EPIDEMIOLOGY AND PREVENTION
Aim. To present the results of the complex assessment of the associations between arterial wall structure and metabolic, infectious, and immune parameters in people free from cardiovascular risk factors (RFs). Material and methods. Among 400 examined healthy participants, aged 18-65 years, 25 did not have any cardiovascular RFs. Vascular ultrasound, with intima-media thickness (IMT) measurement, was performed using ALOKA 5000 device. Laboratory parameters included lipid profile, glucose, plasma C-reactive protein (CRP), pro-inflammatory cytokines, and specific IgG antibodies to CMV, HCV-1, Cl. pneumoniae, H. рylori, and β-streptococcus. Immune status was assessed by innate and acquired immune parameters. Results. A strong association between IMT and viral infectious factors (CMV and HCV-1) was observed. The interaction between infectious factors and arterial wall also involves blood lipids (triglycerides, low- and highdensity lipoprotein cholesterol, total cholesterol) and innate and acquired immune factors. Immune factors regulate vascular wall hemostasis, possibly controlling viral replication and preventing vascular inflammation. This hypothesis is confirmed by low levels of CRP and pro-inflammatory cytokines, as well as by no association between arterial wall thickness and inflammation markers. Conclusion. In healthy subjects without RFs, vascular wall is interacting with viral infectious factors, innate and acquired immune parameters, blood lipids and glucose. All these interactions are balanced and, therefore, do not result in intravascular inflammation.
Aim. To study the role of arterial hypertension (AH) and age at radiation exposure as potential risk factors of stroke (S) in Chernobyl “liquidators”. Material and methods. In total, 109 patients with S in late post-radiation period were examined. By the age at radiation exposure, all participants were divided into 4 groups: Group I (n=5) – under 20 years; Group II (n=61) – 20-29 years; Group III (n=37) – 30-39 years; and Group IV (n=6) – 40-49 years. In each age group, the dynamics of AH and S development was investigated. Results. In patients with AH, comparing to their peers with normal blood pressure, S developed more often, typically in the second decade after the radiation exposure, as a single-episode ischemic event, with neurological symptoms regressing within 24 hours. Maximal S risk was observed in Group II. The risk of haemorrhagic S was highest in Group III patients with AH. Age at radiation exposure was significantly associated with S type, severity, and number. Conclusion. In Chernobyl “liquidators”, AH was linked to increased S incidence. Younger age at radiation exposure was associated with higher risk of developing acute cerebrovascular events earlier in life.
ARTERIAL HYPERTENSION
Background: Experimental studies revealed pro-inflammatory properties of angiotensin II. We evaluated antiinflammatory effects of the angiotensin II subtype 1 receptor antagonist olmesartan medoxomil alone and in cotherapy with the HMG-CoA reductase inhibitor pravastatin, in patients with essential hypertension and microinflammation. Methods and results: We measured a panel of vascular inflammation markers, including high-sensitivity C-reactive protein (hsCRP), and lipid levels during 12 weeks of therapy with olmesartan (n=100) or placebo (n=99) in a prospective double-blind multicenter study. Pravastatin was added to the double-blind therapy at week 6 in both treatment arms. Blood pressure (BP) control was achieved with addition of hydrochlorothiazide. Olmesartan treatment had already significantly reduced serum levels of hsCRP (-15,1%; p<0,05), high-sensitivity tumor necrosis factor-alpha, hsTNF-alpha (-8,9%; p<0,02), interleukin-6, IL-6 (-14,0%; p<0,05), and monocyte chemotactic protein-1, MCP-1 (-6,5%; p<0,01) after 6 weeks of therapy, whereas placebo treatment (ie, BP reduction) had no major effect on inflammation markers. After 12 weeks of therapy, hsCRP (-21,1%; p<0,02), hsTNF-alpha (-13,6%; p<0,01), and IL-6 (-18,0%; p<0,01) decreased further with olmesartan and pravastatin co-therapy, but treatment with pravastatin alone (ie, co-therapy with placebo) did not significantly alter inflammation markers. In contrast, addition of pravastatin led to a significant (p<0,001) reduction in LDL cholesterol serum concentrations in the olmesartan and placebo treatment groups (-15,1% and -12,1%, respectively). Conclusions: Angiotensin II receptor blockade significantly reduces vascular microinflammation in patients with essential hypertension by as early as week 6 of therapy. This anti-inflammatory action of angiotensin II receptor antagonists may contribute to their beneficial cardiovascular effects.
Aim. To compare the effects of two beta-adrenoblockers (BAB) – a generic carvedilol and metoprolol tartrate – on lipid profile, carbohydrate and purine metabolism parameters in patients with arterial hypertension (AH) and overweight or obesity (OW/O). Material and methods. The study included 320 patients, receiving carvedilol (n=160) or metoprolol tartrate (n=160) for 24 weeks. The effectiveness of antihypertensive therapy (AHT) was assessed by blood pressure (BP) dynamics at each visit and at the end of the study, comparing to baseline BP levels. Safety parameters included adverse event (AE) profile and biochemical parameter dynamics (lipid profile, glucose, creatinine (Cr), uric acid (UA), potassium (К+) and sodium (Na+)). Results. As early as at the first visits, a significant reduction in baseline levels of systolic and diastolic BP (SBP, DBP) was observed (р<0,0001). Both carvedilol and metoprolol therapy resulted in a significant reduction of heart rate (HR) and body mass index, BMI (by 0,39±0,07 kg/m2 (р<0,0001) at the end of the study). Carvedilol therapy was associated with improved lipid profile and glycemia parameters, while metoprolol was metabolically neutral. One of the new, positive findings was the absence of adverse effects of carvedilol-based AHT on purine metabolism. Conclusion. In patients with Stage 1-2 AH and OW/O, a good antihypertensive effect was observed for both medications studied. The latter, due to its additional vasodilating effect, demonstrated beneficial effects on AH-associated metabolic parameters. Therefore, carvedilol should be a BAB of choice in patients with AH and metabolic risk factors.
Aim. To compare the effects of two therapeutic complexes (valsartan or losartan in combination with pioglitazone and non-pharmaceutical intervention) on vascular wall function in patients with arterial hypertension (AH), metabolic syndrome (MS), and recent ocular vessel occlusion. Material and methods. In total, the study included 47 patients (20 men, 27 women) with Stage 1-2 AH, Risk 4 (2008 DAH criteria). Mean age of the participants was 47,9±1,7 years. The age-matched control group included 25 healthy volunteers. Lipid profile, plasma lipid peroxidation, and vascular hemostasis parameters were assessed. To control blood pressure (BP) levels, 24 patients were administered valsartan (160 mg once a day), and 23 received losartan (100 mg once a day). Аll patients received pioglitazone (30 mg once a day) and non-pharmaceutical intervention. Results. The four-month complex therapy with valsartan normalised vascular wall function in AH patients with MS and ocular vessel occlusion. The complex therapy with losartan improved, but not normalized vascular wall function. The subsequent poor compliance with non-pharmaceutical therapy, even with continuing pharmaceutical treatment, reduced the beneficial effect of the complex therapy, which could be explained by persisting thrombosis risk in this clinical group. Conclusion. The complex intervention was more effective in combination with valsartan, and less effective in combination with losartan, in improving vascular hemostasis.
Aim. Microalbuminuria (MAU) and hypertension (AH) are risk factors (RFs) for diabetic nephropathy in patients with Type 2 diabetes mellitus (DM-2). Recent data suggest that blockade of the renin-angiotensin system (RAS) slows the progression of diabetic nephropathy. In contrast, the results on the renoprotective effect of calcium channel antagonists (CAs) are conflicting. We evaluated the effectiveness of lercanidipine, in comparison with ramipril, on the reduction in albumin excretion rate (AER) and blood pressure (BP) in mild-to-moderate hypertensive patients with DM-2 and persistent MAU. Material and methods. A total of 277 patients were enrolled in a multi-centre, randomised, double-blind, activecontrolled, parallel-group trial: 180 were randomised to receive 10-20 mg/d of lercanidipine or 5-10 mg/d of ramipril and followed up for 9-12 months. The primary outcome was the change in AER from baseline. Results. After 9-12 months of follow-up, a reduction in AER of -17,4±65 μg/min (р<0,05) and -19,7±52,5 μg/ min (р<0,05), in the lercanidipine and ramipril group, respectively, was observed, without significant differences between the groups. A significant reduction in systolic and diastolic BP was observed in both the lercanidipine and ramipril-based treatment groups (р<0,0001 for both). Conclusion. Treatment with lercanidipine (10-20 mg/d) does not worsen albuminuria in patients with AH, DM-2, and MAU. Both lercanidipine and ramipril treatments resulted in a significant reduction in AER, without a statistically significant difference between the two groups.
ARRHYTHMIAS
Aim. To assess the effectiveness of depressive disorder (DD) treatment with fluvoxamine in patients with various forms of atrial fibrillation (AF), as well as to investigate fluvoxamine effects on AF clinical course. Material and methods. Group I included 51 patients with various forms of AF and DD, receiving fluvoxamine (50 mg once a day) for 6 months. Group II included 49 patients with AF and non-treated DD (comparison group). All participants received standard antiarrythmic therapy. At 6 months, the incidence of AF attacks and transition from tachycardic to normocardic AF, blood levels of fibrinogen, and depression severity (CES-D questionnaire) were assessed. Results. Three AF patients were withdrawn from fluvoxamine therapy at Week 1, due to adverse effects. In the other Group I patients (n=48), fluvoxamine reduced DD severity by 2,8 points on average (p<0,01). Fluvoxamine treatment was also associated with reduced AF attack incidence in 48,3±9,3 % of the patients with paroxysmal and persistent AF (p<0,01), and transition from tachycardic to normocardic AF in 47,4±11,5 % of the patients with permanent AF (p<0,05). The beneficial clinical effect (reduced DD severity, decreased AF attack incidence, reduced fibrinogen levels) was maximal in patients with paroxysmal and persistent AF, and minimal in patients with permanent AF, possibly due to more advanced heart failure and more severe clinical course of the disease. Conclusion. An antidepressant fluvoxamine reduces DD severity in AF patients and improves the clinical course of various AF forms.
Aim. To study clinical effectiveness and safety of propafenone and amiodarone in patients with arterial hypertension (AH), coronary heart disease (CHD), chronic heart failure (CHF) with preserved left ventricular (LV) systolic function, and atrial fibrillation (AF). Material and methods. The study included 110 34-66-year-old patients from various Russian regions, with paroxysmal and/or persistent AF. To prevent AF episodes, the participants were administered propafenone (n=59) or amiodarone (n=51) for 12 months. Results. The treatment of the leading pathology resulted in achieving target blood pressure levels (in 67,3 % of the patients), as well as in reducing functional class of angina (70 %) and CHF (94,5 %). In its turn, this resulted in reduced incidence (-72,9 %) of hospitalisations due to CHF decompensation. After 12 months of the treatment, propafenone effectiveness was 54,2 % — similar to that for amiodarone (52,9 %). In 33,9 % of the patients taking propafenone, the number of AF episodes was reduced by 86,6 %, their total duration — by 70,1 %, ventricular rate during the paroxysm — by 43,1 %, while the number of asymptomatic episodes increased by 30,9 %. Propafenone was also safer than amiodarone: the respective incidence of adverse effects was 0 % vs. 31,6 %. Conclusion. Propafenone, a Class IC antiarrythmic medication, was characterised by high antiarrythmic effectiveness and safety, and could also be combined with beta-adrenoblockers in CHF patients with preserved LV systolic function, AH, CHD, and paroxysmal and/or persistent AF.
HEART FAILURE
Aim. To assess the effects of taurine on the parameters of 24-hour blood pressure monitoring (BPM) in patients with metabolic syndrome (MS) and chronic heart failure (CHF). Material and methods. In total, 60 patients were examined (mean age 54,4±7,4 years). The control group (CG) received enalapril and indapamide. The main group (MG) was additionally administered taurine for 12 months. All participants underwent anthropometry, office BP measurement, 24-hour BPM, and lipid profile assessment at baseline and at the end of the study. Results. The treatment was associated with changes in circadian profiles of systolic and diastolic BP (SBP, DBP) in both groups, with greater positive dynamics in the MG. The number of the patients with а “dipper” BP curve increased. Mean BP levels were significantly reduced. In the MG, time index for mean 24-hour SBP and DBP significantly decreased, by 49,9% and 42,3%, respectively. Mean 24-hour, day-time and night-time variability of SBP and DBP was normalised in the MG. Conclusion. Adding a metabolic agent to the combined antihypertensive therapy facilitated effective correction of circadian BP disturbances.
METABOLIC SYNDROME AND DIABETES MELLITUS
Aim. To investigate the role of obesity (O), as a psychopathological disorder, in metabolic syndrome (MS) development; to assess the effectiveness of psychotherapeutist’s participation in MS prevention and treatment. Material and methods. The presence and stage of O was assessed by body mass index (BMI). The study included 3 groups: Group I – patients with bulimia nervosa and O (n=64), including individuals with cardiovascular disease, CVD (n=12); Group II – patients with CVD, but without O or psychopathology (n=28); Group III – patients with CVD and with or without O, MS, and diabetes mellitus, DM (n=78). Group III was divided into 4 subgroups by symptom severity. In Groups I and II, psychological profile was assessed by clinical interview and MMPI test; in Group III, all MS components were measured, including lipid and glucose metabolism parameters. Results. In Groups I and II, CVD patients, regardless of concomitant O, had similar MMPI profiles, with maximal scores for scale 1 (hypochondria), which was different from the profile of bulimic patients in Group I. In Group II, in contrast to Group I and CVD subgroup, a tendency towards weight reduction in more advanced age was observed. The same tendency was also observed in 3 subgroups of Group III, being the strongest in the subgroup with the most severe symptoms (MS and DM). In all 4 subgroups of Group III O as a specific MS component, preceding the other MS symptoms, but independent from them in the case of developed MS. Conclusion. The only effective method for MS prevention is psychotherapeutic diagnostics and treatment of O at the stage preceding the development of metabolic disturbances. In the treatment of MS patients, the role of psychotherapeutist is complementary, being aimed at weight reduction by treating eating disorders.
OPINION ON A PROBLEM
The paper is focused on erectile dysfunction (ED) as an inter-disciplinary problem. The detailed analysis of relevant clinical trials and meta-analyses is performed, demonstrating a causal relationship between ED and coronary heart disease, arterial hypertension, dyslipidemias, and diabetes mellitus. The role of common cardiovascular (CVD) risk factors (RFs) in ED development, as well as a shared, endothelial dysfunction-related pathogenetic mechanism of CVD, is discussed. The prevalence of ED and androgen deficiency, together with their link to metabolic syndrome (MS), is presented. It is shown that ED could be regarded as CVD predictor, and that early diagnostics of the RFs common for CVD and ED can be used for risk prediction and identification of highrisk groups. Since metabolic RFs are common for CVD, ED, and androgen deficiency, further research in this area may facilitate more efficient approaches to prevention and treatment of these diseases.
Vascular wall infiltration with lipoproteins, in particular with low-density lipoprotein (LDL) cholesterol (LDLCH), plays an important role in atherosclerosis pathogenesis. Elevated LDL-CH levels are associated with increased risk of coronary heart disease (CHD). Based on the evidence from experimental and clinical studies, there is a direct link between LDL-CH reduction and decreased incidence of cardiovascular events. Statins are medications of choice for LDL-CH reduction; however, statin monotherapy does not always result in target LDLCH level achievement, due to pharmaco-genetic factors and adverse effects of the therapeutically effective statin doses. In these clinical situations, a combination of low-dose statins with other lipid-lowering agents is effective. Recently, high effectiveness of statin combination with ezetimibe (inhibitor of intestine CH absorption) has been demonstrated. It is explained by targeting both mechanisms which determine blood CH levels (intestine absorption and hepatic synthesis), with a substantial reduction in LDL-CH levels as a result.
The classification of angiotensin-converting enzyme (ACE) inhibitors is presented. The use of these medications in various clinical situations is discussed, including chronic heart failure, coronary heart disease, metabolic syndrome, diabetes mellitus, renal pathology, myocardial hypertrophy, proteinuria / microalbuminuria, and cerebrovascular disease. Drug interaction and tolerability aspects of ACE therapy are also discussed.
REVIEWS
The paper discusses modern aspects of epidemiology, pathogenesis, clinical course, diagnostics, and treatment of the patients with chronic heart failure (CHF) and intact left ventricular ejection fraction (LVEF). CHF with intact LVEF comprises over 50% of all CHF cases, and is more prevalent in elderly women. Its leading causes include arterial hypertension (AH) and diabetes mellitus (DM). Current diagnostic problems are related to over-estimated role of LVEF reduction, which reflects substantial myocardial damage not typical for AH and DM. The limitations of classical Doppler ultrasound in diastolic dysfunction (DD) diagnostics are discussed. The combination of classical and tissue Doppler ultrasound provides a more precise estimation of systolic and diastolic LV function. This method, in combination with natriuretic peptide level measurement, is the basis for the diagnostic algorithm of CHF with intact LVEF. A new hemodynamic concept of CHF development is presented. The key clinical trials on the treatment of CHF with intact LVEF are reviewed. In conclusion, the author discusses strengths and limitations of the two concepts of CHF with intact LVEF, as a separate disease or a phenotypical manifestation (stage) of “classical” systolic CHF.
Over the last few decades, vast evidence has emerged, confirming polygenic hereditary nature of arterial hypertension (AH). Reduced renal salt excretion, genetic or acquired due to diseases, ageing, obesity, or other factors, is a key mechanism in AH pathogenesis. AH development should be regarded as a compensatory reaction, aimed at increasing renal salt excretion, normalising circulating blood volume, and maintaining homeostasis.
Various clinical forms and complications of atherosclerosis remain the leading causes of morbidity and mortality in both developed and developing countries. HMG-CoA reductase inhibitors (statins) are the key components of pharmaceutical treatment in patients with dyslipidemia (DLP) and atherosclerosis. Statins have been thoroughly studied not only in randomised clinical trials with “hard” end-points, but also in the so called regression studies. The latter tested the hypothesis of qualitative and quantitative changes in coronary arteries (CA) due to aggressive reduction (-40-50% from baseline) of low-density lipoprotein (LDL) cholesterol levels. The results of the first regression studies justified the increase of statin doses in clinical practice, as well as led to large randomised clinical trials of statin therapy. In current regression studies, vascular atherosclerosis is monitored using such methods as intima-media thickness assessment, magnetic resonance imaging, and intravascular ultrasound. Reduced progression of carotid atherosclerosis (METEOR Study, rosuvastatin 40 mg/d; ENHANCE Study, ezetimibe 10 mg/d plus simvastatin 20 mg/d) and CA atherosclerosis (REVERSAL Study, atorvastatin 80 mg/d), as well as atherosclerosis regression (ASTEROID Study, rosuvastatin 40 mg/d), was demonstrated. Aggressive lipid-lowering effect (-40-50%), observed for high statin doses in modern regression clinical trials, was well-tolerated, with no severe adverse events. The results and principles of regression studies could be widely used in clinical practice, to optimise the treatment of severe DLP and atherosclerosis.
INFORMATION
ISSN 2619-0125 (Online)