Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

Blood-Based Epigenetic Age Acceleration and Incident Colorectal Cancer Risk: Findings from a Population-Based Case-Control Study.

This study investigates the association between epigenetic age acceleration (EAA) derived from DNA methylation and the risk of incident colorectal cancer (CRC). We utilized data from a random population sample of 9,360 individuals (men and women, aged 45-69) from the HAPIEE Study who had been followed up for 16 years. A nested case-control design yielded 35 incident CRC cases and 354 matched controls. Six baseline epigenetic age (EA) measures (Horvath, Hannum, PhenoAge, Skin and Blood (SB), BLUP, and Elastic Net (EN)) were calculated along with their respective EAAs. After adjustment, the odds ratios (ORs) for CRC risk per decile increase in EAA ranged from 1.20 (95% CI: 1.04-1.39) to 1.44 (95% CI: 1.21-1.76) for the Horvath, Hannum, PhenoAge, and BLUP measures. Conversely, the SB and EN EAA measures showed borderline inverse associations with ORs of 0.86-0.87 (95% CI: 0.76-0.99). Tertile analysis reinforced a positive association between CRC risk and four EAA measures (Horvath, Hannum, PhenoAge, and BLUP) and a modest inverse relationship with EN EAA. Our findings from a prospective population-based-case-control study indicate a direct association between incident CRC and four markers of accelerated baseline epigenetic age. In contrast, two markers showed a negative association or no association. These results warrant further exploration in larger cohorts and may have implications for CRC risk assessment and prevention.

Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level: findings from the MORGAM project.

The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1-10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74-1.02), 11% (HR = 0.89; 0.84-0.95) and 5% (HR = 0.95; 0.89-1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82-1.25), 10% (HR = 1.10; 1.02-1.19) and 17% (HR = 1.17; 1.09-1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.

Hazardous alcohol consumption and problem drinking in Norwegian and Russian women and men: The Tromsø Study 2015-2016 and the Know Your Heart study 2015-2018.

AIM: Harmful use of alcohol is a worldwide public health concern. Cultural differences may affect responses to questions on alcohol problems, making international comparisons difficult. We aimed to compare self-reported alcohol consumption and problem drinking between Norwegian and Russian populations. METHODS: We used data from women and men aged 40-69 years participating in the Tromsø Study seventh survey (Tromsø7, N=17646, participation 65%), Tromsø (2015-2016), Norway, and the Know Your Heart study (KYH, N=4099, participation 51%), Arkhangelsk and Novosibirsk (2015-2018), Russia. Alcohol consumption and problem drinking were measured by the Alcohol Use Disorders Identification Test (AUDIT) via questionnaires (Tromsø7) and interviews (KYH). We compared AUDIT scores and components between populations, by sex. RESULTS: Non-drinking was more commonly reported in KYH compared with Tromsø7 (men 15.5% versus 4.9%, women 13.3% versus 7.3%). In men, hazardous consumption (41.4% versus 31.5%) and problem drinking (24.8% versus 19.6%) was higher in KYH compared with Tromsø7, but opposite for women (6.5% versus 12.0%, and 2.3% versus 5.8%). KYH men were less likely to report problem drinking behaviours than Tromsø7 men, with the exception of needing a drink first thing in the morning (13.2% versus 2.4%). KYH women consistently reported less consumption and problem drinking than Tromsø7 women. CONCLUSIONS: We found between-study differences in hazardous drinking, but in men these were lower than suggested by differences in country-level statistics on alcohol consumption and alcohol-related health-harms. Study sample selection, stronger social desirability bias effects in the Russian samples, and cultural differences in responding could have affected the results.

Influence of hypertension on systolic and diastolic left ventricular function including segmental strain and strain rate.

BACKGROUND: Left ventricular (LV) systolic and diastolic functions are important cardiovascular risk predictors in patients with hypertension. However, data on segmental, layer-specific strain, and diastolic strain rates in these patients are limited. The aim of this study was to investigate segmental two-dimensional strain rate imaging (SRI)-derived parameters to characterize LV systolic and diastolic function in hypertensive individuals compared with that in normotensive individuals. METHODS: The study sample comprised 1194 participants from the population-based Know Your Heart study in Arkhangelsk and Novosibirsk, Russia, and 1013 individuals from the Seventh Tromsø Study in Norway. The study population was divided into four subgroups: (A) healthy individuals with normal blood pressure (BP), (B) individuals on antihypertensive medication with normal BP, (C) individuals with systolic BP 140-159 mmHg and/or diastolic BP > 90 mm HG, and (D) individuals with systolic BP ≥160 mmHg. In addition to conventional echocardiographic parameters, global and segmental layer-specific strains and strain rates in early diastole and atrial contraction (SR E, SR A) were extracted. The strain and SR (S/SR) analysis included only segments without strain curve artifacts. RESULTS: With increasing BP, the systolic and diastolic global and segmental S/SR gradually decreased. SR E, a marker of impaired relaxation, showed the most distinctive differences between the groups. In normotensive controls and the three hypertension groups, all segmental parameters displayed apico-basal gradients, with the lowest S/SR in the basal septal and highest in apical segments. Only SR A did not differ between the segmental groups but increased gradually with increasing BP. End-systolic strain showed incremental epi-towards endocardial gradients, irrespective of the study group. CONCLUSION: Arterial hypertension reduces global and segmental systolic and diastolic left ventricular S/SR parameters. Impaired relaxation determined by SR E is the dominant factor of diastolic dysfunction, whereas end-diastolic compliance (by SR A) does not seem to be influenced by different degrees of hypertension. Segmental strain, SR E and SR A provide new insights into the LV cardio mechanics in hypertensive hearts.

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.

Association of Common Variants of APOE, CETP, and the 9p21.3 Chromosomal Region with the Risk of Myocardial Infarction: A Prospective Study.

The individual risk of an unfavorable cardiovascular outcome is determined by genetic factors in addition to lifestyle factors. This study was aimed at analyzing possible associations of several genetic factors with the risk of myocardial infarction (MI). For our study, we selected genes that have been significantly associated with MI in meta-analyses: the chromosomal region 9p21.3, the CETP gene, and the APOE gene. In total, 2286 randomly selected patients were included. Rs708272 and rs429358 and rs7412 were analyzed using RT-PCR via the TaqMan principle, and rs1333049 vas analyzed via a commercial KASP assay. In our sample, the frequencies of alleles and genotypes were consistent with frequencies in comparable populations of Eastern and Western Europe. Allele C of rs1333049 was significantly associated with MI among males (p = 0.027) and in the whole study sample (p = 0.008). We also revealed a significant association of the ɛ2/ɛ4 genotype of APOE with MI among males (p < 0.0001) and in the whole study sample (p < 0.0001). Thus, among the tested polymorphisms, some genotypes of rs1333049 and rs429358 and rs7412 are the most strongly associated with MI and can be recommended for inclusion into a genetic risk score.

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.

Socioeconomic inequalities in physiological risk biomarkers and the role of lifestyles among Russians aged 35-69 years.

BACKGROUND: Socioeconomic inequalities in cardiovascular (CVD) health outcomes are well documented. While Russia has one of the highest levels of CVD mortality in the world, the literature on contemporary socio-economic inequalities in biomarker CVD risk factors is sparse. This paper aims to assess the extent and the direction of SEP inequalities in established physiological CVD risk biomarkers, and to explore the role of lifestyle factors in explaining SEP inequalities in physiological CVD risk biomarkers. METHODS: We used cross-sectional data from a general population-based survey of Russians aged 35-69 years living in two cities (n = 4540, Know Your Heart study 2015-18). Logistic models were used to assess the associations between raised physiological risk biomarkers levels (blood pressure levels, cholesterol levels, triglycerides, HbA1C, and C-reactive protein) and socioeconomic position (SEP) (education and household financial constraints) adjusting for age, obesity, smoking, alcohol and health-care seeking behavior. RESULTS: High education was negatively associated with a raised risk of blood pressure (systolic and diastolic) and C-reactive protein for both men and women. High education was positively associated with total cholesterol, with higher HDL levels among women, and with low triglycerides and HbA1c levels among men. For the remaining risk biomarkers, we found little statistical support for SEP inequalities. Adjustment for lifestyle factors, and particularly BMI and waist-hip ratio, led to a reduction in the observed SEP inequalities in raised biomarkers risk levels, especially among women. High financial constraints were weakly associated with high risk biomarkers levels, except for strong evidence for an association with C-reactive protein (men). CONCLUSIONS: Notable differences in risk biomarkers inequalities were observed according to the SEP measure employed. Clear educational inequalities in raised physiological risk biomarkers levels, particularly in blood pressure and C-reactive protein were seen in Russia and are partly explained by lifestyle factors, particularly obesity among women. These findings provide evidence-based information on the need for tackling health inequalities in the Russian population, which may help to further contribute to CVD mortality decline.

Comparing prevalence of chronic kidney disease and its risk factors between population-based surveys in Russia and Norway.

BACKGROUND: Little data exists on the prevalence of chronic kidney disease (CKD) in the Russian population. We aimed to estimate the prevalence of CKD in a population-based study in Russia, compare with a similar study in Norway, and investigate whether differences in risk factors explained between-study differences in CKD. METHODS: We compared age- and sex-standardised prevalence of reduced eGFR (< 60 ml/min/1.73m2 CKD-EPI creatinine equation), albuminuria and or a composite indicator of CKD (one measure of either reduced eGFR or albuminuria) between participants aged 40-69 in the population-based Know Your Heart (KYH) study, Russia (2015-2018 N = 4607) and the seventh Tromsø Study (Tromsø7), Norway (2015-2016 N = 17,646). We assessed the contribution of established CKD risk factors (low education, diabetes, hypertension, antihypertensive use, smoking, obesity) to between-study differences using logistic regression. RESULTS: Prevalence of reduced eGFR or albuminuria was 6.5% (95% Confidence Interval (CI) 5.4, 7.7) in KYH and 4.6% (95% CI 4.0, 5.2) in Tromsø7 standardised for sex and age. Odds of both clinical outcomes were higher in KYH than Tromsø7 (reduced eGFR OR 2.06 95% CI 1.67, 2.54; albuminuria OR 1.54 95% CI 1.16, 2.03) adjusted for sex and age. Risk factor adjustment explained the observed between-study difference in albuminuria (OR 0.92 95% CI 0.68, 1.25) but only partially reduced eGFR (OR 1.42 95% CI 1.11, 1.82). The strongest explanatory factors for the between-study difference was higher use of antihypertensives (Russian sample) for reduced eGFR and mean diastolic blood pressure for albuminuria. CONCLUSIONS: We found evidence of a higher burden of CKD within the sample from the population in Arkhangelsk and Novosibirsk compared to Tromsø, partly explained by between-study population differences in established risk factors. In particular hypertension defined by medication use was an important factor associated with the higher CKD prevalence in the Russian sample.

Prevalence, awareness, treatment and control of hypertension, diabetes and hypercholesterolemia, and associated risk factors in the Czech Republic, Russia, Poland and Lithuania: a cross-sectional study.

BACKGROUND: Empirical evidence on the epidemiology of hypertension, diabetes and hypercholesterolemia is limited in many countries in Central and Eastern Europe. We aimed to estimate the prevalence, awareness, treatment and control of hypertension, diabetes and hypercholesterolemia in the Czech Republic, Russia, Poland and Lithuania, and to identify the risk factors for the three chronic conditions. METHODS: We analysed cross-sectional data from the HAPIEE study, including adults aged 45-69 years in the Czech Republic, Russia, Poland and Lithuania, collected between 2002 and 2008 (total sample N = 30,882). Among prevalent cases, we estimated awareness, treatment, and control of hypertension, diabetes and hypercholesterolemia by gender and country. Multivariate logistic regression was applied to identify associated risk factors. RESULTS: In each country among both men and women, we found high prevalence but low control of hypertension, diabetes, and hypercholesterolemia. Awareness rates of hypertension were the lowest in both men (61.40%) and women (69.21%) in the Czech Republic, while awareness rates of hypercholesterolemia were the highest in both men (46.51%) and women (51.20%) in Poland. Polish participants also had the highest rates of awareness (77.37% in men and 79.53% in women), treatment (71.99% in men and 74.87% in women) and control (30.98% in men and 38.08% in women) of diabetes. The common risk factors for the three chronic conditions were age, gender, education, obesity and alcohol consumption. CONCLUSIONS: Patterns of awareness, treatment and control rates of hypertension, diabetes and hypercholesterolemia differed by country. Efforts should be made in all four countries to control these conditions, including implementation of international guidelines in everyday practice to improve detection and effective management of these conditions.

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.

Social networks and cognitive function in older adults: findings from the HAPIEE study.

BACKGROUND: Social networks are associated with better cognitive health in older people, but the role of specific aspects of the social network remains unclear. This is especially the case in Central and Eastern Europe. This study examined associations between three aspects of the social network (network size of friends and relatives, contact frequency with friends and relatives, and social activity participation) with cognitive functions (verbal memory, learning ability, verbal fluency, processing speed, and global cognitive function) in older Czech, Polish, and Russian adults. METHODS: Linear regression estimated associations between baseline social networks and cognitive domains measured at both baseline and follow-up (mean duration of follow-up, 3.5 ± 0.7 years) in 6691 participants (mean age, 62.2 ± 6.0 years; 53.7% women) from the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) study. RESULTS: Cross-sectional analyses, adjusted for country, age, and sex, showed positive associations of global cognitive function with social activity participation and network size of friends and relatives, but not with contact frequency in either network. Further adjustment for sociodemographic, behavioural, and health characteristics attenuated the associations with network size of relatives (P-trend = 0.074) but not with network size of friends (P-trend = 0.036) or social activities (P-trend< 0.001). In prospective analyses, network size and social activity participation were also linked with better cognition in simple models, but the associations were much stronger for social activities (P-trend< 0.001) than for network size of friends (P-trend = 0.095) and relatives (P-trend = 0.425). Adjustment for baseline cognition largely explained the prospective associations with network size of friends (P-trend = 0.787) and relatives (P-trend = 0.815), but it only slightly attenuated the association with social activities (P-trend< 0.001). The prospective effect of social activities was largely explained by sociodemographic, health behavioural, and health covariates (P-trend = 0.233). Analyses of specific cognitive domains generally replicated the cross-sectional and prospective findings for global cognitive function. CONCLUSIONS: Older Central and Eastern European adults with larger social networks and greater social activities participation had better cognitive function, but these associations were stronger at baseline than over the short-term follow-up.

Long-term trends in blood pressure and hypertension in Russia: an analysis of data from 14 health surveys conducted in 1975-2017.

BACKGROUND: Hypertension is recognized as an important contributor to high cardiovascular mortality in Russia. A comprehensive analysis of data from Russian studies that measured blood pressure in population-based samples has not been previously undertaken. This study aims to identify trends and patterns in mean blood pressure and the prevalence of hypertension in Russia over the most recent 40 years. METHODS: We obtained anonymized individual records of blood pressure measurements from 14 surveys conducted in Russia in 1975-2017 relating to a total of 137,687 individuals. For comparative purposes we obtained equivalent data from 4 surveys in the USA and England for 23,864 individuals. A meta-regression on aggregated data adjusted for education was undertaken to estimate time trends in mean systolic and diastolic blood pressure, the prevalence of elevated blood pressure (> 140/90 mmHg), and hypertension (defined as elevated blood pressure and/or the use of blood pressure-lowering) medication. A meta-analysis of pooled individual-level data was used to assess male-female differences in blood pressure and hypertension. RESULTS: During the period 1975-2017 mean blood pressure, the prevalence of elevated blood pressure and hypertension remained stable among Russian men. Among Russian women, mean systolic blood pressure decreased at an annual rate of 0.25 mmHg (p < 0.1) at age 35-54 years and by 0.8 mmHg (p < 0.01) at ages 55 and over. The prevalence of elevated blood pressure also decreased by 0.8% per year (p < 0.01), but the prevalence of hypertension remained stable. Mean blood pressure and prevalence of hypertension were higher in Russia compared to the USA and England at all ages and for both sexes. CONCLUSIONS: In contrast to the generally observed downward trend in elevated blood pressure in many other countries, levels in Russia have changed little over the past 40 years, although there are some positive trends among women. Improved strategies to bring down the high levels of mean blood pressure and hypertension in Russia compared to countries such as England and the USA are important to further reduce the high burden of CVD in Russia.

Development and validation of two SCORE-based cardiovascular risk prediction models for Eastern Europe: a multicohort study.

AIMS: Cardiovascular disease (CVD) risk prediction models are used in Western European countries, but less so in Eastern European countries where rates of CVD can be two to four times higher. We recalibrated the SCORE prediction model for three Eastern European countries and evaluated the impact of adding seven behavioural and psychosocial risk factors to the model. METHODS AND RESULTS: We developed and validated models using data from the prospective HAPIEE cohort study with 14 598 participants from Russia, Poland, and the Czech Republic (derivation cohort, median follow-up 7.2 years, 338 fatal CVD cases) and Estonian Biobank data with 4632 participants (validation cohort, median follow-up 8.3 years, 91 fatal CVD cases). The first model (recalibrated SCORE) used the same risk factors as in the SCORE model. The second model (HAPIEE SCORE) added education, employment, marital status, depression, body mass index, physical inactivity, and antihypertensive use. Discrimination of the original SCORE model (C-statistic 0.78 in the derivation and 0.83 in the validation cohorts) was improved in recalibrated SCORE (0.82 and 0.85) and HAPIEE SCORE (0.84 and 0.87) models. After dichotomizing risk at the clinically meaningful threshold of 5%, and when comparing the final HAPIEE SCORE model against the original SCORE model, the net reclassification improvement was 0.07 [95% confidence interval (CI) 0.02-0.11] in the derivation cohort and 0.14 (95% CI 0.04-0.25) in the validation cohort. CONCLUSION: Our recalibrated SCORE may be more appropriate than the conventional SCORE for some Eastern European populations. The addition of seven quick, non-invasive, and cheap predictors further improved prediction accuracy.

Pharmacological management of modifiable cardiovascular risk factors (blood pressure and lipids) following diagnosis of myocardial infarction, stroke and diabetes: comparison between population-based studies in Russia and Norway.

BACKGROUND: Cardiovascular disease (CVD) mortality is substantially higher in Russia than in neighbouring Norway. We aimed to compare blood pressure- and lipid-lowering medication use and proportion meeting treatment targets between general population samples in the two countries in those with CVD and diabetes. METHODS: The study population was adults aged 40-69 years reporting a diagnosis of myocardial infarction (MI), stroke and/or diabetes participating in cross-sectional population-based studies in Russia (Know Your Heart (KYH) 2015-18 N = 626) and Norway (The Tromsø Study 2015-16 (Tromsø 7) N = 1353). Reported medications were coded according to the 2016 WHO Anatomical Therapeutic Chemical Classification system. Treatment targets were defined using the Joint European Societies guidelines for CVD prevention in clinical practice (2016). RESULTS: Age- and sex-standardized prevalence of use of lipid-lowering medications was higher in Tromsø 7 for all three conditions with a disproportionately large difference in those reporting MI (+ 48% (95% CI 39, 57%)). Proportion meeting treatment targets for LDL cholesterol was poor in both studies (age- and sex-standardized prevalence of control KYH vs Tromsø 7: MI 5.1% vs 10.1%; stroke 11.6% vs 5.8%; diabetes 24.9% vs 23.3%). Use of antihypertensive medication was higher in KYH for stroke (+ 40% (95% CI 30, 50%)) and diabetes (+ 27% (95% CI 19, 34%)) groups but approximately equal for the MI group (- 1% (95% CI -1, 1%)). Proportion meeting blood pressure targets was lower in KYH vs Tromsø 7 (MI 51.8% vs 76.3%; stroke 49.5% vs 69.6%; diabetes 51.9% vs 63.9%). CONCLUSIONS: We identified different patterns of medication use in people with CVD and diabetes. However despite higher use of lipid-lowering medication in the Norwegian study treatment to target for total cholesterol was poor in both Russian and Norwegian studies. In contrast we found higher levels of use of antihypertensive medications in the Russian study but also that less participants met treatment targets for blood pressure. Further work should investigate what factors are responsible for this seeming paradox and how management of modifiable risk factors for secondary prevention could be improved.

Uncontrolled and apparent treatment resistant hypertension: a cross-sectional study of Russian and Norwegian 40-69 year olds.

BACKGROUND: Uncontrolled hypertension is a major cardiovascular risk factor. We examined uncontrolled hypertension and differences in treatment regimens between a high-risk country, Russia, and low-risk Norway to gain better understanding of the underlying factors. METHODS: Population-based survey data on 40-69 year olds with hypertension defined as taking antihypertensives and/or having high blood pressure (140+/90+ mmHg) were obtained from Know Your Heart Study (KYH, N = 2284), Russian Federation (2015-2018) and seventh wave of The Tromsø Study (Tromsø 7, N = 5939), Norway (2015-2016). Uncontrolled hypertension was studied in the subset taking antihypertensives (KYH: N = 1584; Tromsø 7: 2792)and defined as having high blood pressure (140+/90+ mmHg). Apparent treatment resistant hypertension (aTRH) was defined as individuals with uncontrolled hypertension on 3+ OR controlled on 4+ antihypertensive classes in the same subset. RESULTS: Among all those with hypertension regardless of treatment status, control of blood pressure was achieved in 22% of men (KYH and Tromsø 7), while among women it was 33% in Tromsø 7 and 43% in KYH. When the analysis was limited to those on treatment for hypertension, the percentage uncontrolled was higher in KYH (47.8%, CI 95 44.6-50.9%) than Tromsø 7 (38.2, 36.1-40.5%). The corresponding figures for aTRH were 9.8% (8.2-11.7%) and 5.7% (4.8-6.8%). Antihypertensive monotherapies were more common than combinations and used by 58% in Tromsø 7 and 44% in KYH. In both KYH and Tromsø 7, untreated hypertension was higher in men, those with no GP visit in the past year and problem drinkers. In both studies, aTRH was associated with older age, CVD history, obesity, and diabetes. In Tromsø 7, also male gender and any drinking. In KYH, also chronic kidney disease. CONCLUSION: There is considerable scope for promoting combination therapies in line with European treatment guidelines in both study populations. The factors associated with untreated hypertension overlap with known correlates of treatment non-adherence and health check non-attendance. In contrast, aTRH was characterised by obesity and underlying comorbidities potentially complicating treatment.

Prevalence of symptoms, ever having received a diagnosis and treatment of depression and anxiety, and associations with health service use amongst the general population in two Russian cities.

BACKGROUND: Little is known about the burden of common mental disorders in Russia despite high levels of suicide and alcohol-related mortality. Here we investigated levels of symptoms, self-reports of ever having received a diagnosis and treatment of anxiety and depression in two Russian cities. METHODS: The study population was men and women aged 35-69 years old participating in cross-sectional population-based studies in the cities of Arkhangelsk and Novosibirsk (2015-18). Participants completed an interview which included the PHQ-9 and GAD-7 scales, questions on whether participants had ever received a diagnosis of depression or anxiety, and health service use in the past year. Participants also reported current medication use and medications were coded in line with the WHO anatomical therapeutic classification (ATC). Depression was defined as PHQ-9 ≥ 10 and Anxiety as GAD-7 ≥ 10. RESULTS: Age-standardised prevalence of PHQ-9 ≥ 10 was 10.7% in women and 5.4% in men (GAD-7 ≥ 10 6.2% in women; 3.0% in men). Among those with PHQ-9 ≥ 10 17% reported ever having been diagnosed with depression (equivalent finding for anxiety 29%). Only 1.5% of those with PHQ-9 ≥ 10 reported using anti-depressants and 0.6% of those with GAD-7 ≥ 10 reported using anxiolytics. No men with PHQ-9 ≥ 10 and/or GAD-7 ≥ 10 reported use of anti-depressants or anxiolytics. Use of health services increased with increasing severity of both depression and anxiety. CONCLUSION: There was a large gap between symptoms and reporting of past diagnosis and treatment of common mental disorders in two Russian cities. Interventions aimed at improving mental health literacy and reducing stigma could be of benefit in closing this substantial treatment gap.

Time trends in smoking in Russia in the light of recent tobacco control measures: synthesis of evidence from multiple sources.

BACKGROUND: The study aims at identifying long-term trends and patterns of current smoking by age, gender, and education in Russia, including the most recent period from 2008 during which tobacco control policies were implemented, and to estimate the impact on mortality of any reductions in prevalence. We present an in-depth analysis based on an unprecedentedly large array of survey data. METHODS: We examined pooled micro-data on smoking from 17 rounds of the Russian Longitudinal Monitoring Study of 1996-2016, 11 other surveys conducted in Russia in 1975-2017, and two comparator surveys from England and the USA. Standardization by age and education, regression and meta-analysis were used to estimate trends in the prevalence of current smoking by gender, age, and educational patterns. RESULTS: From the mid-1970s to the mid-2000s smoking prevalence among men was relatively stable at around 60%, after which time prevalence declined in every age and educational group. Among women, trends in smoking were more heterogeneous. Prevalence more than doubled above the age of 55 years from very low levels (< 5%). At younger ages, there were steep increases until the mid-2000s after which prevalence has declined. Trends differed by educational level, with women in the lowest educational category accounting for most of the long-term increase. We estimate that the decline in male smoking may have contributed 6.2% of the observed reduction in cardiovascular deaths among men in the period 2008-16. CONCLUSIONS: The implementation of an effective tobacco control strategy in Russia starting in 2008 coincided with a decline in smoking prevalence among men from what had been stable, high levels over many decades regardless of age and education. Among women, the declines have been more uneven, with young women showing recent downturns, while the smoking prevalence in middle age has increased, particularly among those with minimal education. Among men, these positive changes will have made a small contribution to the reduction in mortality seen in Russia since 2005.

The prospective association between frequency of contact with friends and relatives and quality of life in older adults from Central and Eastern Europe.

PURPOSE: Studies suggest that frequent contact with friends and relatives promote mental wellbeing in later life, but most evidence comes from Western populations. We investigated the prospective relationship between frequency of contact with friends and relatives and quality of life (QoL) among older Central and Eastern European (CEE) adults and whether depressive symptoms mediated the hypothesised longitudinal relationship. METHODS: Data from 6106 participants from the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) study were used. Frequency of contact with friends and relatives was measured at baseline. QoL, at baseline and follow-up, was measured by the Control, Autonomy, Self-realisation, and Pleasure (CASP) 12-item scale. After assessing the prospective association using multivariable linear regression, the mediational hypothesis was tested using path analysis. RESULTS: There was a significant prospective association between frequency of contact with friends and relatives and CASP-12 score (0-36) in fully adjusted models. Per every one unit increase in frequency of contact, there was a 0.12 (95% CI 0.06, 0.17) increase in CASP-12 score at follow-up, accounting for sociodemographic, health-related and baseline QoL. Pathway results showed that 81% of the longitudinal effect of frequency of contact on QoL was mediated through depressive symptoms. CONCLUSIONS: Frequent contact with friends and relatives improves QoL of older Central and Eastern European adults, partly through buffering against depressive symptoms. Interventions to improve QoL at older ages should incorporate effective management of common mental disorders such as depression.