ORIGINAL STUDIES 
Aim. To evaluate the associations between main risk factors (RF) with cause-specific death in cohorts of Russian men and women.
Material and methods. Data of a number of crossectional studies conducted in different years by unified base protocol had become the subjects for the study. A total of 12,497 men and 5,039 women aged 35-74 years, residents of Moscow and S-Petersburg (former Leningrad) cities at the moment of examination, were enrolled into the study. We analyzed 17 previously selected risk factors and their associations with cause-specific mortalities: coronary heart disease (CHD), stroke, cardiovascular diseases (CVD), non-CVD, all causes. A total of 10,650 deaths were registered: 8,726 in men (for 10 years) and 1,924 – in women (for 20 years).
Results. Men died more often from all the examined causes except for stroke, what was more typical to women. Mortality in men was associated with significantly larger number of RF than in women and correlations were stronger. In particular, smoking (hazard ratio [HR] 2.25; 95% confidence interval [95%CI] 1.75-2.89; р=0.0001), high blood pressure (HR 1.78; 95%CI 1.43-2.22; р=0.0001) and history of CHD (HR 3.23; 95%CI 2.71- 3.84; р=0.0001) significantly increased CHD-related mortality in the men’s cohort but were much less significant for women. The total cholesterol level demonstrated significance in men but was not even selected in the model for women. The main RF for stroke-related mortality were smoking, high blood pressure and atrial fibrillation, while for non-cardiovascular mortality there was only one common factor – smoking. Factors associated with CVD and all-cause mortality were almost the same because CVD cover more than half in the all-cause mortality, however a larger number of predictors were reported in men.
Conclusion. The data obtained indicate: 1) considerably larger number of unfavorable risk factors in the men’s cohort, which significantly increased risk for death from any cause; 2) statistically more pronounced relation between risk factors and mortality rates in men as compared to women, especially note that mortality rates were followed up for 10 years in men and 20 years in women. It is obvious that successful prevention focused on risk factors must be gender-based.
Background. Eptifibatide achieves high local concentration via direct intracoronary (I/V) injection as it promotes clot disaggregation, but it remains unclear if it is of superior benefit than the routine intravenous (I/V) administration. Aim. The current study aimed to examine the safety and efficacy of I/C vs I/V bolus regimen dose of eptifibatide during primary percutaneous coronary intervention (PPCI).
Material and methods. Prospective, controlled, randomized study enrolled 100 patients with acute anterior ST-segment elevation myocardial infarction (STEMI) eligible for PPCI equally divided into 2 groups (group A received bolus I/C eptifibatide and group B received it I/V) followed by 12-hour continuous I/V infusion. Features related to of myocardial salvage in the form of TIMI flow grade 3, myocardial blush grade 3, ST segment resolution and left ventricular systolic function were evaluated with short-term follow up for 1 month.
Results. Mean age of the study population was 50.95±8.45years, there was statistically insignificant difference between both groups regarding baseline characteristics in age (p=0.062), gender (p=0.488), coronary artery disease risk factors (p>0.05), time from onset of pain to admission (p=0.86) or door to balloon (p=0.12). Group A achieved statistically significant better myocardial blush grade 3 (42% vs 10%, p=0.005), ejection faction 30 days after PPCI (46.11±7.81% vs 40.88±6.26%, p=0.005) but statistically insignificant TIMI flow grade 3 (p=0.29) and ST resolution (p=0.34). Incidence of complications in the hospital and 30 days after discharge was statistically insignificant (p>0.05).
Conclusion. Both regimens were safe and effective in STEMI patients undergoing PPCI and regimen of I/C bolus eptifibatide achieved better myocardial blush grade and systolic function.
The number of elderly patients with diabetes mellitus (DM) is constantly growing in general population. Accordantly, we have the growth of such patients in the group of acute coronary syndrome (ACS).
Aim. To compare clinical characteristics of the elderly patient (>75 years old) with and without DM.
Material and methods. This retrospective study included 1133 ACS patients who were aged ≥75 years and admitted to the City Clinical Hospital №1 from 01.01.2015 to 31.12.2016. Median age was 80 years, 66% were women. We analyzed 4 patient subgroups: Group 1 – 105 patients with ST-segment elevation myocardial infarction (STEMI) and DM, Group 2 – 254 STEMI patients without DM, Group 3 – 222 non-STEMI patients with DM and Group 4 – 552 non-STEMI patients without DM. We used Student’s t-test and c2 tests to find significant difference between pairs of groups.
Results. Median age of patients in 4 groups was 80, 81, 81 and 80 years (p>0.05), age variance was 75-100 years. DM was found in 29% of all elderly patients with no difference between STEMI and non-STEMI groups. STEMI and non-STEMI patients with DM were more likely women. NonSTEMI patients with DM more often had hypertension, previous stroke, lower median Hb (121 vs 127 g/l; p<0.001). Angiography data demonstrated more often three-vessel disease (43% vs 29.7%) and less one-vessel disease (15% vs 25.6%; p<0.05) between groups 3 and 4. Glomerular filtration rate (GFR) <60 ml/min/1.73 m2 occurred in 74%, 73%, 77% and 74% in patients of 4 groups (p>0,05), but GFR<45 ml/min/1.73 m2 was more prevalent in patients with DM than without DM: 45%, 39%, 45%, 36% in 4 groups. Finally, mortality rates didn’t demonstrate significant difference between DM and non-DM patients with STEMI (10% vs 13%; p>0.05) and non-STEMI (7% vs 7%) groups.
Conclusion. DM is associated with ACS approximately in one third of the elderly patients and is not associated with its type (STEMI or non-STEMI). In STEMI and non-STEMI patients the female sex and GFR level <45 ml/min/1.73 m2 were associated with DM. In non-STEMI group multi-vessel disease and presence of hypertension and previous stroke were associated with DM. We didn’t find any difference between mortality in elderly patients with and without DM.
Aim. To study the prevalence of obstructive sleep apnea (OSA) among patients with atrial fibrillation (AF) who have undergone catheter treatment for this arrhythmia, as well as to study the possible interrelationships of these sleep breathing disorders with comorbid diseases and the received therapy in this cohort.
Material and methods. 231 patients from a random sample were examined (men – 118 [51.1%], mean age 57.8±9.3 years) in the range of 1-6 months after catheter therapy for AF. All patients underwent cardiorespiratory sleep monitoring for one night. The criterion for OSA severity was apnea/hypopnea index (AHI) for hour (the norm is less than 5 events/h). Depending on the results obtained, all patients were divided into groups without apnea and with apnea of varying severity – a mild degree with an AHI value of 5 to 15 events/h, moderate severity with an AHI value of 16 to 30 events/h, and severe degree when the value of AHI more than 30 events/h. The study was performed without abolishing the basic therapy.
Results. According to the results of cardiorespiratory sleep monitoring 127 patients (56.7%) with OSA criteria, were registered. Among them, a mild degree of OSA was found in 35.4% (n=45), a moderate degree – in 40.9% (n=52), and severe one – in 23.7% (n=30) of all patients with apnea. Among patients with obstructive sleep apnea 51.1% were males. Arterial hypertension was significantly more frequent in patients with OSA of pronounced degrees of severity compared with patients without apnea (p=0.047). Weight and body mass index of patients with OSA were significantly higher than in patients without apnea (p=0.001 and p=0.001, respectively). The left atrium (LA) size in patients with severe OSA was significantly larger than in patients without apnea (p=0.0005), which may indicate a possible contribution of severe obstructive apnea to the arrhythmia generating. OSA was the strongest independent factor among others related to the LA size (odds ratio was 1.6; 95% confidence interval 1.2-2.1; p<0.0003).
Conclusion. Obstructive sleep apnea is very widespread among a cohort of patients with AF who have undergone a catheter procedure to isolate the pulmonary veins. Sleep breathing disorder is the strongest and most independent risk factor for AF associated with increased LA, among other risk factors such as age, hypertension, and obesity.
Aim. To evaluate the volume of antithrombotic therapy (ATT) at the prehospital stage in connection with the risk of thromboembolic complications, and also to study the dynamics of the frequency of administration of oral anticoagulants (ОAC) in patients with atrial fibrillation (AF) in 2015-2017.
Material and methods. The registry included 562 patients with AF at the age of 18 years and older, hospitalized in the cardiology department during 2015-2017. The registry did not include patients with AF and mechanical heart valves, mitral stenosis. The diagnosis of AF was established in accordance with the current recommendations. All patients had an assessment of the risk of thromboembolic complications on the CHA2DS2-VASc scale, the risk of bleeding on the HAS-BLED scale. The incidence of ATT at the prehospital stage was assessed depending on the risk of thromboembolic complications based on patient questioning and analysis of medical records. In addition, an assessment of the dynamics of the frequency of the OAC prescription during 2015-2017 was conducted.
Results. The overwhelming majority of patients with AF (96.1%) belonged to the group of high-risk of cardioembolic strokes according to the CHA2DS2-VASc scale and had indications for OAC therapy. The frequency of OAC prescription in patients with AF who were admitted to the cardiology department was 32% at the prehospital stage, of which 19.8% of patients took warfarin and 12.2% – direct OAC. The target level of the international normalized ratio (from 2.0 to 3.0) at the time of hospitalization was observed only in 33.6% of patients taking warfarin. Over the observation period, there was a tendency to increase the frequency of OAC prescription from 30% in 2015 to 38.4% in 2017.
Conclusion. Only 32% of patients with AF and high risk of thromboembolic complications received adequate antithrombotic therapy at the prehospital stage. According to the registry the frequency of OAC prescription in patients with AF during 2015-2017 increased by 8.4%. At the same time, there was a significant increase in the frequency of direct OAC prescription.
Aim. To study the frequency of prescribing antithrombotic agents in patients with non-valvular atrial fibrillation (AF) who were hospitalized in the cardiology department of a multidisciplinary hospital.
Material and methods. A retrospective one-time study of medical records of 765 patients with non-valvular AF treated in the cardiology department of a multidisciplinary hospital in 2012 and 2016 was performed.
Results. All patients were stratified in three groups depending on the CHA2DS2-VASc score. The frequency of prescribing antithrombotic agents was evaluated in each group. A low risk of thromboembolic complications was found in 1% (n=3) of patients in 2012 and 0.6% (n=3) in 2016. All these patients received antithrombotic agents. CHA2DS2-VASc=1 was found in 6% (n=15) of patients with AF in 2012 and in 3.4% (n=17) in 2016. A significant number of patients in this group received anticoagulant therapy with vitamin K antagonists (warfarin) or with direct oral anticoagulants. A high risk of thromboembolic complications (CHA2DS2-VASc≥2) was found in 93% of patient (n=245) in 2012 and in 96% (n=482) in 2016. Anticoagulant therapy was prescribed in 70.2% (n=172) patients with high risk in 2012 and 80% (n=387) in 2016. However, some patients with high risk of thromboembolic complications did not have the necessary therapy.
Conclusion. Positive changes in the structure and frequency of prescribing anticoagulant drugs in patients with AF and a high risk of thromboembolic complications were found during the years studied.
Different antihypertensive drugs differently affect cognitive function, and data on the effect of single-pill combination (SPC) of antihypertensive drugs on cognitive function are presented only in single studies.
Aim. To investigate the impact of amlodipine/valsartan SPC (A/V SPC) on blood pressure (BP) level and cognitive functions in the middle-aged antihypertensive treatment-naive patients with stage II grade 1-2 essential arterial hypertension.
Methods. A group of patients with stage II grade 1-2 essential arterial hypertension who had not previously received regular antihypertensive treatment (n=38, age 49.7±7.0 years) was retrospectively formed. All the patients were treated with A/V SPC and all of them achieved target office BP (less than 140/90 mm Hg). And after 12-week follow-up (since the time of reaching the target BP) the antihypertensive treatment efficacy assessment using ambulatory BP monitoring (ABPM) were performed in all included hypertensive patients. Age-matched healthy people with normal BP (n=20, mean age 45.4±5.1years) represented a control group. In all participants cognitive functions were evaluated by 5 different tests at baseline and at the end of follow-up: Montreal Cognitive Assessment (MoCA); Trail Making test (part A and part B), Stroop Color and Word Test; verbal fluency test; 10-item word list learning task. Baseline Hamilton depression and anxiety rating scale data were also available in all individuals.
Results. According to the ABPM data 24-hour, day-time and night-time systolic, diastolic and pulse BP significantly decreased after the treatment with A/V SPC (p<0.001 for systolic and diastolic BP and p<0.01 for pulse BP). After the treatment with A/V SPC significantly improved results of cognitive tests in hypertensive patients: decreased time in Trail Making Test part B (from 114.7±37.0 to 96.3±26.5 s; р=0.001); time difference between part B and part A of Trail Making Test (from 75.2±32.8 to 57.7±20.1 s; р=0.002); time in Stroop test part 3 (from 117.0±28.1 to 108.0±28.4 s; р=0.013); and interference score (from 50.9±19.2 to 43.1±22.0 s; р=0.011); increased MoCA score (from 28.4±1.3 to 29.4±1.2; р=0.001); as well as increased the 10-item word list learning task – immediate recall (from 5.7±1.3 to 6.5±1.2 words; р=0.001); 10-item word list learning task – delayed recall (from 6.3±2.1 to 6.9±1.7 words; р=0.006); literal fluency (from 11.7±3.4 to 13.2±3.2 words; р=0.020) and categorical fluency (from 7.3±2.5 to 9.5±2.9 words; p<0.001). In control group at the end of follow-up compared to baseline significantly increased the 10-item word list learning task – immediate recall (from 5.8±0.9 to 6.6±1.1 words; р<0.05) and delayed recall (from 5.9±1.8 to 8.2±1.4 words; р<0.001).
Conclusion. In retrospective analysis improvement of cognitive function was found in middle-aged patients with hypertension, taking A/V SPC for 12 weeks after reaching the target BP.
Aim. To study the significance of electrocardiography (ECG) signs for determining the hospital prognosis in patients with pulmonary embolism (PE).
Material and methods. 472 consecutive patients (49.6% men; average age 58.06±14.28 years) with PE, hospitalized to our center from 23.04.2003 to 18.09.2014 were enrolled into the study. In all cases PE was confirmed by computed tomographic pulmonary angiography and rarely by pulmonary angiography, or by pathology. Patients management was in accordance with appropriate European guidelines. Data of patients' history, clinical symptoms, biochemical markers and instrumental methods (ECG, echocardiography) were analyzed by one-dimensional logistic regression. The end points were: death, shock and hypotension, right ventricular dysfunction and pulmonary hypertension, positive cardiac biomarkers.
pulmonary embolism, electrocardiography, prognosis, collapse, hypotension, dysfunction of the right ventricle. 443 patients (93.9%) without fatal outcome were the first group and 29 patients (6.1%) with a fatal outcome – the second group. SIQIII pattern (33 vs 55.2%; p=0.015), non-complete right bundle branch block (RBBB) (16.3 vs 37.9%; p=0.001), ST segment elevation in lead III (9.7 vs 20.7%, p=0.034), atrial fibrillation (12.9 vs 37.9%, p=0.048) were observed more frequently among patients of group 2. Multivariate analysis revealed that SIQIII pattern (odds ratio [OR] 2.26; 95% confidence interval [95%CI] 1.046-4.868; p=0.038) and RBBB (OR 2.84; 95%CI 1.272-6.327; p=0.011) were associated with worse prognosis. The SIQIII pattern was significantly associated with a fatal outcome with a sensitivity of 55% and a specificity of 33% (AUC=0.611) according to ROC-analysis. Risk of hypotension was related to the following ECG-signs: the p-pulmonale (OR 1.76; 95%CI 1.001-3.088; p=0.049), negative T-wave in lead III (OR 1.8; 95%CI 1.035-3.144; p=0.037). Inversion of the T wave in lead III was associated with the development of shock (OR 1.98; 95%CI 0.891-4.430; p=0.043).
ECG-signs were also associated with the development of right ventricular dysfunction and pulmonary hypertension: right axis deviation (OR 1.035; 95%CI 1.008-1.062; p=0.01), ST-segment elevation in the AVR lead (OR 3.769; 95%CI 1.018-13.955; p=0.047), negative T wave in leads III, V1-V3 (OR 1.015; 95%CI 1.008-1.023; p=0.001 and OR 1.014; 95%CI 1.005-1.022; p=0.001, respectively), RBBB (OR 1.013; 95%CI 1.003- 1.024; p=0.012), p-pulmonale (OR 1.015; 95%CI 1.007-1.023; p=0.001), deep S in leads V5-V6 (OR 1.015; 95%CI 1.006-1.024; p=0.001). However, there was no significant relationship between ECG signs and cardiac biomarkers (troponin I and BNP).
Conclusions. SIQIII pattern, RBBB and inversion of the T wave in lead III have prognostic value in unselected population of patients with PE.
ASSOCIATED PROBLEMS OF CARDIOLOGY 
PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH 
Aim. To compare trends from CVD and cancer mortality in the Russian Federation from 2000 to 2016. depending on age and gender.
Material and methods. The official statistics on mortality of Federal state statistics Service and the data obtained in the Russian database of fertility and mortality of the Center for Demographic Studies of the Russian Economic School, Moscow (Russia) were used. Mortality from CVD, including coronary heart disease (CHD), cerebrovascular disease (CerVD), other CVD, and cancer, including prostate cancer in men and breast cancer in women, stomach cancer, trachea, bronchus and lung cancer were analyzed from 2000 to 2016.
Results. From 2000 to 2016 CVD mortality leads in comparison with deaths from cancer both in absolute number of deaths and in standardized deaths rates (SDR). There was a decrease in SDR from CVD and cancer between 2003 and 2016, however, rate of decline in the mortality rate from cancer was much less pronounced compared to CVD. At the same time, there is a trend towards a convergence in mortality from both causes in all age groups, with the exception of 75 years and older. For women in the age group of 35–64 years in 2016, the SDR from CVD was slightly lower than from cancer. The decrease in mortality from CVD was accompanied by a decrease in mortality from CHD and the CerVD, the latter was more pronounced in women. The overall mortality rate from cancer was characterized by a decrease in gastric cancer in people of both sexes, trachea, bronchus and lung cancer in men and breast cancer in women and an increase in prostate cancer in men.
Conclusion. The ratio of mortality of CVD to cancer and their age characteristics are important for health care. Keeping in mind a present high rate of CVD deaths and cancer deaths rate decline is still not enough, there are now already two big problems for the health care and prevention is a key, especially with common risk factors. These changing trends in mortality may support evidence for changes in the policy of resource allocation in the country.
Aim. To study sex and age distribution of ultrasound parameters characterizing carotid atherosclerotic (CAS) severity in the unorganized urban population.
Material and methods. The data obtained in Tomsk as a fragment of the ESSE-RF study are presented (n=1600; 25-64 years age; 59% – women). All participants signed informed consent. We studied CAS plaque count, both total and maximum plaque thickness and stenosis degree in the carotid arteries.
Results. The general population quantitative indicators of CAS increased with age, most actively in 40-54 years in men and 45-59 years in women. At the age of 40-44 years in men, the growth of the general population indicators was due to a noticeable increase in both plaque prevalence and of CAS severity. In 45-49 years, the prevalence increased intensively, whereas in 50-54 years growth of plaque count/size indicators were more attributive. In women 45-59 years old formation of the general population indicators concerned was mostly due to steady increase in the plaque prevalence, while out of all quantitative CAS parameters the total stenosis degree only increased significantly in 50-54 years. The general population indicators of CAS severity were higher in men than in women starting up with the age of 40 and until 55 the gender effect was merely explained by the difference in the plaque prevalence.
Conclusion. Features of the gender and age distribution of the quantitative parameters of CAS among the adult urban population are determined; the age periods of their most active growth are established. The presented data on the CAS severity percentile distribution can be useful as an additional tool for risk stratification and the choice of therapy/lifestyle modification tactics in people of working age. Further studies are needed to help to explain the trends and to clarify the predictive role of the indicators studied.
INNOVATIVE CARDIOLOGY 
POINT OF VIEW 
CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY 
INFORMATION 
OBITUARY 
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