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1.  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
2.  Health Factors and Risk of All-Cause, Cardiovascular, and Coronary Heart Disease Mortality: Findings from the MONICA and HAPIEE Studies in Lithuania 
PLoS ONE  2014;9(12):e114283.
Aims
This study investigated the trends and levels of the prevalence of health factors, and the association of all-cause and cardiovascular (CVD) mortality with healthy levels of combined risk factors among Lithuanian urban population.
Methods
Data from five general population surveys in Kaunas, Lithuania, conducted between 1983 and 2008 were used. Healthy factors measured at baseline include non-smoking, normal weight, normal arterial blood pressure, normal level of total serum cholesterol, normal physical activity and normal level of fasting glucose. Among 9,209 men and women aged 45–64 (7,648 were free from coronary heart disease (CHD) and stroke at baseline), 1,219 death cases from any cause, 589 deaths from CVD, and 342 deaths from CHD occurred during follow up. Cox proportional hazards regression was used to estimate the association between health factors and mortality from all causes, CVD and CHD.
Results
Between 1983 and 2008, the proportion of subjects with 6 healthy levels of risk factors was higher in 2006–2008 than in 1983–1984 (0.6% vs. 0.2%; p = 0.09), although there was a significant increase in fasting glucose and a decline in intermediate physical activity. Men and women with normal or intermediate levels of risk factors had significantly lower all-cause, CVD and CHD mortality risk than persons with high levels of risk factors. Subjects with 5–6 healthy factors had hazard ratio (HR) of CVD mortality 0.35 (95% confidence interval (CI) 0.15–0.83) compared to average risk in the whole population. The hazard ratio for CVD mortality risk was significant in men (HR 0.34, 95% CI 0.12–0.97) but not in women (HR 0.38, 95% CI 0.09–1.67).
Conclusions
An inverse association of most healthy levels of cardiovascular risk factors with risk of all-cause and CVD mortality was observed in this urban population-based cohort. A greater number of cardiovascular health factors were related with significantly lower risk of CVD mortality, particularly among men.
doi:10.1371/journal.pone.0114283
PMCID: PMC4257606  PMID: 25479610
3.  Trends in Prevalence of Dyslipidaemias and the Risk of Mortality in Lithuanian Urban Population Aged 45–64 in Relation to the Presence of the Dyslipidaemias and the Other Cardiovascular Risk Factors 
PLoS ONE  2014;9(6):e100158.
The aim of this study was to provide reliable information on dyslipidaemias, to estimate the trend of the prevalence of dyslipidaemias and other selected cardiovascular disease (CVD) risk factors at population level, and to evaluate the risk of all-cause and CVD mortality in relation to presence of mixed dyslipidaemias and other CVD risk factors.
Methods
Data from the five surveys (1983–2008) are presented. A random sample of 9,209 subjects aged 45–64 was selected for statistical analysis. During follow-up there were 1653 death cases from any cause, 864 deaths from CVD. Estimates of hazard ratios (HR) and 95% confidence intervals (CI) were based on the multivariate Cox proportional hazards regression for all-cause mortality and CVD mortality.
Results
During 25 year period the prevalence of normal total cholesterol level (<5.2 mmol/L) significantly increased only in women; triglycerides and high density lipoprotein (HDL) cholesterol did not change in men and women. Findings in our longitudinal study showed that in men and women mixed dyslipidaemias (HDL cholesterol <1.03 mmol/L plus triglycerides ≥1.70 mmol/L) significantly increased the risk for all-cause and CVD mortality (respectively in men HR = 1.30; HR = 1.15, in women HR = 1.83; HR = 2.13). These mixed dyslipidaemia combinations combination with the other risk factors such as arterial hypertension, high fasting glucose level increased all-cause and CVD mortality risk in men and women; while, these mixed dyslipidaemias plus smoking increased all-cause and CVD mortality risk only in men compared to never smokers without these dyslipidaemias (respectively HR = 1.89; HR = 1.92); and these dyslipidaemias plus obesity increased all-cause and CVD mortality risk in women (respectively HR = 2.25; HR = 2.39) and CVD mortality risk in men (HR = 1.72), as compared to responders without obesity and these dyslipidaemias.
Conclusion
Mixed dyslipidaemias (reduced HDL cholesterol plus elevated triglycerides) significantly increased the risk for all-cause and CVD mortality in this Lithuanian population aged 45–64 years.
doi:10.1371/journal.pone.0100158
PMCID: PMC4067295  PMID: 24955583
4.  Does Inclusion of Education and Marital Status Improve SCORE Performance in Central and Eastern Europe and Former Soviet Union? Findings from MONICA and HAPIEE Cohorts 
PLoS ONE  2014;9(4):e94344.
Background and Objective
The SCORE scale predicts the 10-year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk version of SCORE is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), due to high CVD mortality rates in these countries. Given the pronounced social gradient in cardiovascular mortality in the region, it is important to consider social factors in the CVD risk prediction. We investigated whether adding education and marital status to SCORE benefits its prognostic performance in two sets of population-based CEE/FSU cohorts.
Methods
The WHO MONICA (MONItoring of trends and determinants in CArdiovascular disease) cohorts from the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s (577 atherosclerotic CVD deaths among 14,969 participants with non-missing data). The HAPIEE (Health, Alcohol, and Psychosocial factors In Eastern Europe) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002–05 (395 atherosclerotic CVD deaths in 19,900 individuals with non-missing data).
Results
In MONICA and HAPIEE, the high-risk SCORE ≥5% at baseline strongly and significantly predicted fatal CVD both before and after adjustment for education and marital status. After controlling for SCORE, lower education and non-married status were significantly associated with CVD mortality in some samples. SCORE extension by these additional risk factors only slightly improved indices of calibration and discrimination (integrated discrimination improvement <5% in men and ≤1% in women).
Conclusion
Extending SCORE by education and marital status failed to substantially improve its prognostic performance in population-based CEE/FSU cohorts.
doi:10.1371/journal.pone.0094344
PMCID: PMC3979770  PMID: 24714549
5.  Protective effects of angiotensin-converting enzyme I/I and matrix metalloproteinase-3 6A/6A polymorphisms on dilatative pathology within the ascending thoracic aorta 
Objective
Activation of matrix metalloproteinases and the renin/angiotensin signaling pathways is under investigation with regard to their potential pathogenesis in dilatative pathology of the aorta. The purpose of this study was to explore matrix metalloproteinase-3 5A/6A and angiotensin-converting enzyme I/D polymorphisms as predisposing factors to dilatative pathology of the aorta.
Methods
We studied 107 patients who underwent aortic reconstruction surgery due to dilatative pathology of ascending thoracic aorta and a random sample of the population (n =773), all from Lithuania. The insertion/deletion (−1171 5A/6A) polymorphism in the promoter region of matrix metalloproteinase-3 studied by real-time polymerase-chain-reaction amplification and the D and I alleles were identified on the basis of standard polymerase-chain-reaction amplification of the respective fragments from intron 16 of the angiotensin-converting enzyme gene.
Results
The frequency of the angiotensin-converting enzyme D allele was significantly higher in dilatative pathology of ascending thoracic aorta patients than in the reference group subjects (0.55 vs 0.48, respectively). The latter group had a significantly higher frequency of the angiotensin-converting enzyme I/I genotype than in dilatative pathology of ascending thoracic aorta patients (27.4% vs 16.5%, respectively). In the reference group, the frequency of combined angiotensin-converting enzyme I/I and matrix metalloproteinase-3 6A/6A genotypes was 7.5%, while in the dilatative pathology of ascending thoracic aorta patient group, there was no one carrying that combined genotype (p=0.001).
Conclusions
The present study showing a role of angiotensin-converting enzyme and matrix metalloproteinase-3 in the development of dilatative pathology of ascending thoracic aorta permits us to entertain a possible protective mechanism for the combined effects of the angiotensin-converting enzyme I/I and the matrix metalloproteinase-3 6A/6A genotypes.
doi:10.1016/j.ejcts.2010.10.014
PMCID: PMC3968396  PMID: 21111627
Thoracic aorta; Aneurysm; Matrix metalloproteinase-3; Angiotensin-converting enzyme; Polymorphism
6.  Accessibility and use of urban green spaces, and cardiovascular health: findings from a Kaunas cohort study 
Environmental Health  2014;13:20.
Background
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).
Methods
We 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.
Results
We 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).
Conclusion
Our analysis suggests public health policies aimed at promoting healthy lifestyles in urban settings could produce cardiovascular benefits.
doi:10.1186/1476-069X-13-20
PMCID: PMC4000006  PMID: 24645935
Green spaces; Cardiovascular diseases; Risk factors
7.  Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) study: dietary patterns and their association with socio-demographic factors in Lithuanian urban population of Kaunas city 
Objectives
The purpose of this study was to identify the main dietary patterns in Lithuanian urban population and to determine their association with socio-demographic factors.
Methods
Data from the survey performed in the framework of the HAPIEE (Health, Alcohol, Psychosocial factors in Eastern Europe) study were presented. A random sample of 7087 individuals aged 45-72 years was screened in 2006-2008.
Results
Factor analysis of the main dietary patterns revealed five-factor solution which accounted 47.8 % of the variance: “fresh vegetables and fruit” “sweets” “porridge and cereals” “potatoes, meat, boiled vegetables and eggs” “chicken and fish”. “Fresh vegetables and fruits” factor and “sweets” factor were inversely associated with age both in men and women: older people consumed less frequent than average of particular food groups. Dietary patterns of people with good self-rated health and university education were healthier than among people with lower education and poorer health.
Conclusion
Nutrition education efforts should focus on improving food diversity, with particular targeting of lower educated, single, and older people.
doi:10.1007/s00038-010-0170-3
PMCID: PMC3947489  PMID: 20703510
dietary patterns; socio-demographic factors; education; self-rated health
8.  Comparison of four definitions of the metabolic syndrome and odds of ischemic heart disease in the Lithuanian urban population 
Objectives
The purpose of this study was to compare the prevalence of metabolic syndrome diagnosed using four different definitions in the Lithuanian urban population and to determine their association with ischemic heart disease.
Methods
Data from the survey performed in the framework of the HAPIEE (Health, Alcohol, and Psychosocial factors In Eastern Europe) study were presented. A random sample of 7087 individuals aged 45-72 years was screened in 2006-2008.
Results
In Lithuanian urban population of Kaunas city aged 45-72 years, the highest prevalence of metabolic syndrome was determined according to the new Joint Interim Societies (JIS) definition (44.1% of men and 48.7% of women). After adjusting for age, education, smoking habits the metabolic syndrome (irrespective of definition) was associated with a significantly higher risk of ischemic heart disease.
Conclusion
All four metabolic syndrome definitions were associated with ischemic heart disease risk; however odds of this disease were higher in people with metabolic syndrome defined by American Heart Association National Heart Lung Blood Institute definition and National Cholesterol Education program Adult Treatment Panel III definition, than by the new JIS definition.
doi:10.1007/s00038-011-0244-x
PMCID: PMC3947490  PMID: 21384223
metabolic syndrome; odds of ischemic heart disease
9.  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.
doi:10.1093/geronb/gbu014
PMCID: PMC3983917  PMID: 24598045
Cognitive aging; Eastern Europe; Life course; Socioeconomic position.
10.  Correlates of depressive symptoms in urban middle-aged and elderly Lithuanians 
Purpose
The study aimed to examine the prevalence of depressive symptoms and their correlates in urban middle-aged and elderly Lithuanian adults.
Methods
Data from the survey was collected within the framework of the international project HAPIEE (Health, Alcohol and Psychosocial Factors in Eastern Europe). A random sample of 7,115 individuals aged 45–72 years was screened in 2006–2008.
Results
Depressive symptoms were differently associated with independent variables by sex. In men, deprivation (OR 1.85, 95 % CI 1.54–2.17), being divorced (OR 2.34, 95 % CI 1.61–3.39) or widowed (OR 3.64, 95 % CI 2.40–5.52), physical inactivity (OR 1.30, 95 % CI 1.02–1.65), having a history of spine and joint disease (OR 1.72, 95 % CI 1.36–2.17), average perceived health (OR 2.14, 95 % CI 1.55–2.95), poor perceived health (OR 5.13, 95 % CI 3.39–7.76), average quality of life (OR 2.0, 95 % CI 1.55–2.95), or poor quality of life (OR 8.86, 95 % CI 5.19–15.13) were significantly associated with depressive symptoms. In women, deprivation (OR 1.28, 95 % CI 1.15–1.43), being widowed (OR 1.52, 95 % CI 1.23–1.88), mean dose of alcohol per occasion 40–79.9 g (OR 1.65, 95 % CI 1.18–2.30) and more than 80 g (OR 2.09, 95 % CI 1.14–3.82), physical inactivity in leisure time (OR 1.27, 95 % CI 1.04–1.57), having a history of spine and joint disease (OR 1.26, 95 % CI 1.06–1.51), average perceived health (OR 2.56, 95 % CI 1.89–2.72), poor perceived health (OR 5.07, 95 % CI 3.62–7.11), average quality of life (OR 2.27, 95 % CI 1.89–2.72), or poor quality of life (OR 7.21, 95 % CI 4.73–11.00) were significantly associated with depressive symptoms.
Conclusions
Health status and lifestyle factors are associated with depressive symptoms. Associations between depressive symptoms and long-term health problems are partially mediated by self-rated quality of life and self-rated health.
doi:10.1007/s00127-014-0833-0
PMCID: PMC4108842  PMID: 24570202
Depressive symptoms; Health status; Life-style factors; Middle-aged and elderly Lithuanian adults
11.  SCORE performance in Central and Eastern Europe and former Soviet Union: MONICA and HAPIEE results 
European Heart Journal  2013;35(9):571-577.
Aims
The Systematic COronary Risk Evaluation (SCORE) scale assesses 10 year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk SCORE version is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), but its performance has never been systematically assessed in the region. We evaluated SCORE performance in two sets of population-based CEE/FSU cohorts.
Methods and results
The cohorts based on the World Health Organization MONitoring of trends and determinants in CArdiovascular disease (MONICA) surveys in the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s. The Health, Alcohol, and Psychosocial factors in Eastern Europe (HAPIEE) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002–05. In Cox regression analyses, the high-risk SCORE ≥5% at baseline significantly predicted CVD mortality in both MONICA [n = 15 027; hazard ratios (HR), 1.7–6.3] and HAPIEE (n = 20 517; HR, 2.6–10.5) samples. While SCORE calibration was good in most MONICA samples (predicted and observed mortality were close), the risk was underestimated in Russia. In HAPIEE, the high-risk SCORE overpredicted the estimated 10 year mortality for Czech and Polish samples and adequately predicted it for Russia. SCORE discrimination was satisfactory in both MONICA and HAPIEE.
Conclusion
The high-risk SCORE underestimated the fatal CVD risk in Russian MONICA but performed well in most MONICA samples and Russian HAPIEE. This SCORE version might overestimate the risk in contemporary Czech and Polish populations.
doi:10.1093/eurheartj/eht189
PMCID: PMC3938861  PMID: 23786858
Cardiovascular mortality; Cardiovascular risk factors; SCORE risk function; Risk prediction; Central and Eastern Europe; Former Soviet Union
12.  SCARB1 single nucleotide polymorphism (rs5888) is associated with serum lipid profile and myocardial infarction in an age- and gender-dependent manner 
Background
Mutation in SCARB1 gene, exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans though the results have been inconsistent. We analysed the impact of SCARB1 single nucleotide polymorphism (SNP) rs5888 with plasma lipid profile and association with coronary artery disease (CAD) in a Lithuanian population characterized by high morbidity and mortality from CAD and high prevalence of hypercholesterolemia.
Methods
The study included 1976 subjects from a random sample (reference group) and an myocardial infarction (MI) group of 463 patients. Genotyping of SCARB1 (rs5888) was carried out using the real-time polymerase chain reaction method.
Results/principal findings
Analysis of rs5888 C/T gene polymorphism in the reference group revealed that male TT genotype carriers (25–74 years) had significantly higher total cholesterol and triglyceride concentrations (5.70 mmol/l vs. 5.49 mmol/l; p = 0.036, and 1.70 mmol/l vs. 1.40 mmol/l, p = 0.023, respectively) than CT carriers and the oldest males (65–74 years) TT carriers had significantly higher high density lipoprotein cholesterol concentrations in comparison to heterozygous (1.52 mmol/l vs. 1.36 mmol/l, p = 0.033). The youngest female (25–44 years) TT genotype carriers had significantly lower low density lipoprotein cholesterol concentrations in comparison to C homozygous (2.59 mmol/l vs. 2.92 mmol/l, p = 0.023). The frequency of the SCARB1 TT genotype in the oldest male MI group (65–74 years) was significantly lower than in the corresponding reference group subjects (9.4% vs. 22.3%, p = 0.006). SCARB1 TT genotype was associated with decreased odds of MI in males aged 65–75 years (OR = 0.24, 95% CI 0.10-0.56, p = 0.001).
Conclusions/significance
SCARB1 polymorphism is associated with lipid metabolism and CAD in an age- and gender- dependent manner. Analysis of SCARB1 SNP rs5888 C/T genotypes revealed an atheroprotective phenotype of lipid profile in older men and in young women TT genotype carriers in the reference group. SCARB1 TT genotype was associated with decreased odds of MI in aged men.
doi:10.1186/1476-511X-12-24
PMCID: PMC3599926  PMID: 23510561
Coronary artery disease (CAD); Myocardial infarction (MI); Scavenger receptor Class B Type 1 gene (SCARB1); Single nucleotide polymorphism (SNP)
13.  Cardiovascular risk factors and cognitive function in middle aged and elderly Lithuanian urban population: results from the HAPIEE study 
BMC Neurology  2012;12:149.
Background
The purpose of this study was to examine associations between cardiovascular risk factors and cognitive ability in middle aged and elderly Lithuanian urban population.
Methods
Data from the survey performed in the framework of the HAPIEE (Health, Alcohol, Psychosocial Factors in Eastern Europe) study were presented. A random sample of 7,087 individuals aged 45–72 years was screened in 2006–2008.
Results
The scores of immediate recall and delayed verbal recall, cognitive speed and attention were significantly lower in men than in women; yet numerical ability scores were higher in men. Significant associations between lowered cognitive functions and previous stroke (in male OR = 2.52; 95% CI = 1.75-3.64; in female OR = 2.45; 95% CI = 1.75, 3.64) as well as ischemic heart disease history (among male OR = 1.28; 95% CI = 1.03-1.60) have been determined. Higher level of physical activity in leisure time (among female OR = 1.32; 95% CI = 1.03-1.69), poor self-rated health (among male OR = 1.57; 95% CI = 1.15-2.14) and poor quality of life (in male OR = 1.67; 95% CI = 1.07-2.61; in female OR = 2.81; 95% CI = 1.92-4.11) were related to lowered cognitive function.
Conclusions
The findings of the study suggest that associations between cardiovascular risk factors and lowered cognitive function among healthy middle-aged and elderly adults strongly depend on gender.
doi:10.1186/1471-2377-12-149
PMCID: PMC3517768  PMID: 23199035
14.  Alcohol consumption and risk of gastric cancer: a cohort study of men in Kaunas, Lithuania, with up to 30 years follow-up 
BMC Cancer  2012;12:475.
Background
Gastric cancer is the second most common cause of death from cancer in the world. Epidemiological findings on alcohol use in relation to gastric cancer remain controversial. The aim of this study was to examine the effect of alcohol consumption on the risk of gastric cancer.
Methods
The association between alcohol intake and the risk of gastric cancer was examined in a population-based cohort of 7,150 men in Kaunas, Lithuania, who were enrolled during 1972–1974 or 1976–1980. After up to 30 years of follow-up, 185 gastric cancer cases were identified. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). The attained age was used as a time-scale.
Results
After adjustment for smoking, education level and body mass index, the HR of gastric cancer was 2.00 (95% CI: 1.04–3.82) for the highest alcohol consumption frequency (2–7 times per week) compared with occasional drinking (a few times per year) and 1.90 (95% CI: 1.13–3.18) for ≥100.0 g ethanol/week versus 0.1–9.9 g ethanol/week. A stronger effect of alcohol consumption on gastric cancer risk was observed during the second half of the study (1993–2008). In the analysis of gastric cancer risk by alcoholic beverage type, all beverages were included simultaneously in the model. The multivariate HR for men who consumed ≥0.5 litre of wine per occasion (compared with those who consumed <0.5 litre) was 2.95 (95% CI: 1.30–6.68). Higher consumption of beer or vodka was not statistically significantly associated with gastric cancer risk. After adjustment for smoking, education level, body mass index and ethanol, we found no excess risk of gastric cancer in association with total acetaldehyde intake.
Conclusions
This study supports a link between alcohol consumption (primarily from ethanol) and the development of gastric cancer in the Lithuanian population. Although an association with heavy wine consumption was observed, the effect of exposure to acetaldehyde on the development of gastric cancer in this cohort was not confirmed. Further research is needed to provide a more detailed evaluation of alcohol drinking and gastric cancer risk.
doi:10.1186/1471-2407-12-475
PMCID: PMC3527179  PMID: 23066954
Alcohol; Alcoholic beverage; Gastric cancer; Cohort studies; Risk factors
15.  Trends in prevalence, awareness, treatment, and control of hypertension, and the risk of mortality among middle-aged Lithuanian urban population in 1983–2009 
Background
Arterial 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.
Methods
Time 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.
Results
In 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.
Conclusion
In 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.
doi:10.1186/1471-2261-12-68
PMCID: PMC3480954  PMID: 22937997
Hypertension; Awareness; Treatment; Control; Risk of mortality
16.  Socioeconomic circumstances, health behaviours and functional limitations in older persons in four Central and Eastern European populations 
Age and Ageing  2012;41(6):728-735.
Objectives: to investigate functional limitations and their association with socioeconomic factors in four Central and Eastern European populations.
Methods: a cross-sectional study of random population samples in Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania) and six Czech towns participating in the HAPIEE study. Functional limitations (classified into tertiles of the SF-36 physical functioning subscale), socioeconomic circumstances and health behaviours were available for 34,431 subjects aged 45–69 years.
Results: the proportion of subjects in the worst tertile of the functional limitations score (≤80% of the maximum score) ranged from 21% of the men in Kaunas to 48% in Krakow women. In multivariate ordered logistic regression, functional limitations were strongly inversely associated with education and positively with material deprivation and with being economically inactive. Functional limitations were more common in male smokers and less common in alcohol drinkers. Socioeconomic characteristics explained some of the differences in functional limitations between populations. Health behaviours explained some of the differences between social groups in both genders and between populations in women.
Conclusion: unexpectedly, functional limitations were not most common in the sample from Russia, the country with the highest mortality rates. All socioeconomic measures were strongly associated with functional limitations and made some contribution towards explaining differences in limitations between populations.
doi:10.1093/ageing/afs114
PMCID: PMC3476830  PMID: 22923605
disability; physical functioning; socioeconomic factors; Eastern Europe; older people
17.  The Predicted Impact of Heart Disease Prevention and Treatment Initiatives on Mortality in Lithuania, a Middle-Income Country 
Preventing Chronic Disease  2011;8(6):A139.
Introduction
Disease-prevention programs compete with disease-treatment programs for scarce resources. This analysis predicts the impact of heart disease prevention and treatment initiatives for Lithuania, a middle-income Baltic country of 3.3 million people.
Methods
To perform the analysis, we used data from clinical trials, the Lithuanian mortality registry, the Kaunas Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) register, Kaunas University Hospital and, when data from Lithuania were not available, the United States. We used the predicted reduction in all-cause mortality (as potentially postponable deaths) per 100,000 people aged 35 to 64 years as our outcome measure.
Results
The number of potentially postponable deaths from risk factor prevention and management in the population without apparent heart disease is 556.3 (plausible range, 282.3-878.1). The number of potentially postponable deaths for people with stable heart disease is 280.4 (plausible range, 90.8-521.8), 7.0 with a public-access defibrillator program (plausible range, 3.8-8.9), and 119.0 for hospitalized patients (plausible range, 15.9-297.7).
Conclusion
Although improving treatment of acute events will benefit individual patients, the potential impact on the larger population is modest. Only programs that prevent and manage risk factors can generate large declines in mortality. Significant reductions in both cardiac and noncardiac death magnify the impact of risk-factor prevention and management.
PMCID: PMC3221578  PMID: 22005632
18.  Determinants of cardiovascular disease and other non-communicable diseases in Central and Eastern Europe: Rationale and design of the HAPIEE study 
BMC Public Health  2006;6:255.
Background
Over the last five decades, a wide gap in mortality opened between western and eastern Europe; this gap increased further after the dramatic fluctuations in mortality in the former Soviet Union (FSU) in the 1990s. Recent rapid increases in mortality among lower socioeconomic groups in eastern Europe suggests that socioeconomic factors are powerful determinants of mortality in these populations but the more proximal factors linking the social conditions with health remain unclear. The HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study is a prospective cohort study designed to investigate the effect of classical and non-conventional risk factors and social and psychosocial factors on cardiovascular and other non-communicable diseases in eastern Europe and the FSU. The main hypotheses of the HAPIEE study relate to the role of alcohol, nutrition and psychosocial factors.
Methods and design
The HAPIEE study comprises four cohorts in Russia, Poland, the Czech Republic and Lithuania; each consists of a random sample of men and women aged 45–69 years old at baseline, stratified by gender and 5 year age groups, and selected from population registers. The total planned sample size is 36,500 individuals. Baseline information from the Czech Republic, Russia and Poland was collected in 2002–2005 and includes data on health, lifestyle, diet (food frequency), socioeconomic circumstances and psychosocial factors. A short examination included measurement of anthropometric parameters, blood pressure, lung function and cognitive function, and a fasting venous blood sample. Re-examination of the cohorts in 2006–2008 focuses on healthy ageing and economic well-being using face-to-face computer assisted personal interviews. Recruitment of the Lithuanian cohort is ongoing, with baseline and re-examination data being collected simultaneously. All cohorts are being followed up for mortality and non-fatal cardiovascular events.
Discussion
The HAPIEE study will provide important new insights into social, behavioural and biological factors influencing mortality and cardiovascular risk in the region.
doi:10.1186/1471-2458-6-255
PMCID: PMC1626086  PMID: 17049075
19.  Trends in suicide in a Lithuanian urban population over the period 1984–2003 
BMC Public Health  2006;6:184.
Background
Throughout the last decade of the twentieth century, Lithuania had the highest suicide rates in Europe among both men and women aged 25–64 years. The rates increased from 1986 until 1995, but later there was a slight decrease. This paper describes the trends in suicide deaths in urban population in Lithuania by gender, dates and suicide method over the period 1984–2003.
Methods
Data from the regional mortality register were used to analyze suicide deaths among all men and women aged 25–64 years in Kaunas city, Lithuania over the period 1984–2003. Age-standardized death rates per 100,000 persons (using European standard population) were calculated by gender, suicide method and dates. A joinpoint regression method was used to estimate annual percentage changes (EPACs) and to detect points where the trends changed significantly.
Results
The frequency of death by suicide among males was 48% higher in 1994–2003 than in 1984–1993. The corresponding increase among females was 28%. The most common methods of suicide among men were hanging, strangulation and suffocation (87.4% among all suicide deaths). The proportions of hanging, strangulation and suffocation in males increased by 6.9% – from 83.9% to 89.7% – compared to a 24.2% increase in deaths from handgun, rifle and shotgun firearm discharges and a 216.7% increase in deaths from poisoning with solvents, gases, pesticides and vapors. Among females, the most common methods of suicide were hanging, strangulation and suffocation (68.3% of all suicide deaths). The proportion of hanging deaths among females increased during the time period examined, whereas the proportion of poisonings with solid or liquid substances decreased.
Conclusion
Suicide rates increased significantly among urban men aged 25–64 years in Lithuania throughout the period 1984–2003, whereas among women an increasing but statistically insignificant trend was observed. There were changes in the suicide methods used by both men and women. Changes in the choice of method may have contributed to the changes in suicide rates.
doi:10.1186/1471-2458-6-184
PMCID: PMC1540427  PMID: 16836765
20.  Socioeconomic inequalities in all-cause mortality in the Czech Republic, Russia, Poland and Lithuania in the 2000s: findings from the HAPIEE Study 
Background
Relatively large socioeconomic inequalities in health and mortality have been observed in Central and Eastern Europe (CEE) and the former Soviet Union (FSU). Yet comparative data are sparse and virtually all studies include only education. The aim of this study is to quantify and compare socioeconomic inequalities in all-cause mortality during the 2000s in urban population samples from four CEE/FSU countries, by three different measures of socioeconomic position (SEP) (education, difficulty buying food and household amenities), reflecting different aspects of SEP.
Methods
Data from the prospective population-based HAPIEE (Health, Alcohol, and Psychosocial factors in Eastern Europe) study were used. The baseline survey (2002–2005) included 16 812 men and 19 180 women aged 45–69 years in Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania) and seven Czech towns. Deaths in the cohorts were identified through mortality registers. Data were analysed by direct standardisation and Cox regression, quantifying absolute and relative SEP differences.
Results
Mortality inequalities by the three SEP indicators were observed in all samples. The magnitude of inequalities varied according to gender, country and SEP measure. As expected, given the high mortality rates in Russian men, largest absolute inequalities were found among Russian men (educational slope index of inequality was 19.4 per 1000 person-years). Largest relative inequalities were observed in Czech men and Lithuanian subjects. Disadvantage by all three SEP measures remained strongly associated with increased mortality after adjusting for the other SEP indicators.
Conclusions
The results emphasise the importance of all SEP measures for understanding mortality inequalities in CEE/FSU.
doi:10.1136/jech-2013-203057
PMCID: PMC3963532  PMID: 24227051
Deprivation; Eastern Europe; Education; Inequalities; Mortality
21.  Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States 
Objective To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences.
Design Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.
Setting General population.
Participants 26 018 men and women aged 50-79 years
Main outcome measures All-cause, cardiovascular, and cancer mortality.
Results 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses.
Conclusions Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.
doi:10.1136/bmj.g3656
PMCID: PMC4061380  PMID: 24938302
22.  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
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
23.  Alcohol consumption and cognitive performance: a Mendelian randomization study 
Addiction (Abingdon, England)  2014;109(9):1462-1471.
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.
doi:10.1111/add.12568
PMCID: PMC4309480  PMID: 24716453
ADH1B; alcohol intake; cognition; memory; processing speed; verbal fluency

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