Rational Pharmacotherapy in Cardiology

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Vol 15, No 5 (2019)
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612-621 708

Experimental and clinical data indicate a significant contribution of lipoprotein(a) (Lp[a]) to the atherogenesis. However, the pathophysiological mechanisms of this relationship are not fully understood.

Aim. To investigate the distribution of Lp(a) in the population of the regions participating in the Study “Epidemiology of Cardiovascular Diseases in the Regions of the Russian Federation” (ESSE-RF) and to evaluate its associations with cardiovascular risk factors.

Material and methods. Representative samples of the male and female population of 7 regions of the Russian Federation, aged from 25 to 64 years, enrolled in the multi-center cross-sectional epidemiological study were analyzed. A total of 10332 people were examined, of whom 3732 were men (36.0%) and 6600 were women (64.0%), the average age was equal in both sexes.

Results. The mean value of Lp(a) reached 22.4 mg/dl (standard deviation 21.3 mg/dl) and significantly differed from the median (11.1 mg/dl; interquartile range from 3.9 to 20.2 mg/dl), forming the right-skewed distribution in both male and female population. Lp(a) levels were statistically significantly correlated with the level of low-density lipoproteins cholesterol (LDL-C), ароВ/аpoAI and total cholesterol. Notably, the odds ratios were growing by quintiles, and increased along with increasing lipid values (p<0.0001). Lp(a) levels were also positively associated with high-sensitivity C-reactive protein (hs-CRP) and negatively correlated with blood concentration of glucose and triglycerides (TG). There were no associations with body mass index, waist circumference and smoking status.

Conclusion. According to the ESSE-RF data, there are significant positive associations of Lp(a) with the LDL-C level, the ароВ/аpoAI ratio, total cholesterol, and hs-CRP. Negative associations are established with glucose and TG levels. The future studies should be planned with the notion of the Lp(a)’s right-skewed distribution type. 

622-633 650

Aim. To evaluate gender-related differences of left atrial (LA) phasic function and structural remodeling in conjunction with the parameters of left ventricular (LV) diastolic dysfunction and central aortic pressure in patients with hypertension and recurrent atrial fibrillation (AF).

Material and methods. The comparative study included 30 men and 37 women with non-valvular AF, hypertension and LV hypertrophy. Conventional echocardiographic measures were extended with LA measures, including its volume in three phases, LAemptying fraction (LAEF), passive and active ejection fraction. The parameters of central aortic pressure were estimated by applanation tonometry method.

Results. No difference was observed between LA and LV structural parameters in men and women. However, in women LAEF (39 [28;50] vs 50 [42;55]%; p=0.02) and E/E’(9.7 [7.8;12] vs 7.1 [5.6;8.6]; p=0.001) were worse than in men. Active LA ejection fraction was higher in women (31 [21;42] vs 24 [19;31]%; p=0.04), whereas passive one – in men (12 [10;14] vs 33 [23;38]%; p<0.001), respectively. Men and women had comparable heart rate (HR), central and peripheral systolic and diastolic pressure, pulse wave velocity (PWV), but women had higher augmentation index (AI) values [33 [28;39] vs 23 [21;28]%; p<0.001], even adjusted by HR (AI 75) (34 [27;39] vs 26 [20;29]%; p<0.001). Only in men PWV weakly correlated with AI 75 (r=0.44; p=0.02 versus r=-0.11; p=0.51, respectively for men and women; intergroup differences: z=2.26; p=0.012). In a multivariate regression analysis in men LAEF was significantly associated with height, weight, E’, E/E’ and glomerular filtration rate (GFR), whereas in women – with E’ and AI 75.

Conclusion. Patients of different genders with recurrent AF and hypertension have comparable LA structuralremodeling. However, women characterized by a more pronounced decrease in LAEF and impaired LV diastolic function than men. In women as distinct from men LV filling is predominantly due to LA systole. In a multivariate regression analysis in men LAEF was significantly associated with height, weight, E’, E/E’ and GFR, whereas in women – with E’ and AI 75. 

634-640 516

Aim. To study the association of single nucleotide polymorphism rs556621 (G> T) with development of stroke in patients of the East Siberian population with cardiovascular pathology and risk factors.

Material and methods. The study involved 260 patients (157 men and 103 women) with stroke (mean age 57.0 [51.0-62.0]) and 272 patients (170 men and 102 women) of the control group (mean age 55.0 [51.0-62.0]). The examination of the main group included: collection of complaints, anamnesis, clinical examination, computed tomography of the brain, electrocardiography, echocardioscopy, ultrasound duplex scanning of extracranial brachiocephalic arteries, daily blood pressure and heart rate monitoring, analysis of the blood coagulation system. The patients of the main group have arterial hypertension, paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of the brachiocephalic arteries, disorders of the hemostatic system. The control group was studied in the framework of the HAPIEE international project. Molecular genetic research was performed by real-time polymerase chain reaction.

Results. There were no statistically significant differences in the frequencies of genotypes and single nucleotide polymorphism rs556621 alleles (G>T) in the subgroup of patients with stroke and those in the control group. The frequency of the rare TT genotype among patients with stroke was 13.3%±4.16, among healthy individuals – 8.8±3.37% (p=0.1). Gender differences when comparing the frequencies of genotypes and alleles were also not detected (p>0.05). The frequencies of the TT genotype were approximately the same in the subgroup of patients with arterial hypertension (13.1%±4.22) and in the control group (7.4±5.25%; p>0.05). No significant differences were observed in the frequencies of the rare genotype of the studied polymorphism in the subgroup of patients with supraventricular tachycardias (20.0±14.37%), hypercoagulability (15.9±7.64%) and the control group (8.8±3.37%), p>0.05. A statistically significant relationship was found between the rare genotype TT of single nucleotide polymorphism rs556621 (G>T) and the development of stroke in patients with dyslipidemia and atherosclerotic lesions of the coronary arteries (p=0.041; odds ratio 1.86, 95% confidence interval 1.02-3.41).

Conclusion. The genotype of TTs of single nucleotide polymorphism rs556621 (G> T) increases the risk of developing stroke in patients with dyslipidemia and atherosclerosis of the brachiocephalic arteries compared with carriers of the GG and GT genotypes. The obtained data are recommended to be considered when prescribing lipid-lowering and antithrombotic therapy. 

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Working Group of the NIKEA Study. Yekaterinburg: Akulina E.N., Reznik I.I.; Izhevsk: Grebnev S.A., Yezhov A., Shinkareva S.E.; Krasnodar: Kudryashov E.A., Skibitsky A.V., Skibitsky V.V., Fendrikova A.V.; Krasnoyarsk: Altayev V.D., Matyushin G.V., Nemik D.B., Pitaev R.R., Samokhvalov E.V., Stolbikov Yu.Yu.; Moscow: Balashov I.S., Voronina V.P., Gaisenok O.V., Dmitrieva N.A., Zagrebelny A.V., Zakharova A.V., Zelenova T.I., Kolganova E.V., Leonov A.S., Lerman O.V., Maximova M.A., Sladkova T.A., Shestakova G.N.; Novosibirsk: Kuimov A.D., Shurkevich A.A.; Omsk: Goodilin V.A., Loginova E.N., Nechaeva G.I.; Orel: Zhuravleva L.L., Lobanova G.N., Luneva M.M., Mitroshina T.N.; Orenburg: Kondratenko V.Yu., Libis R.A.; Rostov-on-Don: Dubishcheva N.F., Kalacheva N.M., Kolomatskaya O.E., Romadina G., Skarzhinskaya N.S., Chesnikova A.I., Chugunova I.B.; Ryazan: Dobrynina N.V., Nikolaev A.S., Trofimova Ya.M., Yakushin S.S.; Tula: Berberfish L.D., Gomova T.A., Gorina G.I., Dabizha V.G., Zubareva L.A., Nadezhkina K.N., Nikitina V.F., Renko I.E., Soin I.A., Yunusova K.N.

Background. Nicorandil is an antianginal drug for which, the ability to positively influence the prognosis of patients (pts) with stable ischemic heart disease (IHD) was confirmed in a randomized controlled trial (RCT) of IONA (the Impact Of Nicorandil in Angina). To study whether the results of RCTs are reproduced in real clinical practice seems to be an actual scientific and practical task.

Aim. To compare the data on the effectiveness and safety of nicorandil in pts with stable IHD obtained in the NIKEA observational study (OS) and in the IONA randomized study.

Material and methods. 590 pts with IHD and stable angina pectoris were included in the OS NIKEA. All pts were recommended to take nicorandil in addition to the standard antiischemic therapy. 21 months after being included in the study, 524 pts received a phone call. During the telephone contact with pts or their relatives, the life status of pts was determined. According to these results of the survey data were obtained, that 15 people died and 509 pts were alive. The events included in the primary combined endpoint (PCEP) were also determined: death from all causes, new cases of acute myocardial infarction and acute cerebrovascular accident, unscheduled operations of myocardial revascularization, hospitalization for decompensation of chronic heart failure, atrial fibrillation, unstable angina, information on taking nicorandil and other drug therapy, adverse events of drug treatment have been reported. A comparative analysis of the results of the OS NIKEA and RCT IONA was carried out. The results of the IONA study were taken according to the publication in the Lancet 2002. A comparative analysis of the results of the effectiveness of nicorandil in real practice (according to the OS results) was performed with the data obtained in the RCT: the nicorandil/placebo groups in the RCT were compared with the adherent/non-adherent nicorandil groups in the OS.

Results. The follow-up duration in both studies was similar and averaged 1.6±0.5 years at RCT IONA and 1.8±0.4 years at NIKEA study. The average age of pts was 67,0±8,0 years in RCT and 65.1±9.6 years in OS. In pts of OS more pronounced comorbidity was noted (cardiovascular diseases, diabetes mellitus). Drugs that favorably affect the prognosis in pts with IHD were more often prescribed to NIKEA study pts (p<0.05). In both RCTs and OS, the antianginal effectiveness of nicorandil was confirmed. According to the OS results, a reduction in the number of angina attacks and a decrease in the need for short-acting nitrates were demonstrated. The frequency of PCEP components was higher in RCT.

Conclusion. Long-term outcomes according to the NIKEA observational program for various components of the PCEP turned out to be similar to the results of RCT IONA. It is demonstrated the efficacy of nicorandil in real clinical practice. 

649-655 577

Aim. To conduct a comparative analysis of the significance of the influence of various factors and their combinations on the survival of patients with atrial fibrillation (AF) in the REKUR-AF study.

Material and methods. The database includes 896 patients with AF over 18 years old who applied to medical organizations in the city of Kursk and seven districts of the Kursk region from September 2015 to August 2016. Achievement by the patients of the “end point” (death from any cause) was assessed using a telephone contact for a period of 9.0±0.55 months from the end of the database formation. Data were obtained on 532 patients, of which 60 patients reached the end point. To study the differences in survival in subgroups of patients with different characteristics, two groups of categorized factors were analyzed – clinical (sex, age, form of AF, etc.) and pharmacological (use of different classes of drugs). The necessary information was obtained from outpatient cards analyzed when patients were included in the study.

Results. The survival rate of patients with AF was significantly (p<0.05-0.001) influenced by the following factors and their categories: age (<60 years – 92.5%, 60-65 years – 92.9%, over 75 years – 80.1%); AF form (paroxysmal – 95.1%, persistent – 93.2%, permanent – 84.4%); stable angina (SA) (presence – 86.5%, absence – 90.7%); chronic heart failure functional class (CHF FC) (I-II – 95.9%, III – 91.5%, IV – 69.6%); glomerular filtration rate (GFR) (>50 ml/min – 89.6%, 30-50 ml/min – 85.8%, <30 ml/min – 72.7%); diabetes mellitus (DM) (presence – 81.9%, absence – 90.4%), hospitalization for the year preceding inclusion in the study (presence – 85.5%, absence – 97.3%), the use of oral anticoagulants (OAC) (presence – 96.7%, absence – 87.1%). In subgroups of patients with the above mentioned categories (especially the most severe) of the studied factors, significant (p<0.05-0.01) differences in the proportion of surviving patients depending on the appointment of OAC were revealed: age >75 years – 78.2% and 100%; permanent form of AF – 81.9% and 96.1%, the presence of SA – 85.0% and 94.7%; CHF FC IV – 67.0% and 91.7%; GFR<30 ml/min – 62.5% and 100%; presence of DM – 80.7% and 88.2%.%; the presence of hospitalizations in the last year – 82.9% and 97.2%; >5 points on the CHA2DS2VASc scale – 67.0% and 91.7%, heart rate >90/min – 68.8% and 100% of patients with the absence and presence of the OAC therapy, respectively. Cox regression analy sis revealed clinical predictors contributing to an increase in the risk of death: age over 75 years, permanent form of AF, CHF FC III-IV, the presence of DM, the presence of previous hospitalizations. The absence of the OAC taking was accompanied by an increase in the risk of death by 3.66 times.

Conclusion. The results of the REKUR-AF study allowed to establish the most significant factors affecting the survival of patients with AF: age, form of AF, CHF FC, presence of DM, hospitalization in the last year preceding the inclusion of patients in the study, OAK taking. The prescription of OAC is a priority predictor that improves survival in patients with AF. 

656-662 658

Aim. To assess the demographic and clinical characteristics, drug treatment and outcomes in patients with a history of acute cerebrovascular accident (ACVA) and with concomitant history of myocardial infarction (MI) in clinical practice based on outpatient and hospital parts of REGION registry.

Material and methods. The total 1886 patients with a history of ACVA (aged of 70.6±12.5 years, 41.9% men) were enrolled into the outpatient registry REGION (Ryazan) and the hospital registry REGION (Moscow). 356 patients had ACVA and a history of MI (group “ACVA+MI” and 1530 patients had ACVA without history of MI (group “ACVA without MI”). The incidence of cardiovascular diseases (CVD), non-CVD comorbidities, drug therapy and outcomes were analyzed.

Results. In the group ACVA+MI compared with group ACVA without MI the significantly higher proportions of patients with the following conditions (diagnosis) were revealed: arterial hypertension (AH) – 99.1% and 94.2%; coronary heart disease (CHD) – 100% and 57%; chronic heart failure (CHF) – 61.5% and 41.8%; atrial fibrillation (AF) – 42.7% and 23.8%; repeated ACVA – 32.9% and 18.9%, respectively, p<0.0001 for all. In ACVA+MI and ACVA without MI groups the respective proportions of patients were smokers – 16.2% and 23.7% (p=0.10), had a family history of premature CVD – 3.2% and 1.2% (p=0.01), and had a hypercholesterolemia – 47% and 59.7% (p<0.001). The incidence of drug administration with proved positive prognostic effect was insufficient in both groups, but higher in the ACVA+MI group compared with ACVA without MI group (on average 47.1% and 40%, respectively), including: anticoagulants in AF – 19.1% and 21.4% (p=0.55); antiplatelets in CHD without AF – 69.4% and 42% (p<0.001); statins in CHD – 26.4% and 17.2% (p<0.001); beta-blockers in CHF – 39% and 23.8% (p=0.002), respectively. During 4- year follow-up in the group ACVA+MI compared with group ACVA without MI there were significantly higher all-cause mortality – 44.9% and 26.8% (p<0.001), nonfatal recurrent ACVA – 13.7% and 5.6% (p=0.0001), and nonfatal MI – 6.9% and 1.0% (p<0.0001), respectively.

Conclusion. The proportion of patients with a history of MI was 18.9% among the patients with a history of ACVA. In patients of ACVA+MI group, compared with patients of ACVA without MI group a higher incidence of the following characteristics was revealed: a presence of AH, CHD, CHF, AF, repeated ACVA and a family history of premature CVD. The incidence of taking drug with proved positive effect on prognosis in patients of the compared groups was insufficient, especially of statins and anticoagulants in AF. During the follow-up period ACVA+MI group was characterized by a higher all-cause mortality and higher incidence of nonfatal ACVA and MI. In these patients the improvement of the quality of pharmacotherapy and of the secondary prevention effectiveness are the measures of especial importance. 


663-669 631

Aim. To evaluate the therapeutic efficacy of a combination of ivabradine and beta-blockers (BAB) in patients with stable angina, initially taking only BAB and not reaching the target heart rate (HR) due to the risk of hypotension.

Material and methods. A prospective observational post-registration study was performed at the Research Institute for Complex Issues of Cardiovascular Diseases. The study included 50 patients with stable angina pectoris (diagnosed by coronary angiography in combination with clinical manifestations of angina of functional class II-III according to the Canadian classification) and an initial sinus rhythm with a heart rate of more than 70 beats per minute. These patients have already taken BAB. Heart rate, the number of angina attacks, nitrate intake and quality of life indicators according to the questionnaire were evaluated as criteria for therapeutic efficacy.

Results. Taking the study drug in combination with BAB led to a significant decrease the average heart rate at rest by 20%, as well as after a six-minute walk test (TLC) in most patients (p<0.050), and a decrease in the total number of angina attacks per week from 5 to less than 1 (p<0.050) and the frequency of nitrate intake for the relief of angina attacks from 58% to 20% (p=0.001). Therapy with ivabradine (Bravadin) was well tolerated by patients: there were no adverse events in the observed sample of patients, patients had a high adherence to treatment (100% of the contents of handed out blisters were used). During the 3 months of follow-up, according to the EQ-5D-5L quality of life questionnaire, patients improved their perception of their own health level (p<0.050), the number of patients experiencing mild (p=0.034) and strong (p=0.041) mobility limitations decreased; strong (p=0.024) restriction in self-care, mild (p=0.041) and strong (p=0.024) restriction of daily activities, mild manifestation of pain (p=0.009) and mild anxiety (p=0.027) also were reduced compared with the initial questionnaires.

Conclusion. Ivabradine (Bravadin) in addition to BAB is an effective and safe antianginal therapy for the prevention of angina attacks by reducing the initially high heart rate in patients with angina pectoris of functional class II-III.

670-674 469
Warfarin-induced skin necrosis (WISN) is a rare complication of antivitamin K therapy, which occurs in 0.01-0.1% of cases and develops during the first 10 days of the therapy start in the fat-rich tissues. In the literature, there is the increasing number of descriptions of case reports of the so-called atypical WISN, which develops much later – in months and even years from the therapy start – on the other parts of the body, mainly on the extremities. Conceivably there are several risk factors for the WISN development: a noncompliance of the antivitamin K regiment intake or the repeated therapy, a liver dysfunction or drug interactions, but a clear relationship has not been established yet as there have been only several hundred cases of WISN registered worldwide. One of the risk factors for WISN is congenital thrombophilia. The case presented demonstrates the development of an atypical WISN, which developed after 2 months from the start of the treatment with warfarin in a patient who is a carrier of mutation factor V Leiden. A resolution of the symptoms occurred as a result of treatment with unfractioned heparin.
675-680 487

Direct oral anticoagulants (not vitamin K antagonists), unlike standard oral anticoagulants (e.g. warfarin), have a predictable manifestation of the anticoagulant effect and the possibility of using a fixed dose without the need for constant monitoring of the anticoagulant effect. The rapid onset and cessation of the effect of direct oral anticoagulants, the relatively low likelihood of interaction with food and other drugs compared to warfarin, have expanded the possibilities of anticoagulant therapy.

Direct oral anticoagulants, particularly rivaroxaban, are widely used for deep vein thrombosis/pulmonary embolism prevention and treatment, and for stroke prevention in patients with atrial fibrillation. Awareness of side effects is mostly associated with bleeding risks while other problems with the use of this medication attract less physicians’ attention. These side effects mainly include liver damage and some other rare side effects. This article describes a clinical case of rivaroxaban-associated drug-induced liver injury in patient with first diagnosed atrial fibrillation and normal baseline liver enzymes. A literature review focused on this problem is also presented. 


681-689 348

Aim. To assess the cost and importance of the vital and essential medicines for the treatment of 12 groups of internal diseases purchased in 2017 by the «key» medical organizations in the subjects of Russian Federation with the funding from the system of compulsory medical insurance.

Material and methods. We conducted the ABC and VEN analysis of the medications (according to the list of vital and essential medicines and clinical guidelines) treatment of 12 groups of internal diseases purchased in 2017 by the «key» medical organizations in the subjects of Russian Federation.

Results. The study revealed that medical organizations show insufficient level of registration (less than 10% of the key medical organizations) regarding the medicines prescribed in the groups of diseases according to ICD-10, which complicates conducting large-scale research aimed at assessing the clinical and economical relevance of the provided treatment. Despite the fact that during the process of purchasing by medical organizations they are guided by the list of vital and essential medicines, the percent of expenses for the medicines which are not in the list, is still very high (more than 20%). At the same time in most of the groups being assessed, in the most expensive group A (80% of expenses) there were the medications not included in the list of vital and essential medicines. 

Conclusion. Assessment of correspondence between the medicines purchased by the medical organizations and those recommended by the guidelines is complicated due to the absence of clinical guidelines for the wide range of internal diseases. According to the preliminary assessments, the wide range of medications mentioned in clinical guidelines compared to the list of vital and essential medicines significantly broaden the number of essential medicines from the point of VEN-analysis. 

690-696 466

Aim. To compare the results of 3-year follow-up of patients with peripheral atherosclerosis (PA) in two patient cohorts: during outpatient monitoring by cardiologists and when observed by surgeons.

Material and methods. The first group included 131 patients with PA who sought medical attention in outpatient clinic in 2013-2014 and then were observed by a surgeon. The second group is represented by 454 patients with PA who sought medical attention in outpatient clinic in 2010- 2012 and then underwent observation by a cardiologist as a part of a pilot project. The average follow-up duration in the studied groups was three years. The groups were compared according to the main demographic, anthropometric indicators, the presence of risk factors for atherosclerosis, comorbidity, the prevalence of atherothrombotic events in history, laboratory and instrumental examination data. Additionally, after 3 years of observation the incidence of deaths and amputations was assessed in groups.

Results. Patients of the second group were older than these in the first group (p<0.001). Patients of the group 1 compared to the group 2 were more often overweight (p=0.005), suffered from diabetes mellitus (p<0.001), had a disability (p<0.001). Among patients of the group 2 compared with the group 1, the clinical picture of angina pectoris (p=0.001), rhythm disorders (p=0.058) were more often observed, they had a greater number of myocardial infarctions (p<0.001) and myocardial revascularization operations in the history: coronary bypass surgery (p=0.029), percutaneous coronary interventions (p<0.001), and underwent coronary angiography (p<0.001). Patients in group 2 were more likely to receive statins (p<0.001), β-blockers (p<0.001), angiotensin-converting enzyme inhibitors, and calcium channel blockers, angiotensin II receptor blockers, and antiarrhythmics (p<0.001). Pentoxifylline was prescribed more often in the first group (p<0.001). With a three-year observation of PA patients a fatal outcome occurred in 8.2% of cases, amputation – in 1.4%. In the first group, compared with the second one, there were more often observed deaths in general (p=0.023), death from cardiac causes, stroke, disability (p=0.005) and amputations (p=0.003). The risk of adverse outcomes (death and amputations) was increased in the presence of signs of chronic lower limb ischemia of stage III, a history of amputation, more than 70% stenosis and occlusions of lower limb arteries, chronic lung disease, and angina symptoms. The risk of adverse outcomes was decreased in outpatient observation by cardiologist, taking statins, aspirin, and performing exercise therapy.

Conclusion. Observation of PA patients by a cardiologist results in more frequent optimal drug therapy (due to the better adherence of cardiologists to clinical recommendations for the treatment of such patients) and improves the prognosis of these patients. 

697-705 392

Background. According to the literature data, acute coronary syndrome (ACS) in 2-20 % of cases is combined with atrial fibrillation (AF). According to the current guidelines of the European Society of Cardiology (ESC), patients with coexisting AF and ACS should receive dual antiplatelet therapy for the prevention of recurrent cardiovascular events and anticoagulant therapy for the prevention of thromboembolic complications. However, this combination is fraught with the development of hemorrhagic syndrome.

Aim. To develop a model and software module for predicting possible bleeding in patients with ACS combined with AF taking three-component antithrombotic therapy.

Materials and Methods. To build prognostic models for the development of hemorrhagic syndrome, a statistical method was used for classification trees and the neural network procedure implemented in the STATISTICA package. To build prognostic models, a sample was used consisting of 201 patients with a combination of ACS and AF with and without fatal outcome, the state of which was described by 42 quantitative and qualitative clinical indicators. The control group included 205 patients with ACS and intact sinus rhythm.

Results. To identify predictors of predictive models of the possible development of hemorrhagic syndrome in patients with triple antithrombotic therapy, the Spearman correlation coefficient was used. The study of correlations allowed to reveal clinical indicators – predictors of prognostic models. After analyzing the predictive ability of the developed models, a software module was created in the Microsoft Visual C # 2015 programming environment that allows determining the possibility of hemorrhagic syndrome in patients with a combination of ACS and AF using classification trees and neural networks.

Сonclusion. A classification model and a software module were developed to predict possible bleeding in patients taking three-component antithrombotic therapy. Models contain both quantitative and qualitative (categorical) clinical indicators. The current level of development of data analysis technologies opens up broad horizons for medicine in solving problems on real medical data, without translating them into scoring risk scales, including prediction of the diagnosis of the disease, stage of the disease, treatment outcome, possible complications, etc. High reliability of such systems can be provided by large volumes of medical data accumulated on servers. 


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Aim. To assess the impact of arterial hypertension (AH) on the long-term outcomes in patients after acute myocardial infarction (AMI).

Material and methods. 160 patients were included: 106 (66.2%) men and 54 (33.8%) women, average age 74.2±11.2 years, discharged from Moscow hospitals with a diagnosis of AMI (from March 01, 2014 till June 30, 2015) and applied to the city polyclinic №9 in Moscow or its branches for outpatient observation. The information was obtained on the basis of medical documentation of the polyclinic and data of patients’ examination/questioning by phone, conducted every 2 months. The follow-up duration was 1 year, the incidence of cardiovascular complications (CVC) was estimated: death, nonfatal AMI, nonfatal cerebral stroke, new cases of atrial fibrillation (AF), hospitalization for unstable angina, hypertensive crisis, heart failure, unplanned surgical interventions on the heart and blood vessels.

Results. AH before the development of reference AMI was observed in 118 (73.4%) patients: 48 women and 70 men; in women, AH was recorded more often than in men: 88.9% and 66.0%, respectively, p<0.05. Patients with AH were older than patients without AH: 63.0 (54.0; 74.0) and 55.5 (49.0; 61.0) years, respectively, p<0.001, among them there were more retirees 76 (64.4%) and patients with disabilities 45 (38.1%), p<0.05. Patients with AH compared with patients without AH were less likely to smoke (18.6% and 38.1%, respectively) and drank alcohol (30.5% and 52.4%, respectively), p<0.05 for both; more likely to visit the outpatient clinic (89.0% and 66.7%, respectively), p<0.05. There were no significant differences between the groups of patients with and without AH in the history of cerebral stroke, AMI, arrhythmia by AF type, diabetes mellitus and obesity, except for angina of tension (18.6% and 2.4%, respectively) and hypercholesterolemia (37.3% and 11.9%, respectively), p<0.05 for both. Despite the fact that patients with AH were significantly more often prescribed antihypertensive, lipid-lowering and antithrombotic drugs before reference AMI, the frequency of their use was low: renin-angiotensin-aldosterone system blockers were prescribed in 70 (59.3%) patients, beta-blockers – in 35 (29.7%), calcium antagonists – in 20 (16.9%), diuretics – in 13(11.0%), antiplatelet agents – in 39 (33.1%), statins – in 9 (7.6%) patients. After one year of follow-up, CVC was registered in 33 (28.0%) patients with AH and 9 (21.4%) patients without AH (p=0.41). There was no statistically significant effect of AH on long-term outcomes of AMI, adjusted risk ratio =1.30 [95% confidence interval 0.68- 2.49], p>0.05. The effect of AH on the development of CVC, estimated using the Kaplan-Mayer curve, was not statistically significant (p=0.120).

Conclusion. During 1 year of follow-up after AMI in patients with AH the frequency of CVC – death, nonfatal AMI, nonfatal cerebral stroke, new cases of AF, hospitalization for unstable angina, hypertensive crisis, heart failure – did not exceed the overall frequency of CVC in patients without AH.


713-724 768
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias in clinical practice and important additional risk factor for the development of cognitive impairment (CI) and dementia as it has been shown in recent studies. According to the Diagnostic and statistical manual of mental disorders latest revision CI refers to a decrease of one or more higher cortical functions that provide the processes of perception, storage, transformation and transmission of information compared to the premorbid level. The main hypothesis that explains the relationship between AF and dementia is the assumption that in the presence of this arrhythmia a brain substance is damaged due to microembolism and cerebral microbleeding. The high clinical significance of AF as well as CI served as a background for the development by European experts several consensus documents concerning the problem of the relationships between these conditions. In addition, they emphasize the role of anticoagulant therapy as a preventing tool for the development of stroke, which can be a factor in the CI progression in patients with AF, with particular priority to direct oral anticoagulants (DOACs). In randomized clinical trials, meta-analyses and systematic reviews have been shown that the use of DOACs, as compared to vitamin K antagonists, is a more rational strategy for preventing stroke associated with AF. Among the DOAC class, rivaroxaban is worth noticing as a drug that has a favorable efficacy profile for primary and secondary stroke prevention. Rivaroxaban distinguishing characteristics are a once daily administration as well as a calendar package which is practically important for patients with CI.
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The article is devoted to the influence of magnesium on the homeostasis of the body and, in particular, on the cardiovascular system. It describes the importance of the presence and effects of magnesium on various key processes and functions occurring in the body. The reasons for the lack of magnesium and ways to replenish it both in the natural way (eating, certain foods) and magnesium preparations are considered. The article provides examples of large randomized studies that prove the importance of the influence of normal magnesium levels on human health in general and on the state of the cardiovascular system. These studies show how magnesium deficiency increases the risk of cardiovascular diseases and how it can be reduced. It is also shown which trace elements and vitamins are closely related to magnesium metabolism, and how they (in particular, potassium and vitamin B6) improve and facilitate the normalization of magnesium levels. It is noted how comorbidity decreases with the normalization of magnesium level – the higher the magnesium level in the blood plasma (closer to the upper limit and more), the less comorbidity and longer life expectancy. Magnesium is an absolutely essential ion and a good medicine. Magnesium deficiency and hypomagnesemia are quite common, difficult to diagnose (due to underestimation and rare level control) and accompany many diseases of the cardiovascular system and beyond. The widespread use of organic magnesium salts would improve the situation as a whole, due to their universal multiple effect on many processes in the body. This is an integral part of therapeutic and preventive measures in patients with already existing diseases and in people who do not have diseases, but who are at risk due to existing hypomagnesemia.
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Despite the current possibilities of using different classes of antihypertensive drugs that effectively reduce blood pressure and significantly improve the long-term prognosis of patients, the problem of uncontrolled arterial hypertension has not lost its importance and its solution in a particular clinical situation often remains very difficult. The term "uncontrolled arterial hypertension" can be used in all cases where arterial pressure has not been achieved. The true prevalence of uncontrolled arterial hypertension has not been established, and its study is hampered primarily by the fact that not all patients initially receive antihypertensive therapy that meets generally accepted standards. Currently, the tactics of management of patients with uncontrolled hypertension involves the use of combinations of antihypertensive drugs. Rational combinations, according to the new recommendations for the diagnosis and treatment of arterial hypertension in 2018, remain a combination of blockers of the renin-angiotensin-aldosterone system – angiotensin-converting enzyme inhibitors or receptor blockers to angiotensin with a calcium antagonist or diuretic, preferably in one tablet. With the ineffectiveness of dual therapy needs to be assigned to a third antihypertensive drug. Among the most modern antihypertensive drugs can be considered a triple fixed combination of lisinopril, amlodipine and indapamide. All the components included in the composition of the drug, has proved its high efficiency and safety. Uncontrolled arterial hypertension remains one of the most urgent problems of modern cardiology. Many aspects of it are far from unambiguously interpreted solutions and standards. Until the end, the mechanisms of the formation of uncontrolled course of hypertension remain unexplored, which, in turn, leads to a restriction of the use of drug and non-drug methods in the treatment of this pathology. Rational choice of antihypertensive therapy regimens can significantly improve the quality of treatment of this category of patients.
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The age is one of the main non-modified factors which reduces the elasticity of vessels and increases the appearance of atherosclerotic plaques. A number of studies have revealed that in some people, vascular changes occur at a younger age, while the presence of only classical risk factors does not explain the development of cardiovascular events in young people. This phenomenon is described as a syndrome of early, or accelerated, vascular aging (EVA). Aspects of this premature process include endothelial dysfunction, increased arterial stiffness, thickening of the intima-media complex and impaired dilatation of the central arteries, an increase of the reflected wave, hypertrophy of small vessels with a decrease in their lumen. Accelerated aging of the vascular wall increases the frequency of complications, therefore, recently "vascular age” is considered as an important predictor of individual risk of cardiovascular events. The review describes factors and mechanisms that trigger the process of EVA, genetic aspects of vascular damage and the biology of telomeres. Changes in hemodynamics and structural and functional properties of arteries during physiological and accelerated aging are presented. Currently, several indicators have been proposed that indicate arterial wall damaging and progression of vascular aging. The carotid-femoral pulse wave velocity is included in the list of indicators of subclinical target organs damage in ESH-ESC Guidelines for the management of arterial hypertension. The results of studies on the developing the new diagnostic markers for identifying individuals with "normal" or "early" ("accelerated") vascular aging are presented. Therapeutic strategies are aimed at decreasing the influence of factors that provoke EVA and include a non-pharmacological approach and medical intervention. The paper describes methods of therapeutic correction of the EVA syndrome.


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The most important issue of modern pharmacotherapy is not only efficacy, but also the safety of medicines. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is one of the main methods of treating acute and chronic pain in a wide range of diseases and pathological conditions. However, the prescription of this group of drugs requires consideration of the potential risks of complications, including from the side of the cardiovascular system. The purpose of the review was to assess the adverse reactions of the cardiovascular system when taking NSAIDs and approaches to their reduction. The article presents data on the mutual potential impact of cardiovascular diseases and musculoskeletal system, presents the results of large-scale studies of Russian and foreign authors and meta-analyzes of the NSAIDs effect on blood pressure profile, development of myocardial infarction, stroke and heart failure. The possible pathogenetic mechanisms of the side effects of NSAIDs are reviewed; the complexity of managing comorbid patients is demonstrated; it is shown that symptomatic treatment of pain and inflammatory syndrome should be carried out considering a personalized approach to the patient and rational choice of drugs.

Before the NSAIDs prescription, it is necessary to consider all cardiovascular risk factors with the determination of the total risk of cardiovascular complications. In patients with a very high cardiovascular risk, the use of any NSAIDs should be avoided; with high and moderate risk, the use of NSAIDs with the most favorable cardiovascular safety profile is possible. If the patient belongs to the category of low total coronary risk, the doctor can choose any NSAIDs. 



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ISSN 1819-6446 (Print)
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