Rational Pharmacotherapy in Cardiology

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Vol 10, No 1 (2014)
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6-17 741

Aim. To evaluate in a prospective 10-year follow-up study cardiovascular mortality rate in a population of middle-aged men with different levels of total cardiovascular risk, and correlation between combinations of risk factors (RF) and the extent of coronary atherosclerosis according to autopsy reports of subjects who have died of ischemic heart disease (IHD) undiagnosed during life-time. To estimate the efficacy of multifactor primary prevention.

Material and methods. The analysis was based on the results of the “Multifactor ischemic heart disease prevention” prospective controlled study of two 40-59-year-old men populations (1preventive measures, 2 – a group of comparison). Standardized epidemiological examination using unified protocol was performed in the total of 6656 people. The article presents results of prospective follow-up of the two groups, participants of which did not initially have  IHD clinical signs: the group 1 – n=2975, the group 2 – n=2705. Active correction of IHD RF (high blood pressure, hypercholesterolemia, overweight, smoking, low physical activity) in the group 1 lasted for 5 years; the whole period of follow-up was 15 years. At that, end points (all-cause mortality, myocardial infarction and stroke) were estimated and verified in each case. This article evaluates the 10-year follow-up period.

Results. Prevention in middle-aged men population allowed significantly to reduce levels of the major RF and total cardiovascular risk by 38.1%. In the absence of preventive measures cardiovascular risk, predicted by the SCORE chart, already realizes during the first 5 years. In fact cardiovascular mortality rates during 10-year follow-up exceed the risk predicted by the SCORE chart. Active primary IHD prevention allows to reduce the risk of cardiovascular death in men with initially high risk – by 36.9% and with initially very high risk – by 43.4%. Men, who have died of IHD undiagnosed during life-time, with combination of 3 and more RF revealed coronary artery stenosis of multiple localization in 91.7%, with 2 RF – in 89.6% and with singular RF – in 78.3% of the cases.

Conclusion. We proved substantiated the relevance of multifactor primary prevention of atherosclerosis-mediated cardiovascular diseases. Primary medical prevention has demonstrated its effectiveness, especially at high cardiovascular risk, and particularly evident at a long-term follow-up. For the first time ever long-term prospective follow-up study of the population with standardized assessment of health parameters revealed negative predictive value of multiple RF in respect to coronary atherosclerotic lesions estimated postmortem.

18-24 585

Aim. To study the relationship between heart rate variability (HRV) and components of the metabolic syndrome (MS) in women with rheumatoid arthritis (RA).

Material and methods. Female patients (n=291) with a firm RA diagnosis under 60 years of age were examined. Evaluation of traditional cardiovascular risk factors, MS components (International Diabetes Federation criteria), 24-hour ECG monitoring were performed along with the assessment of clinical symptoms, the degree of activity and severity of RA.

Results. Weak associations of HRV with waist circumference, blood pressure level, hypertriglyceridemia, hypoalphalipoproteinemia and smoking were found in the correlation analysis. Patients with RA were divided into three groups depending on the number of existing MS components. Group 1 (0-1 component) included 113 women (39%), group 2 (2-3 components) – 109 women (37%) and group 3 (4-5 components) – included 69 women with RA (24%). Progressive decrease in the absolute values and the increase in the percentage of the low values of all the studied time and frequency HRV indices, adjusted by age and heart rate, from the 1st to the 3rd group of women with RA were determined. Significant increase in sympathovagal index from the 1st to the 3rd group was also shown.

Conclusion. A combination of several components of the MS in RA plays a greater role in the development of disorders of neurovegetative autonomic control of heart activity (increased influence of the sympathetic and/or reduced influence of the parasympathetic nervous system on cardiac function) than each traditional cardiovascular risk factor taken separately. Abnormality in autonomic regulation of cardiac activity may be an important link in the pathogenesis of cardiac arrhythmias, sudden cardiac death and overall cardiovascular mortality in women with RA.

25-30 565

Aim. To study changes in the parameters of the 24-hour blood pressure (BP) monitoring and arterial stiffness (AS) in patients with arterial hypertension (HT) and chronic obstructive pulmonary disease (COPD) treated with angiotensin II receptors blocker, valsartan.

Material and methods. Men with HT and COPD (n=23), who have been receiving valsartan with starting dose 80 mg/day for 6 months as antihypertensive therapy were included into the study. If target BP was not achieved, correction of the valsartan dose was carried out with the hydrochlorothiazide addition when needed. Clinical examination, 24-hour BP and AS monitoring using BPLab MnSDP-2 monitor ("Petr TELEGIN",Russia), clinical evaluation of COPD were performed.

Results. Abnormal circadian BP profile and the elastic properties of arteries were diagnosed in the majority of hypertensive patients with COPD. Valsartan therapy allowed to achieve target BP levels in 100% of patients, normalization of circadian BP profile in 56.5%, improvement in AS parameters: a significant increase in PTT2 (from 89.6±14.3 to 94.4±18.4 ms), reduction of (dP/dt)max (from 566.6±117.9 to 518.8±146.2 mmHg/s), AIx (from -4.0±15.2 to -11.6±20.8 %) as compared to the baseline. Circadian changes in daily parameters of AS in studied patients with the most obvious night-time abnormalities of the elastic properties of arteries were detected. Valsartan intake led to Alx reduction at night-time.

Conclusion. Valsartan-based therapy in hypertensive patients with concomitant COPD demonstrated a high antihypertensive efficacy and favorable changes in the elastic properties of the vascular wall that confirm its organoprotective effect.

31-36 501

Aim. To study the characteristics of renin profile and parameters of central pulse wave and arterial stiffness in patients with previously untreated arterial hypertension (HT). Material and methods. Patients (n=83;  39 males (47%); age 57.3±7.6 years) with untreated uncomplicated 1-2 degree HT without associated clinical conditions and diabetes, with glomerular filtration rate>60 ml/min/1.73m2 were enrolled into the study. Plasma renin activity (PRA), plasma renin level and angiotensin II level were evaluated. The analysis of the central pulse wave, and pulse wave velocity (PWV) measurements were performed.

Results. The incidence of volume-dependent HT (PRA <0.65 ng/mL/h) was 69%, and the renin-dependent HT with normal PRA (0.65-6.5 ng/ml/h) – 31% in patients with untreated uncomplicated HT. Patients with low PRA are characterized by older age, higher systolic blood pressure (BP) and higher arterial stiffness (increased PWV, increment pressure, augmentation index with a decrease in pulse pressure amplification) after adjustment for these factors.

Conclusion. The presence of volume-dependent HT is associated with older age, higher level of systolic BP and increase in arterial stiffness independent of age and BP.

37-42 511

Aim. To assess the role of the activation of matrix metalloproteinase-1 zymogen (ProMMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the development of left ventricular (LV) hypertrophy in patients with arterial hypertension (HT) and metabolic syndrome (MS) with varying degree of obesity.

Material and methods. 108 patients with HT and MS divided into 3 groups according to body mass index, and 28 healthy women were studied. Intracardiac blood flow and ProMMP-1 and TIMP-1 levels were assessed.

Results. Disbalance in the ProMMP-1 and TIMP-1 systems  is associated with the severity of left ventricular remodeling and grade of obesity. The changes in LV structure and geometry and activation ProMMP-1 with a deficit of TIMP-1 were most significant in patients with HT and grade 3 obesity (respectively 7.7±0.61 and 183.6±17.2 ng/ml in grade 3 obesity vs 3.5±0.3 and 291.7±22.4 ng/ml in grade 1 obesity; p<0.05). Associations between hemodynamic parameters and levels of ProMMP-1 [withLVmass index (LVMI): r=0.47; p<0.05] and TIMP-1 (with LVMI: r=-0.39;  p<0.05) were determined.

Conclusion. Changes in the ProMMP-1 and TIMP-1 system in women with HT and MS are associated with the severity ofLVhypertrophy.

43-48 971

Aim. To study meldonium effect in the combination therapy for ventricular repolarization disorders and cardiac electrical instability in patients with ischemic stroke.

Material and methods. Patients (n=46) with acute phase of ischemic stroke were included in a randomized, open-label, uncontrolled study. Patients were randomized into two groups. Group 1 patients (n=25) had been receiving meldonium (Mildronate;Grindex,Latvia;Pharmstandard,Russia), 1.0 g/day intravenously once daily, as a part of standard therapy for 10 days since admission to the hospital. Group 2 patients (n=21) had standard therapy alone. A standart 12-lead ECG, ventricular late potentials (VLP), 24-hour Holter monitoring, troponin test were performed at the baseline and after 10 days.

Results. Patients of the group 1 as compared to the group 2 demonstrated more significant positive effect on the clinical condition of patients with ischemic stroke, ventricular repolarization, reduction of frequency (from 3.7±0.5 to 2.1±0.4; p<0.05) and duration (from 6.6±1, 3 to 4.0±1.1 min; p<0.05) of painless myocardial ischemia episodes and VLP (from 48 to 32%).

Conclusion. Adding meldonium to standard therapy in patients with acute phase of ischemic stroke can have a positive effect on the clinical condition, repolarization disorders on ECG, frequency of VLP and episodes of painless myocardial ischemia detection. This may have a positive effect on the electrical stability and prevention of cardiac arrhythmias. 


49-54 501

Hypertrophic cardiomyopathy belongs to a group of hereditary diseases due to sarcomere gene mutation. This abnormality is characterized by the development of symmetric or asymmetric hypertrophy of left ventricular myocardium with its normal contractile function or hypercontractility. Authors provide a brief overview of variants of hypertrophic cardiomyopathy and phenocopies of this disease, when structural changes in the heart are not the result of classic sarcomere gene mutation. In patients with some phenocopies concentric left ventricular hypertrophy can transform into its dilatation with reduced contractility. Such variant of hypertrophic cardiomyopathy is presented in the first clinical observation. The second case shows that hypertrophic cardiomyopathy can be one of the symptoms of the disease with other reasons for poor outcome.

55-61 664

Aim. To study the subjective opinion of patients and doctors about their individual experiences with adherence to treatment for chronic cardiovascular diseases in the group focused interview of patients and their physicians.

Material and methods. 3 groups of patients from clinical studies adhering to the doctor's recommendations (focus-group 1) and 3 groups of patients hospitalized for cardiovascular events, not adhering to recommendations after discharge (focus-group 2) and one focus-group of doctors were analyzed. Group discussion was performed by a moderator (experienced sociologist, with no medical training who was not familiar with the patients and physicians).

Results. 47 patients (25 (53.2 %) men and 22 (46.8%) women) and 6 doctors participated in the study. Paternalistic model of communication with doctors present in the minds of all patients. In patients of the first group this results in a full confidence in the doctor and compliance with all recommendations while in patients of the second group lack of care in the outpatient clinic makes them "offended" by the underestimation of their trust and causes non-compliance. Physicians intuitively divide patients into less and more "attractive" for themselves. This "division" on the one hand may have some predictive value in respect of patients’ adherence to a further treatment, and on the other hand, the "doctors’ prejudice" in relation to the patient may adversely effect the behavior of the patients and failure to follow the recommendations in the future.

Conclusion. The significant paternalism on the part of the patient on the one hand increases the responsibility of the physician for his patient, and on the other hand – increases opportunities for his influence on the patients’ behavior.


62-72 489


Aim. To develop a comprehensive clinical and morphological approach to the nosological diagnosis and treatment of "idiopathic" arrhythmias (IA) and the syndrome of dilated cardiomyopathy (DCM).

Material and methods. Patients (n=320) with IA (n=190; 117 women, age 45.3±14.8 years) and DCM (n=130, 41 women, age 46.9±12.5 years) were included in the main group. 51 people (patients with ischemic heart disease; heart valve disease, hypertrophic cardiomyopathy, who underwent open-heart surgery; healthy volunteers) were included in the control group. Along with the standard tests evaluation of the level of anti-heart antibodies (185 patients with IA and 122 with DCM), viral serology (166 and 122), multispiral computed tomography (42 and 88), cardiac magnetic resonance imaging (41 and 22), coronary angiography (19 and 54), myocardial biopsy/autopsy (19/0 and 33/9) were performed.

Results. According to morphological study infectious-immune myocarditis was found in 78.9% of IA and 66.7% of DCM-patients, arrhythmogenic right ventricular dysplasia in 5.3% and 4.8% of patients, respectively. Other genetic cardiomyopathies, including combination with myocarditis were revealed in other patients. The frequency  of the viral genome detection in the myocardium in IA, DCM and the control group was 17.6%, 66.7% and 77.1%, respectively. However in the control group the incidence of myocarditis and anti-heart antibodies titers were significantly lower, while in the main group a strong correlation between myocarditis and anti-heart antibodies titers was found. The algorithm of noninvasive nosological diagnostics was developed; it allowed to verify diagnosis in 95% of IA patients and 89% DCM patients.

Conclusion. Nosological cause of IA and DCM syndrome can be diagnosed in most patients by using an integrated clinical and morphological approach.


73-78 495

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare life-threatening disease with a prevalence of 2 cases per 100000 population. CTEPH is a chronic, progressive disease characterized by high disability and mortality rates in young and middle-aged people, often with underlying genetic and autoimmune thrombophilic disorders. The need for pathogenetic therapy with orphan drugs that can slow the progression of the disease is supported.

79-82 1743

The article considers the questions of the relationship between the amount of the consumed alcohol, the type of alcoholic beverage, pattern of alcohol consumption and the blood pressure level. The article presents data on the positive effect of alcohol intake restrictions and recommendations for permissible limits of alcohol consumption. New possibilities of drug therapy aimed at limiting alcohol consumption are being reported.

83-91 872

Chronic kidney disease (CKD) is associated with increased cardiovascular risk. CKD is characterized by accelerated aging of vessels in which the age-related arterial stiffness increase is exacerbated by a number of uremia-related processes. Increased arterial stiffness is associated with structural and functional disorders, as well as with the increase in cardiovascular mortality in patients with CKD. Increased arterial stiffness is diagnosed at an early stage of CKD. Modern understanding of the mechanisms of increased risk of cardiovascular complications in CKD, the factors contributing to the loss of elasticity of the arteries, arterial stiffness increase consequences are analyzed. Data illustrating the twoway interaction between CKD and arterial stiffness and mechanisms of accelerated progression of arterial stiffness in CKD are presented.

92-98 572

Data about the current approach to the choice of dual antihypertensive combinations in various clinical situations for treatment of hypertension are presented. Advantages and indications for the combination of an ACE inhibitor with a dihydropyridine calcium channel blocker are reviewed. Data from prospective studies on the efficacy and safety of combination of third generation calcium channel blocker lercanidipine with ACE inhibitor enalapril are presented.


99-105 704

Progression of cardiovascular disease is often caused by a deficiency of magnesium in the human body. Magnesium belongs to the necessary vital macronutrients providing many physiological and pathological reactions and is involved in the constructive, energy, electrolyte metabolism. Correction of magnesium deficiency is realized using magnesium-containing drugs, for example magnesium orotate, having pleiotropic effects due to independent metabolic activity of orotic acid.

106-115 679
Translation articles:

R. Eschalier, J.J.V. McMurray, K. Swedberg, D.J. van Veldhuisen, H. Krum, S.J. Pocock, H. Shi, J. Vincent, P. Rossignol, F. Zannad, B. Pitt, for the EMPHASIS-HF Investigators “Safety and Efficacy of Eplerenone in Patients at High Risk for Hyperkalemia and/or Worsening Renal Function. Analyses of the EMPHASIS-HF Study Subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure)”  J Am Coll Cardiol 2013;62(17):1585-93;


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