Rational Pharmacotherapy in Cardiology

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Vol 6, No 3 (2010)
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In the issue.


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Homoeopathy in the era of evidence based medicine.


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Aim. To evaluate association of clinical and genetic factors with left ventricle hypertrophy (LVH) in patients with arterial hypertension (HT).

Materials and methods. 672 patients with HT were involved, aged 50,6 y.o. in average, men 67%. Laboratory assays, ECG, echocardiography were performed. Control group included 184 healthy persons. Genotyping with single-nucleotide substitutions of the endothelial NO synthase (eNOS) Glu298Asp gene, the C242T of the NADPH oxidase p22phox subunit and the angiotensin 2 receptor type 1 А1166С gene was carried out using a polymerase chain reaction (PCR) with evaluating of restriction fragments length polymorphism, while with substitutions of the angiotensinogen М235Т, G(-6)A gene allele-specific PCR “in real time” was applied.

Results. LVH was found in 39% of patients. It was more frequent in persons above 50 years old (OR 2,8, р<0,0001), in men (OR 1,43, p=0,035), in HT of degree 2-3 (OR 3,35, р<0,0001), HT duration more than 5 years (OR 2,52, р<0,05), in obesity (OR 1,57, р=0,005) or diabetes (OR 3,33, р<0,0001) presence. At genetic factors evaluation decrease of LVH risk was revealed in persons with the MM polymorphism of the angiotensinogen М235Т gene (OR 0,506, р=0,0187). Association of the MM genotype with LVH risk lowering was more obvious at the young age (OR 0,31, р=0,018). The A allele of the eNOS gene Glu298Asp polymorphism increased risk of LVH development when HT was diagnosed in the young age (OR 1,98, р=0,037) and in women up to 50 years old (OR 2,34, р=0,027). The T allele of the p22phox NADPH oxidase gene С242Т polymorphism correlated with LVH risk reduction in HT patients up to 50 years old (OR 0,6, p=0,01), the C allele – with increase of it (OR 1,66, р=0,01), this influence was more noticeable in women up to 50 years old (T allele – OR 0,21; C allele – OR 4,57, p=0,001).

Conclusion. Hypertensive LVH correlates with age, male gender, HT degree and duration, obesity and diabetes mellitus. Genetic factors were less associated with LVH.

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Aim. To study the correlation of the renin-angiotensin-aldosterone system (RAAS) activity with the female sex hormone levels and markers of target organ damage in patients with arterial hypertension (HT).

Material and methods. Patients with HT (20 men and 39 postmenopausal women) were involved into the study. The dynamic renal angioscintigraphy and echocardiography were performed, plasma rennin activity (PRA), levels of aldosterone, estradiole and 17-hydroxiprogesterone were determined by radioimmunoassay.

Results. Higher aldosterone level was found in women in comparison with men (212,5±123,9 pg/ml and 148,9±82,5 pg/m, respectively, р=0,03). Negative relations between aldosterone and estradiol levels (r=-0,3; p=0,04), and between aldosterone and 17-hydroxyprogesterone levels (r=-0,318; p=0,04), and positive relations between aldosterone concentration and PRA (r=0,555; p=0,04) was found in women. Besides, correlation between levels of female sex hormones, aldosterone and renal blood flow indicators, glomerular filtration rate, left ventricular mass index (LVMI) were found in women. These correlations were not found in men.

Conclusion. The gender differences of RAAS activity were revealed with higher aldosterone level in postmenopausal hypertensive women in comparison with men. Relationships between PRA, levels of aldosterone and female sex hormones and renal blood flow indices, LVMI were also found in women.

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Aim. To evaluate the anemia prevalence and its impact on chronic heart failure (CHF) course.

Methods. A total of 228 outpatients (86 women and 196 men, aged 39-85 y.o.) with clinically stable CHF (II-IV functional class according to NYHA) were studied. Anemia was defined by the WHO criteria (hemoglobin levels <13 g/dl in men and <12 g/dl in women).

Results. Anemia was found in 18,8% of CHF patients. In all the cases anemia was mild (hemoglobin levels >9 g/dl). Anemia rate did not differ significantly in patients with reduced (18,5%) and preserve (19,1%) or left ventricle ejection fraction (LV EF) (р=0,743). Anemic and non anemic patients were similar in terms of gender, NYHA functional class, heart rate and LV EF. The rate of anemic patients increased significantly up to 35,8% in creatinine clearance <60ml/min. Anemic patients were older (p<0,001), had longer CHF duration (p=0,014), lower body mass index (p=0,041), had diabetes more often (p=0,004, χ2=8,01) in comparison with non anemic patients. Deficiency of iron, vitamin B12 or folic acid was a reason of anemia in 35,8%, 9,4% and 15,1% of patients, respectively. Anemia reason was not detected in 39,7% of patients.

Conclusion. Anemia in patients with CHF is associated with age, impaired renal function, diabetes and high hospitalization rate because of CHF deterioration.

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Aim. To evaluate an efficacy of the 24-week antihypertensive therapy based on the carvedilol or metoprolol and its influence on markers of blood oxidative status in hypertensive patients with overweight/obesity.

Material and methods. The observation data of 20 hypertensive patients (aged 40-65 y.o.) with overweight/obesity were analyzed. Blood pressure (BP) dynamics at each visit and a rate of target BP achievement were evaluated. Blood oxidative status was evaluated by plasma malondialdehyde (MDA) level and erythrocyte superoxide dismutase (SOD) activity. Therapy safety was evaluated by adverse events registration.

Results. Significant reduction in both systolic and diastolic BP compared with baseline values was found. BP targets were achieved in all patients in both groups. The therapy based on carvedilol had a greater effect on blood oxidative status in comparison with metoprolol therapy. Plasma MDA level reduced from 7.03 [6.49;7.41] to 3.23 [2.88;3.57] μM/l (p<0.05) vs from 6.95 [6.51;7.39] to 6.08 [5.46;6.71] μM/l, respectively, and erythrocyte SOD activity increased from 27,89 [25.29;30.49] to 40.18 [35.89;44.45]% (p<0.05) vs from 28.41 [25.18;31.64] to 33.45 [30.65;36.23]%, respectively.

Conclusion. The high antihypertensive efficacy, positive effect on blood oxidative status and well tolerability of therapy based on carvedilol in everyday clinical practice is presented.

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Background. Being able to attenuate pathological remodeling, ACE inhibitors are considered to be first line medications for chronic heart failure (CHF) treatment.

Aim. To study the influence of the 6-month combined therapy with lisinopril on the heart and vessels remodeling in patients with ischemic CHF.

Material and Methods. 40 patients with CHF after Q-myocardial infarction were treated with lisinopril (Listril, Dr.Reddy’s, India) as a part of complex therapy. Initially and after 6 months of therapy the following findings were evaluated: the 6-minute walk test results, echocardiography parameters, main arteries rigidity, endothelium-dependent and independent vasodilatation, anticoagulant and fibrinolytic function of vascular endothelium, von Willebrand factor (VWF).

Results. 6-month treatment with lisinopril showed reduction in CHF functional class in 30 % of patients and increase in left ventricle (LV) stroke volume by 3,8% and LV ejection fraction by 1%. Pulse-wave velocity reduced insignificantly from 10,2 to 9,2 m/sec and augmentation indices of aorta from 31,4% to 29,9% as well as this of brachial artery from -2,6% to -6%. Endothelium-dependent vasodilatation increased from 6,4% to 8,6% and independent vasodilatation – from 13,8% to 16,6%. VWF activity decrease was observed in 40% of CHF patients. Significant changes in anticoagulant and fibrinolytic function of vascular endothelium were not revealed.

Conclusion. Lisinopril administration as a part of complex therapy of CHF patients during 6 months resulted in favorable effect on heart and vessels remodeling and was well tolerated.

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Aim. To find echocardiographic indicators of the heart remodeling which provide the best evaluation of chronic heart failure (CHF) severity in post-myocardial infarction patients.

Material and methods. Patients (n=100) with CHF related with ischemic heart disease (post-myocardial infarction) have been examined. The CHF severity was assessed by Scale of Clinical State Evaluation (SCSE) in V.Yu. Mareev's modification and 6-minute walk test. The echocardiography was performed with registration of the heart cavities size, left ventricle (LV) myocardium mass, LV asynergy index, LV sphericity index, time of LV isovolumic contraction and relaxation, Е/А ratio for mitral flow, grade of valvular regurgitation and pulmonary hypertension.

Results. The maximal correlation values of CHF severity was observed with intensity of diastolic dysfunction, systolic LV size and volume, LV asynergia index, integrated systolic remodeling index, degree of mitral regurgitation. Correlation value of CHF severity with LV ejection fraction was less than this with above mentioned indices.

Conclusion. The early echocardiographic markers of CHF were found. These are LV systolic sphericity index, LV integrated systolic remodeling index, LV systolic myocardial stress.

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Aim. To study effect of fluoxetine on sleep architecture in patients with metabolic syndrome and obstructive sleep apnea syndrome.

Material and methods. 98 patients with obstructive sleep apnea syndrome and metabolic syndrome (aged 54.3±8.7 y.o.) were included into the study. All patients received fluoxetine 20 mg once daily during 6 months. Influence of fluoxetine on sleep architecture was evaluated with special questionnaire and by polysomnography, including electroencephalogram, electrooculogram, mentalis electromyogram and pulseoxymetry.

Results. Decrease in wake time after sleep onset (Δ33%; р<0.05) was found at the end of treatment. It resulted in improvement of sleep efficacy index. Decrease in respiratory sleep disorders index (Δ20%) and rising of blood oxygen saturation (Δ12%; р<0.05) was also found. Improvement of the sleep architecture (reduction in the 2nd phase of slow wave sleep by 15%, increase in delta-sleep (Δ71%) and rapid eye movement sleep (Δ25%; р<0.05) was also observed. Besides reduction in body mass index after fluoxetine therapy (Δ12%; р<0.05) was found. Serious adverse effects were not registered.

Conclusion. Fluoxetine use in patients with metabolic syndrome and obstructive sleep apnea syndrome shown positive effect on objective indices of sleep architecture and respiratory sleep disorders. It improved adaptive function of the sleep and contributed to reduction in sleep disorders.

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Aim. To study antihypertensive efficacy and safety of amlodipine maleate as well as its influence on respiratory function, C reactive protein plasma level, glucose and lipid metabolism in patients with arterial hypertension (HT) and chronic obstructive pulmonary disease (COPD).

Material and methods. 50 patients with HT 1-3 grade and COPD I-II stage in remission were randomized into two groups. 31 patients of the first group were treated with amlodipine maleate (Stamlo-M) 5-10 mg/d alone or in combination. 19 patients of the second group received any other antihypertensive therapy except dihydropyridine calcium antagonists.

Results. Amlodipine in combined therapy has high antihypertensive efficacy providing achievement of target blood pressure levels and improvement of 24-hour blood pressure profile. Amlodipine therapy improved respiratory function and reduced systolic blood pressure in pulmonary artery. Amlodipine has no negative influence on metabolic status, did not increase sympathetic activity, and reduced C reactive protein levels. It demonstrated good tolerability and safety.

Conclusion. High antihypertensive efficacy, improvement of respiratory function, and safety allows recommending amlodipine maleate (Stamlo-M) for usage in hypertensive patients with COPD.

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Aim. To evaluate quality of life changes and compliance to therapy in patients following successful transluminal angioplasty, who have indications for fluvastatin extended release in addition to standard treatment.

Material and methods. This is a national observational multicenter study. An inclusion of 60 investigator centers is planned (out-patient medical centers), the total number of patients to be included is 600. Patients (men and women) with coronary heart disease following successful transluminal coronary angioplasty, who were prescribed fluvastatinextended release (Lescol Forte, Novartis) 80 mg once daily will be included in the observation. The following efficacy and safety parameters will be evaluated: quality of life assessed with SF-36 scale before and during treatment; compliance to therapy; adverse events and serious adverse events. Observation period is planned for 6 months. During this period patient is expected to make 4 visits to treating physician. According to the physician’s decision, observation period can be extended to 12 months.

Present study status. The study is completed. 524 patients completed the observation, including 116 patients who were followed up for 12 months. There are 414 men (79%) and 110 women (21%) among patients enrolled into the study.

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Early diagnostics and treatment of patients with acute rheumatic fever (RF) remains actual problem because rheumatic heart disease is still one of the main causes of acquired valvular lesions. Two cases of acute RF occurred in City Clinical Hospital №1 named after N.I. Pirogov in 2009 are presented. Different outcomes were observed during 6 and 10 months of clinical monitoring. The main approaches to diagnostics and treatment of RF are also described taking into consideration national and international guidelines.

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Amiodarone is one of the basic antiarrhytmic drugs for atrial fibrillation treatment. However application of amiodarone in patients with atrial fibrillation and Wolff-Parkinson-White syndrome can induce ventricular fibrillation. Amiodarone usage in these patients should be accompanied by readiness for performance of resuscitation. This is confirmed by clinical case presentation.


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Details of pre-hospital medical care organization in patients with acute coronary syndrome (ACS) with ST segment elevation are discussed. The algorithm of pre-hospital diagnostics and emergency cardiac care to these patients is presented. The necessary methods of examination, drugs and their dosages are specified. The importance of reperfusion as a key approach to ACS patients treatment is emphasized. Advantages and disadvantages of reperfusion therapeutic methods and algorithm of their choice are presented.


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Relationship of metoprolol clinical efficacy with its different salts (tartrate, succinate, fumarate) as well as its presentations (tablets with immediate, controlled or sustained release) is analyzed. It is highlighted that pharmacodynamic properties depend on metoprolol molecule only. These properties do not change after modification of drug presentation or metoprolol plasma concentration which depends on velocity of drug release from the tablet. Data of randomized clinical trials are discussed in regard to development of evidence base for use of different metoprolol presentations in treatment of patients with arterial hypertension, unstable angina, myocardial infarction, heart failure. Indications for tartrate and succinate salts of metoprolol are presented. Results of clinical studies on efficacy of metoprolol tartrate in long-acting drug presentations are analyzed.

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Aim. To study the influence of complex homeopathic drug ubichinon compositum on hemodynamics, Na,K-ATPase activity, parameters of oxidative stress and serum nitric oxide (NO) metabolites concentration in experimental diabetes mellitus.

Materials and methods. Diabetes mellitus was induced by the administration of 5% alloxan solution to 75 rats, 15-18 mg/100 g of body weight; 20 rats without diabetes comprised control group. The parameters of macro- and microhemodynamic, lipid peroxidation, Na,K-ATPase activity, and stable NO metabolites concentration have been compared in animals with experimental diabetes mellitus under 1 month administration of ubichinon compositum (0,11 mg/100g of body weight).

Results. Experimental diabetes mellitus was shown to be associated with the development of oxidative stress expressed as activation of lipid peroxidation — increase of maloniс dialdehyde (MDA) concentration both in serum and cortex and medulla substances of renal tissues. At the same time, the antioxidant potential as well as the endothelial function (assesed as NO metabolites concentration) were decreased as compared with control animals. Administration of ubichinon compositum for 1 month resulted in restoration of stable NO metabolites concentration and Na,K-ATPase activity, as well as reduction of lipid peroxidation in blood and renal tissues

Conclusion. The administration of ubichinon compositum resulted in reduction of hemodynamic manifestations of microvascular complications of diabetes mellitus.


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Comments to the guidelines.


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To the 50-th anniversary of the birth of Prof. Sergey Nikolayevich Tereschenko.

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Russian National congress of cardiology in October 5-7, 2010.

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Report on scientific and educational forum “Preventive cardiology 2010”.

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Russian-Indian epidemiology project.

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Russian National Congress “Man & Drug”. Moscow, April 14, 2010. Interactive discussion “Painful points of contemporary cardiology: honest answers to the thorny questions”.

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)