Какова эффективность программ систематического популяционного скрининга для снижения бремени сердечно- сосудистых заболеваний? Резюме

Сердечно-сосудистые заболевания (ССЗ) по-прежнему являются основной причиной смерти в Европейском регионе ВОЗ. Настоящий обзор программ систематического популяционного скрининга для выявления ССЗ на доклинической стадии и факторов риска ССЗ является вторым изданием доклада, опубликованного в 2021 г. В ходе обзора был проведен новый поиск литературы и более полное исследование конкретных программ скрининга, осуществляемых на уровне отдельных стран. В новый обзор были включены итоговые результаты двух исследований, которые на момент написания предыдущего доклада были на стадии проведения. Также было выявлено 10 новых исследований, но ни одно из них не соответствовало критериям включения в обзор. Результаты обзора указывают на то, что скрининг для выявления факторов риска ССЗ не снижает заболеваемость и смертность от ССЗ и затраты в секторе здравоохранения. Скрининг для выявления ССЗ на доклинической стадии немного снижает смертность и негативные исходы, связанные с аневризмой брюшной аорты, однако эти выводы могли устареть, а снижение может быть связано с уменьшением числа курящих и улучшением лечения. Скрининг на мерцающую аритмию или на сочетание факторов риска и ССЗ на доклинической стадии незначительно влияет на заболеваемость и смертность. Наблюдаются серьезные побочные эффекты, вероятно, связанные с гипердиагностикой и избыточным лечением. Большинство исследований проводилось в западноевропейских странах. Будущие исследования можно было бы направить на изучение возможной пользы от скрининга в странах, где такие исследования еще не проводились. В немногих странах осуществляются национальные программы скрининга для выявления факторов риска ССЗ и ССЗ на доклинической стадии.

What is the effectiveness of systematic population-level screening programmes for reducing the burden of cardiovascular diseases? Summary

Cardiovascular disease (CVD) remains the main cause of death in the WHO European Region. This review of systematic screening programmes for CVD risk factors and preclinical CVD across general populations is a second edition of a report published in 2021. It includes an updated literature search and a more comprehensive investigation of country-level specific screening programmes. This updated review includes final results from two studies which were ongoing in 2021. It also identified 10 new studies, but none of these met the inclusion criteria. It shows that screening for CVD risk factors does not lower CVD morbidity and mortality or health-care expenses. Screening for preclinical CVD slightly reduces mortality and negative outcomes related to abdominal aortic aneurysm; however, the results may be outdated owing to a decline in smoking and improved treatment. Screening for atrial fibrillation or screening for a mixture of risk factors and preclinical CVD has a marginal effect on morbidity and mortality. Serious adverse effects are observed, probably due to overdiagnosis and overtreatment. Most studies were conducted in western European countries. Future research could investigate possible benefits of screening in countries that have not yet been studied. Few countries have national screening programmes for CVD risk factors and preclinical CVD.

What is the effectiveness of systematic population-level screening programmes for reducing the burden of cardiovascular diseases? Second edition

Cardiovascular disease (CVD) remains the main cause of death in the WHO European Region. This review of systematic screening programmes for CVD risk factors and preclinical CVD across general populations is a second edition of a report published in 2021. It includes an updated literature search and a more comprehensive investigation of country-level specific screening programmes. This updated review includes final results from two studies which were ongoing in 2021. It also identified 10 new studies, but none of these met the inclusion criteria. It shows that screening for CVD risk factors does not lower CVD morbidity and mortality or health-care expenses. Screening for preclinical CVD slightly reduces mortality and negative outcomes related to abdominal aortic aneurysm; however, the results may be outdated owing to a decline in smoking and improved treatment. Screening for atrial fibrillation or screening for a mixture of risk factors and preclinical CVD has a marginal effect on morbidity and mortality. Serious adverse effects are observed, probably due to overdiagnosis and overtreatment. Most studies were conducted in western European countries. Future research could investigate possible benefits of screening in countries that have not yet been studied. Few countries have national screening programmes for CVD risk factors and preclinical CVD.

Transgenerational and intergenerational effects of early childhood famine exposure in the cohort of offspring of Leningrad Siege survivors.

Famine exposure during early life development can affect disease risk in late-life period, yet, transmission of phenotypic features from famine-exposed individuals to the next generations has not been well characterized. The purpose of our case-control study was to investigate the association of parental starvation in the perinatal period and the period of early childhood with the phenotypic features observed in two generations of descendants of Leningrad siege survivors. We examined 54 children and 30 grandchildren of 58 besieged Leningrad residents who suffered from starvation in early childhood and prenatal age during the Second World War. Controls from the population-based national epidemiological ESSE-RF study (n = 175) were matched on sex, age and body mass index (BMI). Phenotypes of controls and descendants (both generations, children and grandchildren separately) were compared, taking into account multiple testing. Comparison of two generations descendants with corresponding control groups revealed significantly higher creatinine and lower glomerular filtration rate (GFR), both in meta-analysis and in independent analyses. The mean values of GFR for all groups were within the normal range (GFR less than 60 mL/min/1.73 m2 was recorded in 2 controls and no one in DLSS). Additionally, independent of the creatinine level, differences in the eating pattern were detected: insufficient fish and excessive red meat consumption were significantly more frequent in the children of the Leningrad siege survivors compared with controls. Blood pressure, blood lipids and glucose did not differ between the groups. Parental famine exposure in early childhood may contribute to a decrease in kidney filtration capacity and altered eating pattern in the offspring of famine-exposed individuals.

Case Report: Supernormal Vascular Aging in Leningrad Siege Survivors.

Age-related changes in the vascular system play an important role in the biological age and lifespan of a person and maybe affected from an early age onward. One of the indicators of changes in the vascular system is arterial wall stiffness and its main measure, i.e., carotid-femoral pulse wave velocity (cfPWV). We examined arterial wall stiffness in a sample of 305 Leningrad Siege survivors to assess how hunger and stressful conditions during fetal development and early childhood affected the state of the cardiovascular system at a later age and what factors may neutralize the negative impact sustained in early childhood. Here, we presented an evaluation of two unique patients with supernormal vascular aging (SUPERNOVA) phenotype from this cohort and described the details of congruence between hereditary resistance and practiced lifestyle yielding slower biological aging rate.

Genotype imputation and polygenic score estimation in northwestern Russian population.

Numerous studies demonstrated the lack of transferability of polygenic score (PGS) models across populations and the problem arising from unequal presentation of ancestries across genetic studies. However, even within European ancestry there are ethnic groups that are rarely presented in genetic studies. For instance, Russians, being one of the largest, diverse, and yet understudied group in Europe. In this study, we evaluated the reliability of genotype imputation for the Russian cohort by testing several commonly used imputation reference panels (e.g. HRC, 1000G, HGDP). HRC, in comparison with two other panels, showed the most accurate results based on both imputation accuracy and allele frequency concordance between masked and imputed genotypes. We built polygenic score models based on GWAS results from the UK biobank, measured the explained phenotypic variance in the Russian cohort attributed to polygenic scores for 11 phenotypes, collected in the clinic for each participant, and finally explored the role of allele frequency discordance between the UK biobank and the study cohort in the resulting PGS performance.

Physical Activity Is Associated With Sleep Quality: Results of the ESSE-RF Epidemiological Study.

BACKGROUND AND HYPOTHESIS: Physical activity (PA) is an important behavioral factor associated with the quality of life and healthy longevity. We hypothesize that extremely low and extremely high levels of daily PA (including occupational PA) may have a negative impact on sleep quality and psychological well-being. OBJECTIVE: The aim of the study is to investigate the association between the level and type of PA and sleep problems in adult population. MATERIALS AND METHODS: The sample of the study consisted of the participants from the population-based cohort of The Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study (ESSE-RF). The data of three regions (Saint Petersburg, Samara, Orenburg), varying in geographic, climatic, socioeconomic characteristics, was included into analysis. The total sample consisted of 4,800 participants (1,600 from each region; 1,926 males, 2,874 females), aged 25-64. The level of PA was evaluated using three parameters: the type of PA at work, the frequency of an intensive/high PA including sport (times a week), the mean duration of leisure-time walking (minutes a day). The measures of sleep quality were sleep duration and the frequency of difficulty falling asleep, difficulty maintaining sleep, daytime sleepiness, and sleep medication use. PA and sleep characteristics were assessed by interview carried by the trained medical staff. RESULTS: When controlling for gender, age and socioeconomic status (SES) extremely high occupational PA was a significant risk factor for difficulty falling asleep three or more times a week [OR(CI95%) = 1.9(1.2-3.0), p = 0.003] while working in a sitting position or having moderate physical load at work were not associated with sleep characteristics. Having a high physical load six or more times a week was a risk factor for difficulty falling asleep controlling for gender, age and SES [OR(CI95%) = 1.9(1.4-3.4), p = 0.001]. The association between leisure-time walking and sleep characteristics was insignificant. Walking less than an hour a day was associated with increased depression scores (46.5 vs. 41.9%, p = 0.006). CONCLUSION: High physical load at work and excessively frequent intensive PA are associated with difficulties initiating sleep and may represent a risk factor for insomnia.

Pulse wave velocity is decreased in acromegaly compared to non-acromegaly study participants with similar cardiovascular risk profile.

OBJECTIVE: Acromegaly patients were reported to have an increased arterial stiffness that could contribute to the frequent cardiovascular complications in this population. The chronic excess of GH and IGF-1 may lead to arterial stiffening via different mechanisms, including hypertension, impaired glucose tolerance and dyslipidemia, however, it is not known whether the activation of GH/IGF-1 axis might influence arterial stiffening independently of cardiovascular risk factors. The objective of this prospective case-control study was to compare arterial stiffness assessed with pulse-wave velocity (PWV) in acromegaly versus non-acromegaly group with similar cardiovascular risk profile. DESIGN: This prospective case-control study included 27 patients with active acromegaly, who underwent the assessment of clinical, physiological, biochemical parameters and the evaluation of PWV with applanation tonometry. We used "The epidemiology of cardiovascular disease in different regions of the Russian Federation" study database (n = 522) to establish a non-acromegaly control group with similar cardiovascular risk profile (n = 54). Non-acromegaly control participants underwent the same assessment as acromegaly patients except for the measurement of serum GH and IGF-1 levels. We compared PWV in acromegaly patients to the general non-acromegaly cohort and its subset, matched with acromegaly patients for cardiovascular risk factors. We also investigated the associations of PWV with clinical, physiological and biochemical parameters in acromegaly and non-acromegaly group using correlation and regression analysis with adjustment for age and sex. RESULTS: Acromegaly patients had lower PWV (6.70 (5.75-7.65) m/s) compared to unmatched non-acromegaly control cohort (7.50 (6.70-8.57) m/s, p = 0.01) and to the non-acromegaly control group matched for cardiovascular risk factors (7.45 (6.73-8.60), p < 0.01). In non-acromegaly control group PWV was associated with BMI (ρ = 0.40, p < 0.01; ß = 0.09, p < 0.01), obesity (r = 0.46, p < 0.01; ß = 1.36, p < 0.01), systolic blood pressure (ρ = 0.60, p < 0.01; ß = 0.05, p < 0.01), diastolic blood pressure (ρ = 0.62, p < 0.01; ß = 0.07, p < 0.01), triglycerides (ρ = 0.55, p < 0.01; ß = 0.58, p = 0.04), glucose (ρ = 0.54, p < 0.01; ß = 0.70, p < 0.01) and diabetes (r = 0.40, p < 0.01; ß = 1.10, p = 0.03), while in acromegaly group PWV was associated with IGF-1 expressed in mcg/ml (ρ = -0.49, p ≤0.01; ß = -0.002, p ≤0.01) and in percentage of the upper limit of the normal (ρ = -0.47, p = 0.01; ß = -0.005, p ≤0.01) as well as with diuretics treatment (ß = -1.17, p = 0.03). CONCLUSIONS: PWV is decreased in acromegaly patients compared to non-acromegaly control participants with similar cardiovascular risk profile. Future studies need to explore the role of GH/IGF-1 axis in the regulation of arterial wall properties and the reliability of PWV as a prognostic marker of cardiovascular complications in acromegaly.

What is the effectiveness of systematic population-level screening programmes for reducing the burden of cardiovascular diseases?

Cardiovascular diseases (CVDs) remain the main cause of death in the WHO European Region. This systematic literature review assesses whether systematic screening programmes for CVD risk factors and preclinical CVDs across general populations can lower the CVD burden in society. Based on several high-quality randomized controlled trials with large numbers of participants, the results clearly showed that screening for CVD risk factors has no effect on lowering CVD morbidity and mortality in society. Studies showed that screening for preclinical CVDs slightly reduces mortality and negative outcomes related to abdominal aortic aneurysm; however, these results may be outdated, as smoking has declined and treatment has improved since the studies were completed. Results on screening for atrial fibrillation and other preclinical CVDs have not yet been published. In summary, the current evidence indicates that screening for CVD risk factors does not reduce the CVD burden.

Sleep Duration, Lipid Profile and Insulin Resistance: Potential Role of Lipoprotein(a).

Lipoprotein (a) (Lp(a)) is considered a genetic factor for cardiovascular disease playing an important role in atherogenesis and thrombosis, but the evidence about its association with sleep duration is controversial. We evaluated the relation between self-reported sleep duration and Lp(a). Among 1600 participants of the population-based sample, we selected 1427 subjects without previously known cardiovascular events, who answered the questions about their sleep duration; had valid lipid profile results (total cholesterol, low- and high-density lipoproteins, Lp(a), apolipoprotein AI (ApoAI), ApoB, and ApoB/ApoAI); and did not take lipid-lowering drugs (mean age 46 ± 12 years). We performed a structured interview, which included questions about lifestyle, medical history, complaints, and sleep duration (How long have you been sleeping per night during the last month?). Sleep duration was classified as follows: <6 h/night-short, 6-9 h/night-normal, and ≥10 h/night-long. Overall, 73 respondents (5.2%) were short-sleepers and 69 (4.8%) long-sleepers. Males were slightly more prevalent among short-sleepers. The groups matched by age, body mass index, blood pressure, diabetes mellitus, and hypertension rate. Short-sleepers had lower rates of high total cholesterol (≥5.0 mmol/L), lower Lp(a) levels and lower rates of increased Lp(a) ≥0.5 g/L, and higher insulin and insulin resistance (assessed by the homeostatic model assessment for insulin resistance (HOMA-IR)). ApoAI, ApoB, their ratio, and other lab tests were similar in the groups. The multinomial logistic regression demonstrated that only the short sleep duration was independently (odds ratio (OR) 0.29, 95% confidence interval (CI) (0.09-0.91), p = 0.033) associated with Lp(a) (χ2 = 41.58, p = 0.003). Other influencing factors were smoking and HOMA-IR. Such an association was not found for long-sleepers. In conclusion, a short-sleep duration is associated with Lp(a). The latter might mediate the higher insulin resistance and higher cardiometabolic risks in short-sleepers.

Prevalence and relationship between metabolic syndrome and risk of cardiovascular disease: Evidence from two population-based studies.

BACKGROUND AND AIM: The metabolic syndrome (MetS) has become one of the most important clinical issues in the cardiovascular field for this decade because of the marked increase in cardiovascular (CV) risk associated with a clustering of risk factors. The aim of the current study was to evaluate the relationship between MetS and its components and cardiovascular disease (CVD). METHODS: This population-based cross-sectional study was based on data from two studies carried out in Russia (ESSE-RF) and Italy (PLIC). One sample from each cohort was selected, matching individuals by sex and age. A comparison between samples of MetS components distribution and CV risk, according to SCORE chart, has been conducted. RESULTS: A total of 609 individuals (mean [SD] age 55 [8] years, about 39% males) for each cohort were selected. Almost half of PLIC cohort participants belonged to the moderate CV risk group (47% vs 27%), while in ESSE-RF cohort a relatively higher prevalence of individuals classified in the high and very high risk group was observed (19% vs 11%, 21% vs 6%, respectively). Overall, 43% of ESSE-RF participants were diagnosed with MetS, compared with the 27% of PLIC members (the difference in prevalence becomes 37% vs 21%, considering a more conservative cut-off for waist circumference). Both cohorts showed a trend towards the increase of MetS components moving from the lowest to the highest CV risk class, with a high prevalence of patients with four or five MetS determinants allocated in the high/very high CV risk group. CONCLUSIONS: Developing effective public health strategies for the prevention, detection and treatment of MetS should be an urgent priority to reduce the burden of CVD, not only in subjects at high/very high CV risk, but also in those characterized by a lower risk, as even rare CV events that come from low risk group bring a tangible burden to healthcare systems.

What is the effectiveness of systematic population-level screening programmes for reducing the burden of cardiovascular disease? Summary

Cardiovascular diseases (CVDs) remain the main cause of death in the WHO European Region. This systematic literature review assesses whether systematic screening programmes for CVD risk factors and preclinical CVDs across general populations can lower the CVD burden in society. Based on several high-quality randomized controlled trials with large numbers of participants, the results clearly showed that screening for CVD risk factors has no effect on lowering CVD morbidity and mortality in society. Studies showed that screening for preclinical CVDs slightly reduces mortality and negative outcomes related to abdominal aortic aneurysm; however, these results may be outdated, as smoking has declined and treatment has improved since the studies were completed. Results on screening for atrial fibrillation and other preclinical CVDs have not yet been published. In summary, the current evidence indicates that screening for CVD risk factors does not reduce the CVD burden.

May Measurement Month 2017 in Russia: hypertension treatment and control-Europe.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative by the International Society of Hypertension aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programs worldwide. The most recent publication compared data from three surveys performed in Russian population aged 25-64 showed that the prevalence of hypertension increased by approximately 20% from 2003 to 2013. This study presents screening data collected in 2017 though the MMM17 initiative in Russia. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017 in 19 Russian cities. Blood pressure measurement, the definition of hypertension, and statistical analysis followed the standard MMM protocol. The recruitment of MMM17 participants in Russia occurred in shopping malls, colleges and universities, supermarkets, business centres, parks, and squares. Russian young cardiologists as an official section of Russian Society of Cardiology was actively involved. A total of 5660 individuals were screened. After multiple imputation, 2709 (47.9%) had hypertension. Of individuals not receiving antihypertensive medication, 753 (20.3%) were hypertensive. Of individuals receiving antihypertensive medication, 1094 (55.9%) had uncontrolled BP. Comparing with the worldwide results of MMM17 screening, Russian participants had a higher proportion of hypertension, comparable antihypertensive prescription rate, and worse hypertension control. Thus, the MMM17 project appears to be an important step in evaluating hypertension burden in Russia and emphasizes the further need to improve hypertension awareness, treatment, and control.

Overweight and Obesity in the Russian Population: Prevalence in Adults and Association with Socioeconomic Parameters and Cardiovascular Risk Factors.

OBJECTIVE: To evaluate the prevalence and geographic distribution of overweight and obesity in Russian adults aged 25-64 years as well as the association between chronic risk factors and obesity. METHODS: Data were obtained from the survey "Epidemiology of Cardiovascular Diseases and Its Risk Factors in Some Regions of the Russian Federation" (ESSE-RF). This is a large cross-sectional multicenter population-based study that included interviews and medical examination (anthropometry, blood pressure [BP] measurement, and laboratory analysis) applied in 2012-2014. RESULTS: The sample included 20,190 adults (response rate 79.4%) aged 25-64 years. Approximately one third of participants (30.3%) had obesity and another third (34.3%) were classified as overweight. BMI increased with age in both sexes. The prevalence of obesity between regions ranged from 24.4 to 35.5%. Overweight and obesity levels decreased with higher education (men only). Overall obesity rates were higher in rural than urban populations, but rates of overweight were similar in rural and urban populations. Participants with obesity were more likely to have BP > 160/100 mm Hg (odds ratio > 2.0) and also > 140/90 mm Hg, raised blood glucose, and high triglycerides. CONCLUSION: The prevalence of overweight and obesity in Russian adults aged 25-64 years is not evenly distributed geographically, but it is comparable to that of other European countries. Individuals with obesity were also more likely to have indicators of poor cardiovascular and metabolic health.

Epidemiology of cardiovascular risk factors in two population-based studies.

We aimed to compare cardiovascular risk factors prevalence in Italy and Russia through cross-sectional database analysis. The study has been based on data from ESSE-RF and from baseline of PLIC study, two population-based epidemiological studies aimed to investigate prevalence of risk factors and evaluating contribution of traditional and new risk factors into morbidity and cardiovascular mortality. A total of 2203 patients with left and right intima-media thickness (IMT) measurements constituted the source population (1205 from PLIC study and 998 from ESSE-RF study). Sample of ESSE-RF study had slightly more diabetic and hypertensive individuals, while the percentage of subjects with high cholesterol value was lower than in the other sample (67.1% vs 79.9%). The median LDL-C value was higher among individuals not treated with statins in the PLIC sample (p < 0.001), while was comparable among subjects receiving statin therapy. On the other hand, the percentage of individuals with positive cardiovascular history was higher in ESSE-RF sample. This could also explain the higher mean IMT value (0.71 ±â€¯0.17 vs 0.63 ±â€¯0.13) in the whole sample, and among patients without past cardiovascular events (regardless of statin treatment), despite some differences in major risk factors. Despite Russian and Italian populations are culturally and geographically different, they are not so different based on characteristics analyzed.

Haplotype Sharing Provides Insights into Fine-Scale Population History and Disease in Finland.

Finland provides unique opportunities to investigate population and medical genomics because of its adoption of unified national electronic health records, detailed historical and birth records, and serial population bottlenecks. We assembled a comprehensive view of recent population history (≤100 generations), the timespan during which most rare-disease-causing alleles arose, by comparing pairwise haplotype sharing from 43,254 Finns to that of 16,060 Swedes, Estonians, Russians, and Hungarians from geographically and linguistically adjacent countries with different population histories. We find much more extensive sharing in Finns, with at least one ≥ 5 cM tract on average between pairs of unrelated individuals. By coupling haplotype sharing with fine-scale birth records from more than 25,000 individuals, we find that although haplotype sharing broadly decays with geographical distance, there are pockets of excess haplotype sharing; individuals from northeast Finland typically share several-fold more of their genome in identity-by-descent segments than individuals from southwest regions. We estimate recent effective population-size changes through time across regions of Finland, and we find that there was more continuous gene flow as Finns migrated from southwest to northeast between the early- and late-settlement regions than was dichotomously described previously. Lastly, we show that haplotype sharing is locally enriched by an order of magnitude among pairs of individuals sharing rare alleles and especially among pairs sharing rare disease-causing variants. Our work provides a general framework for using haplotype sharing to reconstruct an integrative view of recent population history and gain insight into the evolutionary origins of rare variants contributing to disease.

Subclinical target organ damage in subjects with different components of metabolic syndrome.

BACKGROUND: To assess the association of metabolic syndrome (MS) and its components with target organ damage in a follow-up study of relatively healthy bank employers. METHODS: Out of 1600 random samples of office workers in Saint Petersburg (Russia), a group of 383 participants with at least one component of MS and without cardiovascular complications was selected (mean age 46.6 ± 9.0 years, 214 females (64.6%)). Follow-up visit was performed in 331 subjects. Target organ damage (TOD) was assessed by echocardiography, carotid ultrasound, applanational tonometry, brachial-ankle index, and urine albumin excretion measurements. Anthropometry, vital signs, and biochemistry were performed according to standard protocols. RESULTS: Presence of MS was not associated with higher probability of TOD. Multiple linear regression revealed significant association of all markers of TOD with older age. Hypertension was a significant predictor of left ventricular hypertrophy (LVH), increased arterial stiffness, and early signs of carotid atherosclerosis in logistic regression adjusted for age and gender. During follow-up, proportion of patients with LVH significantly decreased (from 46.7% to 32.9%, р = 0.003) and prevalence of patients with IMT > 0.09 сm increased (from 24.5% to 44.1%, p < 0.001) accompanying by significant declining of office blood pressure (BP) and total cholesterol. CONCLUSIONS: MS per se is not related to increased probability to TOD. Hypertension, female gender, and older age are main determinants of subclinical changes. After 2-years follow-up, significant LVH and renal damage regression was observed probably owing to BP reduction. Alternatively, early signs of carotid atherosclerosis increase with aging despite decreasing of the prevalence of hypercholesterolemia.

Predictors of heart rhythm disturbances in hypertensive obese patients with obstructive sleep apnea.

OBJECTIVE: To assess the incidence and predictors of heart rhythm and conduction disturbances in hypertensive obese patients with and without obstructive sleep apnea (OSA). METHODS: This is an open, cohort, prospective study. Out of 493 screened patients, we selected 279 hypertensive, obese individuals without severe concomitant diseases: 75 patients without sleep-disordered breathing (non-SDB group), and 204 patients with OSA (OSA group). At baseline, all patients underwent examination, including ECG, Holter ECG monitoring, and sleep study. During follow-up (on 3, 5, 7 and 10th years; phone calls once per 6 months), information about new events, changes in therapy and life style was collected, diagnostic procedures were performed. As the endpoints, we registered significant heart rhythm and conduction disorders as following: atrial fibrillation (AF), ventricular tachycardia, atrioventricular block (AV) 2-3 degree, sinoatrial block, significant sinus pauses (> 2000 ms), and the required pacemaker implantation. RESULTS: The median follow-up was 108 (67.5-120) months. The frequency of heart rhythm disorders was higher in OSA patients (29 cases, χ2 = 5.5; Р = 0.019) compared to the non-SDB patients (three cases; OR: 3.92, 95% CI: 1.16-13.29). AF was registered in 15 patients (n = 12 in OSA group; Р = 0.77). Heart conduction disturbance developed in 16 patients, without an association with the rate of coronary artery disease onset. Regression analysis showed that only hypertension duration was an independent predictor of AF (OR: 1.10, 95% CI: 1.04-1.16; Р = 0.001). In case of heart conduction disturbances, apnea duration was the strongest predictor (Р = 0.002). CONCLUSIONS: Hypertensive obese patients with OSA demonstrate 4-fold higher incidence of heart rhythm and conduction disturbances than subjects without SDB. Hypertension duration is an independent predictor for AF development, while sleep apnea/hypopnea duration is the main factor for heart conduction disorders onset in hypertensive obese patients with OSA.

NOTCH1 Mutations in Aortic Stenosis: Association with Osteoprotegerin/RANK/RANKL.

Background. The NOTCH pathway is known to be important in the pathogenesis of calcific aortic valve disease, possibly through regulators of osteoprotegerin (OPG), receptor activator of nuclear factor κB (RANK), and its ligand (RANKL) system. The purpose of the present study was to search for possible associations between NOTCH1 gene mutations and circulating levels of OPG and soluble RANKL (sRANKL) in patients with aortic stenosis (AS). Methods. The study was performed on 61 patients with AS including 31 with bicuspid and 30 with tricuspid aortic valves. We applied a strategy of targeted mutation screening for 10 out of 34 exons of the NOTCH1 gene by direct sequencing. Serum OPG and sRANKL levels were assessed. Results. In total, 6 genetic variants of the NOTCH1 gene including two new mutations were identified in the study group. In an age- and arterial hypertension-adjusted multivariable regression analysis, the serum OPG levels and the OPG/sRANKL ratio were correlated with NOTCH1 missense variants. All studied missense variants in NOTCH1 gene were found in Ca(2+)-binding EGF motif of the NOTCH extracellular domain bound to Delta-like 4. Conclusion. Our results suggest that the OPG/RANKL/RANK system might be directly influenced by genetic variants of NOTCH1 in aortic valve calcification.

Metabolically healthy obese and metabolically unhealthy non-obese phenotypes in a Russian population.

INTRODUCTION: The aim of the study was to estimate the prevalence of metabolically healthy obese (MHO) and metabolically unhealthy non-obese (MUNO) phenotypes in Russian population. DESIGN AND METHODS: In cross-sectional epidemiology survey "Epidemiology of cardiovascular diseases and its risk factors in some regions of the Russian Federation" a random sampling of 21,121 subjects (25-65 years), stratified by age and sex was involved. Anthropometry, blood pressure (BP) measurement and fasting blood-tests (glucose, lipids) were performed according to standard protocols. Criteria for MHO-body mass index (BMI) ≥30 kg/m2 and ≤2 of markers: HDL < 1.30 (females)/1.04 (males) mmol/l; triglycerides ≥1.7 mmol/l; glucose ≥5.6 mmol/l or treatment; waist >88 (females)/102 (males) cm and BP ≥ 130/85 mm Hg or therapy. Criteria for MUNO was BMI < 30 kg/m2 and ≥2 markers listed above. Simple tabulations, descriptive statistics, post-stratification weights and logistic regression were used for analyses. RESULTS: MHO phenotype was detected in 2856 (41.5%) obese people; MUNO phenotype-in 4762 (34.4%) non-obese subjects. Aging was negatively associated with MHO and positively with MUNO prevalence. Gender was registered as determinant only of MUNO probability. No dramatic differences in lifestyle risk factors between 3 BMI groups (lean, overweight, obese) were found out. CONCLUSION: Half of obese Russian inhabitants are metabolically healthy. At the same time, metabolic abnormalities were detected in one third of non-obese participants with a shift to male gender.