-12 with word recall in cross-sectional analyses. In prospective analyses, participants in the highest quartile of folate had higher verbal fluency (p < 0.01) and immediate recall (p < 0.05) scores compared to those in the bottom quartile. In addition, participants in the highest quartile of vitamin B-12 had significantly higher verbal fluency scores (β = 0.12; 95% CI = 0.02, 0.21). Conclusions Folate and vitamin B-12 were positively associated with performance in some but not all cognitive domains in older Central and Eastern Europeans. These findings do not lend unequivocal support to potential importance of folate and vitamin B-12 status for cognitive function in older age. Long-term longitudinal studies and randomised trials are required before drawing conclusions on the role of these vitamins in cognitive decline.

Smoking and mortality in Eastern Europe: results from the PrivMort retrospective cohort study of 177,376 individuals

Background The estimated prevalence of smoking and proportion of deaths due to tobacco in Eastern European countries are among the highest in the world. Existing estimates of mortality attributable to smoking in the region are mostly indirect. The aim of this analysis was to calculate the proportion of tobacco-attributed deaths in three Eastern European countries using individual level cohort data. Methods The PrivMort project established a cohort of relatives of participants in population sample surveys in Russia, Belarus and Hungary. Survey participants provided data on smoking habits and vital statistics of their close relatives between 1982 and 2013. Population attributable risk fractions (PARF) in men (n = 99528) and women (n = 77848) aged 40-79 years were calculated from the prevalence rates of smoking and hazard ratios of mortality for smokers versus non-smokers. Trends in PARF over four 8-year time periods (1982-1989, 1990-1997, 1998-2005, and 2006-2013) were examined. Results In men in the most recent period (2006-2013), the proportions of deaths attributable to tobacco were 23% in Russia, 22% in Belarus, and 22% in Hungary. The respective estimates in women were lower (2%, 2%, and 13%), possibly due to underestimation of smoking prevalence. PARF estimates have declined slightly since the early 1990s in men but increased in women. Conclusions Consistently with existing indirect estimates, our results based on individual level cohort data suggest that over one fifth of all deaths in men aged 40-79 years are attributable to tobacco. While these proportions are lower in women, the increasing trend is a major concern. Implications This is the first large scale, individual-level cohort study that estimated the mortality attributable to tobacco smoking directly in Eastern European population samples. The results confirm previous indirect estimates and show that more than 20% of all deaths in Eastern European men can be attributed to tobacco. The study also confirms the increasing trend in smoking-related deaths among women. These findings emphasize the importance of targeted policy interventions in Eastern European countries.