The paper is focused on the results of a randomised clinical trial SHIFT, which started the discussion about the choice of optimal heart rate-lowering therapy in patients with chronic heart failure (CHF). The author summarizes the benefits of adding an If channel inhibitor ivabradine to the standard CHF therapy and presents the place of this medication in the modern clinical guidelines on CHF management.

 

Aim. To investigate the parameters of systolic function in patients with acute Q-wave myocardial infarction (AMI), comparing the results of two-dimensional echocardiography (2D EchoCG), three-dimensional real-time EchoCG (3D EchoCG), and computed tomography (CT) as a verification method. To study the parameters of dyssynchrony, which develops due to mechanic myocardial heterogeneity in AMI patients. Material and methods. In total, 82 patients (61 men and 21 women; mean age 52±21 years) were examined within the first 6 days of AMI. The comparison group, comparable by age and sex, included 65 individuals without clinically manifested cardiovascular pathology. All participants underwent standard examinations, electrocardiography (ECG), 24-hour ECG monitoring, EchoCG, angiography, and CT. Mechanic dyssynchrony was assessed by dispersion of the time to the minimal volume of 16 segments (strain dyssynchrony index, SDI). Results. The difference for end-diastolic volume (EDV; 2D vs. 3D EchoCG and 2D EchoCG vs. CT) was statistically significant (respective p-values 0,014 and <0,005). Ejection fraction (EF) and local contractility index (LCI) were significantly different for 2D vs. 3D EchoCG (>p=0,0002 and <0,005, respectively). EF values were similar for 3D EchoCG and CT (>p=0,3). SDI values in AMI patients were significantly higher than in the comparison group participants (6,8±2,7% vs. 2,9±1,6%; p<0,001). In patients with anterior AMI, the SDI differences were observed for one vs. two-vessel (p<0,05) and one vs. three-vessel pathology (>< 0,05) and one vs. three-vessel pathology (p<0,005), but not for two vs. three-vessel pathology.><0,005), but not for two vs. three-vessel pathology. Patients with inferior AMI did not demonstrate any marked differences in SDI values. Among patients with SDI >5,1, the incidence of clinical complications (pulmonary edema, ventricular fibrillation, high-grade atrioventricular block) was higher by 55% (p<0,05; ><0,05 r=0,35). SDI was also associated with high-grade ventricular arrhythmias (p<0,005; ><0,005r=0,48). Conclusion. Three-dimensional visualization provides an opportunity to assess systolic function parameters more accurately. SDI values were linked to the number of affected coronary vessels. The significance of the observed differences was related to AMI localization. SDI could be regarded as a determinant of both mechanical myocardial heterogeneity and the risk of clinical and arrhythmic complications in AMI.

 

 

 

 

Aim. To study the factors associated with elevated D-dimer levels in patients with acute venous thromboembolic events (VTEE).
material and methods. The study included 111 patients (76 men and 35 women aged 18–76 years) with a first or repeat episode of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in the last 2 months. The majority of the patients (n=80) received unfractionated heparin (UFH) for at least 5 days, followed by warfarin (international normalized ratio (INR) control at least once a month; target INR 2,0–3,0). Some patients (n=31) received therapeutic doses of enoxaparin (1 mg/kg subcutaneously, every 12 hours) for at least 30 days, followed by warfarin treatment. D-dimer levels (norm <0,5 mkg/ml) were measured by the latex agglutination method, with the use of “STA LIATEST >® D-DI” reagents (Diagnostica Stago). Results. D-dimer levels varied from 0,02 to 9,96 mkg/ml (median 1,05 mkg/ml, interquartile range 0,49–1,99 mkg/ml) and exceeded the upper norm limit in 74% of the patients. There was a positive association between D-dimer levels and thrombus “size” (r=0,304; p<0,001), and a negative association between D-dimer levels and >< 0,001), and a negative association between D-dimer levels and thrombus “age” (r=-0,418; p<0,001). Predictors of D-dimer elevation were identified among 150 demographic, anthropometric, anamnestic, clinical, laboratory, genetic, or ultrasound parameters and VTEE risk factors. The results of the multivariate stepwise regression analysis demonstrated that female gender, chronic heart failure (CHF), VTEE symptom duration ><28 days, and thrombus “size” >< 0,001). Predictors of D-dimer elevation were identified among 150 demographic, anthropometric, anamnestic, clinical, laboratory, genetic, or ultrasound parameters and VTEE risk factors. The results of the multivariate stepwise regression analysis demonstrated that female gender, chronic heart failure (CHF), VTEE symptom duration <28 days, and thrombus “size” >< 28 days, and thrombus “size” < 6 points were independent predictors of D-dimer elevation in the acute period of DVT/PE. Conclusion. D-dimer levels, measured 32 (23–44) days after the development of DVT/PE symptoms, were elevated in 74% of the patients. D-dimer elevation in the acute period of VTEE was associated with female gender, CHF, “age” and “size” of the thrombus.

 

 

 

 

Aim. To study the effects of trait anxiety (TA) on the post-CABG (coronary artery bypass graft surgery) dynamics of cognitive function in patients with coronary heart disease (CHD). Material and methods. In total, 52 patients, aged 45–70 years, were divided into two groups: with moderate (n=24) and high (n=28) levels of TA. Results. The patients with high TA demonstrated worse cognitive function parameters 6 months after CABG, compared to the patients with moderate TA levels. Conclusion. High TA levels are one of the factors which negatively affect cognitive function parameters in CHD patients. These patients could be regarded at increased risk of post-CABG cerebrovascular complications.

 

 

Aim. To study psycho-emotional and autonomic status, circadian blood pressure (BP) profile, and quality of life (QoL) in patients with metabolic syndrome (MS) and dyspepsia syndrome. Material and methods. We followed up 110 patients (66 women and 52 men), aged 20–60 years (mean age 47,5±2,1 years). The levels of anxiety and depression were assessed with Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating Scale (HDRS), respectively. Personality traits were assessed with the Freiburg Personality Inventory (FPI), eating behaviour with the Dutch Questionnaire of Eating Behaviour (DQEB), and QoL with the SF-36 questionnaire (version 1). Circadian rhythms of autonomic balance, BP, and electrocardiography (ECG) parameters were assessed via the 24-hour monitoring of heart rate variability (HRV). The assessment of BP and ECG was performed with the use of “Cardio-Tens-01” device (Meditech, Hungary) and the subsequent data analysis with the “Medibase” software. Statistical analysis was performed using the Windows software Microsoft Excel 5.0 and Statistica 6.0.
Results. Affective disorders, personality disorders, and QoL disturbances were more pronounced in the patients from Group 4, who had MS and dyspepsia syndrome. The results of the 24-hour BP monitoring demonstrated that mean daytime and nighttime levels of diastolic and systolic BP for Group 2 (dyspepsia syndrome plus arterial hypertension, AH) were higher than for Group 4 (dyspepsia syndrome, obesity, and AH). Mean levels of BP variability parameters were higher for Group 4 than for Group 2. However, these differences between the groups were not statistically significant. The patients with obesity, AH, and dyspepsia syndrome (Group 4) demonstrated minimal circadian HRV dynamics, which might be due to a reduced adaptive potential in these individuals. Conclusion. The majority of the participants had substantial psycho-emotional disturbances, autonomic dysbalance (sympathetic hyperactivation), and desynchronosis, which were closely related to other parameters and more manifested in patients with the combination of MS and dyspepsia syndrome. This should be taken into account when planning and performing preventive and therapeutic interventions.

 

 

Aim. To study the blood levels of insulin and glucose, to assess the prevalence of insulin resistance (IR), and to investigate the association between IR and the components of metabolic syndrome (MS) in a population sample of adolescents aged 14–17 years. Material and methods. A representative sample of Novosibirsk City adolescents, aged 14–17 years, was examined (n=667). The examination included the standard questionnaire survey, blood pressure (BP) measurement, anthropometry, and the assessment of serum levels of lipids, insulin, and glucose. Hyperinsulinemia (HI) was diagnosed if basal insulin levels were ≥15 μIU/ml, while fasting hyperglycaemia (FHG) was registered if fasting glucose levels were ≥5,6 mmol/l. IR was diagnosed if HOMA index was >3,7. Results. In Novosibirsk adolescents, the prevalence of IR reached 11,8% (13,4% in boys and 10,5% in girls). FHG was registered in 2% of boys and 0,8% of girls; the prevalence of HI was 22,5% and 21%, respectively. The presence of IR was associated with higher values of waist circumference, BP, blood triglycerides, body mass index, and lower levels of high-density lipoprotein cholesterol. The 90% percentile of HOMA distribution in this adolescent population sample was 4,1 (4,7 in boys and 3,7 in girls). Conclusion. The study results justify the need for a regular monitoring of carbohydrate metabolism markers in adolescents.

 

 

Aim. To study the effects of a thiazide-like diuretic indapamide (Ind) on the levels of free oxygen radicals generated by blood phagocytes and isolated neutrophils in patients with heart failure (HF). Material and methods. Using whole blood samples and isolated neutrophils of 16 HF patients (NYHA Functional Class II–III), the generation of free oxygen radicals was examined with a chemiluminometre “Biotox-7”, in the presence of luminophores – lucigenin (30 mkM) and luminol (50 mkM). The standard stimulators of blood phagocytes and neutrophils were bacterial tripeptide (FMLP, 3 mkM) and phorbol ester (PMA, 1 mkM). The generation of superoxide anions (O2-) and hydroxyl radicals was continuously assessed by the number of impulses per second and presented as integral chemiluminescence (summary value for 10 minutes). Inhibiting effects of varied Ind concentrations were assessed by the decrease (%) in the peak stimulated luminescence. Antioxidant activity of Ind was studied in the cell-free medium generating hydroxyl radicals. Statistical analysis of the data was performed with the use of SigmaPlot software. Results. At baseline, the blood of HF patients contained pre-activated (primed) phagocytes, as shown by the “spontaneous” production of superoxide anions due to neutrophil adhesion on cuvette walls. PMA markedly increased the production of oxygen radicals. In the neutrophil suspension, Ind dose-dependently (0,5–2 mkM) reduced the peak PMA response levels of superoxide anions up to the baseline levels. Moreover, Ind demonstrated a similar effect in whole blood samples of HF patients. FMLP increased the production of oxygen radicals and potentiated the subsequent response of phagocytes to PMA. Ind (2 mkM), when added after FMLP and PMA, reduced the post-stimulation levels of superoxide anions up to baseline values. The initial exposure of blood samples to Ind decreased spontaneous generation of oxygen radicals and the magnitude of subsequent response to FMLP and PMA. Antioxidant effects of Ind were also observed in the cell-free medium, which suggests a direct interaction between Ind and oxygen radicals. Conclusion. Low Ind concentrations provided a marked antioxidant effect, which could be clinically significant in the management of HF patients.

 

 

The pharmacoeconomic analysis compared the strategies of arterial hypertension (AH) management using different angiotensin II receptor blockers (ARB). The first stage of the analysis included the cost-effectiveness modelling in patients with moderate AH receiving olmesartan, losartan, or valsartan. As the second stage, a similar analysis was performed for patients with moderate AH and diabetes mellitus (DM) or renal failure. Clinical and economic benefits were demonstrated for olmesartan, compared to losartan or valsartan. The cost-effectiveness ratio was minimal for olmesartan therapy in patients with both moderate AH and a combination of moderate AH and DM or renal failure. Therefore, olmesartan should be considered as a first-choice medication while selecting the optimal clinical and pharmacoeconomic strategy of AH management with ARB.

 

 

Aim. To assess the antiischemic effectiveness of an If-channel inhibitor ivabradine and its impact on systemic and myocardial microcirculation, left ventricular diastolic dysfunction, and psychosocial parameters in patients with coronary heart disease (CHD) associated with chronic obstructive pulmonary disease (COPD).
material and methods. The study included 82 patients with CHD and Functional Class II–III stable angina. In 47,6% of the participants, CHD was associated with Stage 1–3 COPD. Results. It was demonstrated that the If-channel inhibitor ivabradine is the medication of choice for patients with a combination of CHD and COPD. Ivabradine therapy was both effective and safe, and did not negatively affect the clinical course of COPD.

 

 

Aim. To assess the adrenergic receptor activity and the effects of Magnerot therapy in patients with cardiac arrhythmias and connective tissue dysplasia (CTD).
material and methods. The study included 18–35-year-old patients with cardiac arrhythmias and CTD. In all participants, sympathoadrenal system activity was evaluated via beta-adrenoreceptor sensitivity. In particular, erythrocyte osmotic resistance was measured in the presence of beta-adrenoblockers (diagnostic kit “AGAT Med”, Moscow). Results. Patients with ectopic cardiac arrhythmias and CTD demonstrated increased erythrocyte hemolysis levels in the presence of beta-adrenoblockers, which suggested adrenoreceptor desensitisation in this clinical group. A four-month Magnerot treatment was associated with a significant reduction in desensitisation of erythrocyte beta-adrenoreceptors (p<0,0001). Conclusion. Magnerot therapy improved the adrenoreceptor sensitivity to adrenoblockers.

 

 

Aim. To assess the levels of residual platelet reactivity (RPR) and its potential correction by antiaggregant therapy in patients with angina. Material and methods. The study included 40 patients with coronary heart disease (CHD), aged under 70 years, with adequate blood pressure control and no contraindications for antiaggregant therapy. All participants underwent general clinical examination, general blood assay, blood biochemistry, and platelet aggregation assessment (blind method). ADP (5 mkmol/l) was used as an aggregation inductor. The patients were randomised into two groups, to compare the antiaggregant activity of aspirin (thrombo ASS 100 mg) vs. plagril (clopidogrel 75 mg), and plavix (75 mg) vs. plagril (75 mg). Platelet aggregation was assessed at baseline and at least three weeks later. After three weeks of the initial therapy, the patients were switched to another therapy arm (cross-over). Finally, all patients were receiving two antiaggregants (thrombo ASS and plagril). Results. During the therapy with enteric coated aspirin (100 mg), RPR above the target level (>46%) was observed in 72,5%. After switching to clopidogrel therapy, target RPR levels were achieved in almost 50% (n=16). Among remaining resistant patients (n=13; 32,5%), 8 achieved target RPR while receiving a combination of aspirin and plagril. Therefore, only 5 patients (12,5%) were resistant to both medications. Clopidogrel monotherapy did not reduce RPR to target levels in 14 patients (35%). In this group, aspirin was effective only in one patient. Conclusion. High RPR levels were more prevalent during the treatment with enteric coated aspirin (72,5%), compared to clopidogrel therapy (plagril or plavix; 35%; p<0,001). Only 12,5% of the participants were resistant to both medications (aspirin and clopidogrel). Overcoming this resistance could be possible with the use of new thienopyridine antiaggregants (prasugrel) or glycoprotein IIb/IIIa inhibitors.

This analytic paper presents the evidence on the potential of acetylsalicylic acid (ASA) for the mortality reduction in patients with cardiovascular disease. The focus is on the “minimal” effective dose of ASA, in terms of its effects on survival. The discussion of the ASA form and dose selection also mentions the impact of ASA tolerability on its effectiveness. The need for the balance between antiischemic effectiveness and safety (haemorrhage safety, in particular) justifies the use of varied ASA doses. The benefits of so-called enteric coated ASA forms are also summarised.

Angiotensin-converting enzyme (ACE) inhibitors are currently one of the most frequently used groups of cardiovascular medications. In addition to wellknown indications, such as arterial hypertension (AH), chronic heart failure (CHF), and Type 2 diabetes mellitus (DM-2), some ACE inhibitors could be used in other clinical situations. The medications with additional vascular activity (for example, perindopril A) have certain benefits, compared to other ACE inhibitors.

The prevalence of overweight and obesity is currently increasing worldwide. Obesity is a risk factor of cardiovascular disease and Type 2 diabetes mellitus. In obese individuals, metabolic, dyshormonal, and hemodynamic changes directly affect myocardial structure and function. Mitochondrial dysfunction and oxidative stress, insulin resistance and hyperglycaemia, dysadipokinemia, and direct lipotoxic effects of lipids and free fatty acids on myocardium are important pathogenetic mechanisms of cardiac remodelling and cardiac functional changes in obesity. Better understanding of these mechanisms could lead to the development of pharmacological methods of metabolic normalisation and inhibition of cardiac lipotoxic effects, in order to prevent chronic heart failure and other cardiovascular events in obese patients.

There are complex multifactorial associations between depression, coronary heart disease (CHD), and erectile dysfunction (ED). Depression is considered as an independent risk factor of CHD, as well as a strong predictor of higher risk of mortality and complications in CHD patients. The reported prevalence of ED among CHD patients ranges from 44% to 75%. In most cases of structural ED, a psychological component is also present. The manifestations of the cause-effect relationship between ED and depression could vary: ED might be a symptom of depression, while depression could also be caused by ED, and the improvement in erectile function can reduce the severity of depressive symptoms. CHD, depression, and ED have common risk factors, such as age, arterial hypertension, diabetes mellitus, dyslipidemia, obesity, low physical activity,
and smoking. Moreover, these diseases often coexist. Therefore, cardiovascular disease, ED, and depression belong to the same pathophysiological pathway and affect the clinical course of each other.

In patients with coronary heart disease (CHD), ischemic preconditioning facilitates the mechanisms of cardioprotection and metabolic adaptation to non-fatal ischemia, which is particularly important for the individuals with reduced coronary flow reserve. Development of new cardiac rehabilitation programmes, based on the phenomenon of ischemic preconditioning, is a promising non-pharmacological method of CHD management.