The Relationship between All-Cause Natural Mortality and Copy Number of Mitochondrial DNA in a 15-Year Follow-Up Study.

We explored the relationship between the copy number of mitochondrial DNA (mtDNA-CN) and all-cause natural mortality. We examined a random population sample in 2003/2005 (n = 9360, men/women, 45-69, the HAPIEE project) and followed up for 15 years. Using a nested case-control design, we selected non-external deaths among those free from baseline cardiovascular diseases (CVD) and cancer (n = 371), and a sex- and age-stratified control (n = 785). The odds ratios (ORs) of death were 1.06 (95%CI 1.01-1.11) per one-decile decrease in mtDNA-CN independent of age, sex, metabolic factors, smoking, alcohol intake and education. The age-sex-adjusted ORs of death in the second and first tertiles of mtDNA-CN vs. the top tertile were 2.35 (95% CI 1.70-3.26) and 1.59 (1.16-2.17); an increased risk was confined to the second tertile after controlling for smoking and metabolic factors. The multivariable-adjusted OR of CVD death was 1.92 (95% CI 1.18-3.15) in tertile 2 vs. the top tertile of mtDNA-CN, and for cancer-related death the ORs were 3.66 (95% CI 2.21-6.05) and 2.29 (95% CI 1.43-3.68) in tertiles 2 and 1 vs. the top tertile. In the Siberian population cohort, the mtDNA-CN was an inverse predictor of the 15-year risk of natural mortality, due to the greatest impact of CVD and cancer-related death. The findings merit attention for exploring further the role of mtDNA in human ageing and the diversity of mortality.

Impaired lung function and mortality in Eastern Europe: results from multi-centre cohort study.

BACKGROUND: The association between impaired lung function and mortality has been well documented in the general population of Western European countries. We assessed the risk of death associated with reduced spirometry indices among people from four Central and Eastern European countries. METHODS: This prospective population-based cohort includes men and women aged 45-69 years, residents in urban settlements in Czech Republic, Poland, Russia and Lithuania, randomly selected from population registers. The baseline survey in 2002-2005 included 36,106 persons of whom 24,993 met the inclusion criteria. Cox proportional hazards models were used to estimate the hazard ratios of mortality over 11-16 years of follow-up for mild, moderate, moderate-severe and very severe lung function impairment categories. RESULTS: After adjusting for covariates, mild (hazard ratio (HR): 1.25; 95% CI 1.15‒1.37) to severe (HR: 3.35; 95% CI 2.62‒4.27) reduction in FEV1 was associated with an increased risk of death according to degree of lung impairment, compared to people with normal lung function. The association was only slightly attenuated but remained significant after exclusion of smokers and participants with previous history of respiratory diseases. The HRs varied between countries but not statistically significant; the highest excess risk among persons with more severe impairment was seen in Poland (HR: 4.28, 95% CI 2.14‒8.56) and Lithuania (HR: 4.07, 95% CI 2.21‒7.50). CONCLUSIONS: Reduced FEV1 is an independent predictor of all-cause mortality, with risk increasing with the degree of lung function impairment and some country-specific variation between the cohorts.

Traditional Eastern European diet and mortality: prospective evidence from the HAPIEE study.

PURPOSE: Cardiovascular disease (CVD) and cancer mortality rates in Eastern Europe are among the highest in the world. Although diet is an important risk factor, traditional eating habits in this region have not yet been explored. This analysis assessed the relationship between traditional dietary pattern and mortality from all-causes, CVD and cancer in Eastern European cohorts. METHODS: Data from the Health, Alcohol and Psychosocial factors in Eastern Europe prospective cohort were used, including participants from Russia, Poland and the Czech Republic. Based on food frequency questionnaire data, we constructed an Eastern European diet score (EEDS) from nine food groups which can be considered as traditional in this region. The relationship between categorical (low, moderate, high) and continuous (range 0-18) EEDS and mortality was estimated with Cox-regression. RESULTS: From 18,852 eligible participants, 2234 died during follow-up. In multivariable adjusted models, participants with high adherence to the traditional Eastern European diet had significantly higher risk of all-cause (HR 1.23; 95% CI 1.08-1.42) and CVD (1.34; 1.08-1.66) deaths compared to those with low adherence. The association with cancer mortality was only significant in Poland (high vs. low EEDS: 1.41; 1.00-1.98). From the specific EEDS components, high consumption of lard was significantly positively related to all three mortality outcomes, while preserved fruit and vegetable consumption showed consistent inverse associations. CONCLUSION: Our results suggest that traditional eating habits may contribute to the poor health status, particularly the high CVD mortality rates, of populations in Eastern Europe. Adequate public health nutritional interventions in this region are essential.

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.

Psychometric properties and confirmatory factor analysis of the CASP-19, a measure of quality of life in early old age: the HAPIEE study.

OBJECTIVES: The aim was to assess the reliability and validity of the quality of life (QoL) instrument CASP-19, and three shorter versions of CASP-12 in large population sample of older adults from the HAPIEE (Health, Alcohol, and Psychosocial factors In Eastern Europe) study. METHODS: From the Czech Republic, Russia, and Poland, 13,210 HAPIEE participants aged 50 or older completed the retirement questionnaire including CASP-19 at baseline. Three shorter 12-item versions were also derived from original 19-item instrument. Psychometric validation used confirmatory factor analysis, Cronbach's alpha, Pearson's correlation, and construct validity. RESULTS: The second-order four-factor model of CASP-19 did not provide a good fit to the data. Two-factor CASP-12v.3 including residual covariances for negative items to account for the method effect of negative items had the best fit to the data in all countries (CFI = 0.98, TLI = 0.97, RMSEA = 0.05, and WRMR = 1.65 in the Czech Republic; 0.96, 0.94, 0.07, and 2.70 in Poland; and 0.93, 0.90, 0.08, and 3.04 in Russia). Goodness-of-fit indices for the two-factor structure were substantially better than second-order models. CONCLUSIONS: This large population-based study is the first validation study of CASP scale in Central and Eastern Europe (CEE), which includes a general population sample in Russia, Poland, and the Czech Republic. The results of this study have demonstrated that the CASP-12v.3 is a valid and reliable tool for assessing QoL among adults aged 50 years or older. This version of CASP is recommended for use in future studies investigating QoL in the CEE populations.

SCORE performance in Central and Eastern Europe and former Soviet Union: MONICA and HAPIEE results.

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.

Inclusion of hazardous drinking does not improve the SCORE performance in men from Central and Eastern Europe: the findings from the HAPIEE cohorts.

BACKGROUND: The SCORE (Systematic COronary Risk Evaluation) scale uses conventional risk factors for the prediction of the 10-year risk of fatal atherosclerotic cardiovascular disease (CVD). The high-risk version of SCORE is recommended by the European Society of Cardiology for use in the populations of Central and Eastern Europe and former Soviet Union (CEE/FSU). Given the role of hazardous alcohol consumption as an important determinant of CVD mortality in CEE/FSU men, this study investigated whether adding hazardous drinking characteristics to the high-risk SCORE improves its prognostic performance in contemporary population-based male CEE/FSU cohorts. METHODS: The HAPIEE (Health, Alcohol, and Psychosocial factors In Eastern Europe) study follows Czech (seven towns), Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002-2005. In HAPIEE men (n = 8,927), 264 atherosclerotic cardiovascular deaths were registered over the median follow-up time of 6.2-8.1 years. RESULTS: In HAPIEE men, the baseline levels of the high-risk SCORE ≥5% significantly predicted fatal CVD. After controlling for the high-risk SCORE, binge drinking (drinking ≥100 g of ethanol at least once a month) and problem drinking (≥2 positive answers to CAGE questionnaire) were inconsistently associated with fatal CVD. No marked improvement in calibration and discrimination was observed for the high-risk SCORE extended by these hazardous drinking indicators, and all values of integrated discrimination improvement were <0.5%. CONCLUSIONS: Extending the high-risk SCORE by hazardous drinking parameters failed to improve its prognostic performance across male CEE/FSU population samples. Our findings tentatively support the use of the original high-risk SCORE in male CEE/FSU populations. More research is needed on the potential use of hazardous drinking in cardiovascular risk prediction.

The Profile of Glucose Lowering Therapy in Persons with Type 2 Diabetes Mellitus in an Aging Russian Population.

We aimed to analyze the profile of glucose lowering therapy (GLT) in persons with diabetes mellitus type 2 (DM2) in an aging Russian population. A random population sample (n = 3898, men/women, 55−84) was examined in Novosibirsk, during 2015−2018 (HAPIEE Project). The design of the present work is a cross-sectional study. DM2 was defined in those with a history of DM2 receiving GLT, or at a level of fasting plasma glucose (FPG) ≥7.0 mmol/L. The entire DM2 group was included in the analysis (n = 803); of these, 476 persons were taking GLT and were included in the analysis at stage 2. Regular GLT medication intake for 12 months was coded with ATC. In studied sample, the prevalence of DM2 was 20.8%. Among subjects with DM2, 59% of individuals received GLT, 32% did not. Glycemic control (FPG < 7.0 mmol/L) was achieved in every fifth participant with DM2 (35% in those receiving GLT). In frequency of GLT use, biguanides ranked in first place (75%), sulfonylurea derivatives in second (35%), insulins in third (12%), and iDPP-4 in fourth (5%). Among those receiving GLT, 24% used combined oral therapy, and 6% used insulin-combined therapy. In conclusion, in a population sample aged 55−84 examined in 2015−2018, glycemic control was achieved in every fifth participant with DM2, and in every third participant receiving GLT. The proportion of participants using new GLT drugs was small, and there was a lack of HbA1c monitoring for intensive glycemic control.

Socio-economic circumstances and food habits in Eastern, Central and Western European populations.

OBJECTIVE: To assess the relationship between several socio-economic indicators and frequency of consumption of seven predefined healthy foods (consumption of fruit, vegetables, wholegrain bread, vegetable-fat spread, vegetable cooking fat, low-fat milk and low-fat cheese) in populations from Eastern, Central and Western Europe. DESIGN: Analysis of baseline data collected in two cross-sectional cohort studies between 2000 and 2005: the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) study and the Finnish Helsinki Health Study (HHS). SETTING: Urban populations in the Czech Republic, Russia, Poland and Finland. SUBJECTS: In the HAPIEE study, random samples of men and women aged 45-69 years were drawn from population registers and electoral lists of selected cities. In the HHS, men and women aged 40-60 years employed by the City of Helsinki were recruited. Data on 21,326 working subjects from both cohorts were analysed. RESULTS: Healthy food habits were, in general, positively associated with higher education, occupational position and fewer economic difficulties, but there were differences in the strength of the gradient by food and country. Fruit consumption showed the most consistent gradients, especially in relation to socio-economic status among men (country-specific relative index of inequality (RII)=2.02-5.17) and women (RII=2.09-3.57). CONCLUSIONS: The associations between socio-economic indicators and healthy food habits showed heterogeneity between countries. Future studies of dietary behaviours should consider multiple measures of socio-economic position.

The Risk of Type 2 Diabetes Mellitus in a Russian Population Cohort According to Data from the HAPIEE Project.

The aim of this study is to investigate the 14-year risk of type 2 diabetes mellitus (T2DM) and develop a risk score for T2DM in the Siberian cohort. A random population sample (males/females, 45-69 years old) was examined at baseline in 2003-2005 (Health, Alcohol, and Psychosocial Factors in Eastern Europe (HAPIEE) project, n = 9360, Novosibirsk) and re-examined in 2006-2008 and 2015-2017. After excluding those with baseline T2DM, the final analysis included 7739 participants. The risk of incident T2DM during a 14-year follow-up was analysed using Cox regression. In age-adjusted models, male and female hazard ratios (HR) of incident T2DM were 5.02 (95% CI 3.62; 6.96) and 5.13 (95% CI 3.56; 7.37) for BMI ≥ 25 kg/m2; 4.38 (3.37; 5.69) and 4.70 (0.27; 6.75) for abdominal obesity (AO); 3.31 (2.65; 4.14) and 3.61 (3.06; 4.27) for fasting hyperglycaemia (FHG); 2.34 (1.58; 3.49) and 3.27 (2.50; 4.26) for high triglyceride (TG); 2.25 (1.74; 2.91) and 2.82 (2.27; 3.49) for hypertension (HT); and 1.57 (1.14; 2.16) and 1.69 (1.38; 2.07) for family history of diabetes mellitus (DM). In addition, secondary education, low physical activity (PA), and history of cardiovascular disease (CVD) were also significantly associated with T2DM in females. A simple T2DM risk calculator was generated based on non-laboratory parameters. A scale with the best quality included waist circumference >95 cm, HT history, and family history of T2DM (area under the curve (AUC) = 0.71). The proposed 10-year risk score of T2DM represents a simple, non-invasive, and reliable tool for identifying individuals at a high risk of future T2DM.

Dietary habits in three Central and Eastern European countries: the HAPIEE study.

BACKGROUND: The high cardiovascular mortality in Eastern Europe has often been attributed to poor diet, but individual-level data on nutrition in the region are generally not available. This paper describes the methods of dietary assessment and presents preliminary findings on food and nutrient intakes in large general population samples in Russia, Poland and the Czech Republic. METHODS: The HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study examined random samples of men and women aged 45-69 years at baseline in Novosibirsk (Russia), Krakow (Poland) and six Czech urban centres in 2002-2005. Diet was assessed using a food frequency questionnaire (at least 136 items); complete dietary information was available for 26,870 persons. RESULTS: Total energy intakes among men ranged between 8.7 MJ in the Czech sample and 11.7 MJ in the Russian sample, while among women, energy intakes ranged between 8.2 MJ in the Czech sample and 9.8 MJ in the Russian sample. A Healthy Diet Indicator (HDI), ranging from a score of 0 (lowest) to 7 (highest), was developed using the World Health Organisation's (WHO) guidelines for the prevention of chronic diseases. The mean HDI scores were low, ranging from 1.0 (SD = 0.7) among the Polish subjects to 1.7 (SD = 0.8) among the Czech females. Very few subjects met the WHO recommended intakes for complex carbohydrates, pulses or nuts; intakes of saturated fatty acids, sugar and protein were too high. Only 16% of Polish subjects met the WHO recommendation for polyunsaturated fat intake. Consumption of fruits and vegetables was lower than recommended, especially among those Russian subjects who were assessed during the low intake season. Fewer than 65% of subjects consumed adequate amounts of calcium, magnesium and potassium, when compared with the United Kingdom's Reference Nutrient Intake. CONCLUSION: This first large scale study of individual-based dietary intakes in the general population in Eastern Europe implies that intakes of saturated fat, sugar and complex carbohydrates are a cause for concern. The development of country-specific nutritional tools must be encouraged and nutritional campaigns must undergo continuing development.

Fruit and vegetable consumption and mortality in Eastern Europe: Longitudinal results from the Health, Alcohol and Psychosocial Factors in Eastern Europe study.

BACKGROUND: It is estimated that disease burden due to low fruit and vegetable consumption is higher in Central and Eastern Europe (CEE) and the former Soviet Union (FSU) than any other parts of the world. However, no large scale studies have investigated the association between fruit and vegetable (F&V) intake and mortality in these regions yet. DESIGN: The Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) study is a prospective cohort study with participants recruited from the Czech Republic, Poland and Russia. METHODS: Dietary data was collected using food frequency questionnaire. Mortality data was ascertained through linkage with death registers. Multivariable adjusted hazard ratios were calculated by Cox regression models. RESULTS: Among 19,333 disease-free participants at baseline, 1314 died over the mean follow-up of 7.1 years. After multivariable adjustment, we found statistically significant inverse association between cohort-specific quartiles of F&V intake and stroke mortality: the highest vs lowest quartile hazard ratio (HR) was 0.52 (95% confidence interval (CI): 0.28-0.98). For total mortality, significant interaction (p = 0.008) between F&V intake and smoking was found. The associations were statistically significant in smokers, with HR 0.70 (0.53-0.91, p for trend: 0.011) for total mortality, and 0.62 (0.40-0.97, p for trend: 0.037) for cardiovascular disease (CVD) mortality. The association was appeared to be mediated by blood pressure, and F&V intake explained a considerable proportion of the mortality differences between the Czech and Russian cohorts. CONCLUSIONS: Our results suggest that increasing F&V intake may reduce CVD mortality in CEE and FSU, particularly among smokers and hypertensive individuals.

Education, marital status, and total and cardiovascular mortality in Novosibirsk, Russia: a prospective cohort study.

PURPOSE: Mortality from cardiovascular diseases in Russia is among the highest in the world but little is known about its distribution by socio-demographic factors. We investigated this question in a prospective cohort study based on the Novosibirsk MONICA Project. METHOD: The cohort consisted of 6485 men and 4919 women aged 25 to 64 years at baseline, examined in 4 surveys in 1984, 1985/86, 1988/89, and 1994/95, and followed up for an average 10.3 (range 3.1-15.2) years. Participants reported their education and marital status in a questionnaire; the information on risk factors was collected in a short medical examination. RESULTS: A total of 836 male and 226 female deaths occurred during the follow up. High education was associated with reduced mortality from all causes, cardiovascular disease, and coronary heart disease in both genders. Age-adjusted relative risk of death from cardiovascular diseases for university vs. primary education was 0.6 (0.4-0.8) in men and 0.4 (0.2-0.8) in women. Adjustment for coronary risk factors and marital status substantially reduced the relative risk in men but not in women. There was no consistent relation between education and stroke. Unmarried men had higher mortality from all causes, cardiovascular and coronary heart disease than married subjects; the increased risk of divorced men was not explained by coronary risk factors or low education. Unmarried women had higher all-cause mortality than married women but associations between marital status and cardiovascular diseases were inconsistent. CONCLUSION: The educational differences in total and cardiovascular mortality in Russia are of similar direction and magnitude as in western populations. The educational differences in cardiovascular mortality in women and the increased mortality of divorced men were not explained by classical risk factors.

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.

Healthy diet indicator and mortality in Eastern European populations: prospective evidence from the HAPIEE cohort.

BACKGROUND/OBJECTIVES: Unhealthy diet has been proposed as one of the main reasons for the high mortality in Central and Eastern Europe (CEE) and the former Soviet Union (FSU) but individual-level effects of dietary habits on health in the region are sparse. We examined the associations between the healthy diet indicator (HDI) and all-cause and cause-specific mortality in three CEE/FSU populations. SUBJECTS/METHODS: Dietary intakes of foods and nutrients, assessed by food frequency questionnaire in the Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) cohort study, were used to construct the HDI, which follows the WHO 2003 dietary recommendations. Among 18 559 eligible adult participants (age range: 45-69 years) without a history of major chronic diseases at baseline, 1209 deaths occurred over a mean follow-up of 7 years. The association between HDI and mortality was estimated by Cox regression. RESULTS: After adjusting for covariates, HDI was inversely and statistically significantly associated with cardiovascular disease (CVD) and coronary heart disease (CHD) mortality, but not with other cause-specific and all-cause mortality in the pooled sample. Hazard ratios per one standard deviation (s.d.) increase in HDI score were 0.95 (95% confidence interval=0.89-1.00, P=0.068), 0.90 (0.81-0.99, P=0.030) and 0.85 (0.74-0.97, P=0.018) for all-cause, CVD and CHD mortality, respectively. Population attributable risk fractions for low HDI were 2.9% for all-cause, 14.2% for CVD and 10.7% for CHD mortality. CONCLUSIONS: These findings support the hypothesis that unhealthy diet has had a role in the high CVD mortality in Eastern Europe.

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.

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.

Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.

Melanoma diagnosis: Australian dermatologists' number needed to treat.

A retrospective audit of melanoma clinical diagnoses was undertaken for a group of 35 Australian dermatologists. This was compared with the histological diagnoses. In a 1-year period, 195 of the 686 clinically suspicious lesions were histologically confirmed as melanoma. Therefore, the number needed to treat for histological referrals for melanoma is four for this group of dermatologists. In addition, we found that the sensitivity for the diagnosis of melanoma was 89.1% if we consider all lesions that are possibly clinically suspicious of melanoma. Our results suggest that the clinical diagnosis of melanoma may not be difficult for lesions that are clinically characteristic.

Relation between heavy and binge drinking and all-cause and cardiovascular mortality in Novosibirsk, Russia: a prospective cohort study.

BACKGROUND: Moderate alcohol consumption is associated with reduced cardiovascular mortality, but binge drinking is thought to be detrimental. We examined effects of heavy and binge drinking in a population with high rates of binge drinking. METHODS: We did a prospective cohort study in Novosibirsk, Russia, in 6502 men aged 25-64 years at baseline who were examined in WHO MONICA (monitoring trends and determinants in cardiovascular disease surveys) in 1985/86, 1988/89, and 1994/95, and in a pilot study in 1984. We assessed alcohol intake and drinking pattern by questionnaire; binge drinking was defined as consumption of 160 g or greater of pure alcohol on a typical occasion. Participants were followed-up for a median of 9.5 years (range 3.1-15.2). FINDINGS: There were 836 deaths in the cohort, 395 of which resulted from cardiovascular diseases. Prevalence of binge drinking at baseline was 16% (n=1005). Adjusted relative risks for binge drinking at least once a month (compared with consumption of <80 g pure alcohol) were 1.05 (95% CI 0.80-1.36) for deaths from all causes, 0.99 (0.66-1.50) for deaths from cardiovascular disease, 1.27 (0.81-1.99) for deaths from coronary heart disease, and 2.08 (1.08-3.99) for death from external causes. Risk of total and cardiovascular mortality was raised in a small group of frequent heavy drinkers (5% [264] of all drinkers); for this group, adjusted relative risks were 1.61 (1.04-2.50) for total mortality and 2.05 (1.09-3.86) for deaths from cardiovascular disease. INTERPRETATION: The risk of death from cardiovascular disease seems to be increased in frequent heavy drinkers, but is not necessarily associated with episodic binge drinking.