Aim. To evaluate the role of calculated glomerular filtration rate (GFR), microalbuminuria (MAU) and cystatin С assessment in renal pathology diagnostics among patients with arterial hypertension (AH) and normal or mildly elevated serum creatinine level.

Material and methods. In 114 non-diabetic patients with non-treated AH (age 53,0+1,0 years, creatinine 94,3+1,7 mkmol/1) and 158 patients with AH and diabetes mellitus, DM (age 56,2+0,7 years, creatinine 81,6+1,2 mkmol/1), serum creatinine, MAU by albumin/urine creatinine ratio, and calculated GFR by Cockroft-Gault and MDRD formulas (GFRl, GFR2) were assessed. In patients with AH and DM, cystatin С level was also measured.

Results. Among non-diabetic AH patients with normal creatinine level, decreased GFR2<60 ml/min/1,73 m2 but no GFRl reduction <60 ml/min/1,73 m2 was observed in 18,8%. MAU was registered in 7 non-diabetic AH patients (6,1%); in one participant, MAU was combined with decreased GFR2<60 ml/min/1,73 m2. Based on serum creatinine, MAU and GFR2 or GFRl measurement, subclinical renal pathology was diagnosed in 42,1% or 21,9% non-diabetic AH participants, respectively. Among subjects with AH and DM, MAU was observed in 12 (7,6%); in all patients with MAU creatinine level was normal; in 2 patients GFR2 was reduced <60 ml/mini,73 m2. In AH + DM group, cystatin С level was inversely related to GFR2 (r=-0,72; p<0,001), but not to GFRl.

Conclusion. Combined measurement of serum creatinine, MAU and GFR levels improves the diagnostics of subclinical renal pathology in AH patients. In patients with AH and DM, cystatin С is sensitive to early renal dysfunction.

Aim. To study the associations between 24-hour blood pressure monitoring (BPM) results and selected cardiovascular risk factors in young people.

Material and methods. In total, 204 students of Stavropol State Medical Academy were examined - 80 men and 124 women (mean age 20,3+0,32 years). Questionnaire survey focused on family history, health behaviours, psychological problems, and self-evaluated health. Anthropometry parameters, blood pressure, BP levels (measured by office and 24-hour BPM methods), and lipid profile were also assessed. According to the number of cardiovascular risk factors (CVD RF) diagnosed, all participants were divided into three groups: Group I - no CVD RF; Group II - one CVD RF; Group III - 2 or more VD RF.

Results. No CVD RF were observed in 25% of the participants. Most subjects had one CVD RF (34% males, 59,7% females), two CVD RF (32% and 11,7%), or three and more CVD RF (5,2% and 1,3%, respectively). Increase in CVD RF number was associated with elevated mean circadian levels of systolic (SBP), diastolic (DBP), mean (mBP) and pulse BP (PBP).

Conclusion. In young men and women, an association between CVD RF number and circadian BP levels was observed. Specifically, increased CVD RF number was linked to elevated mean circadian, mean daytime and mean nighttime SBP, DBP, mBP, and PBP.

Aim. To investigate CYP 3A4 system functioning and its clinico-laboratory correlations in acute myocardial infarction (AMI).

Material and methods. The study included 50 patients hospitalized in the first 24 hours of AMI with ST segment elevation (STE-AMI). Monoethylglycinexylidide (MEGX) test was performed at the hospital admission, at Day 4-5 and Day 14.

Results. Baseline MEGX level was significantly higher in non-complicated AMI group (132,1+16,85 ng/ml) than in patients with heart failure (HF) symptoms (31,9+2,02 ng/ml; p<0,001) or healthy volunteers (63,6+14,01 ng/ ml; p<0,001). Phenobarbital administration significantly enhanced CYP 3A4 activity in both AMI groups.

Conclusion. In AMI, CYP 3A4 system activity was suppressed among patients with acute HF symptoms. This could be explained by ischemic and congestive liver disturbances. In STE-AMI, pharmacological CYP 3A4 stimulation is possible.

Aim. To compare clinical and cost-effectiveness of ACE inhibitors in patients with arterial hypertension (AH) and coronary heart disease (CHD), aiming to guide the appropriate medication selection process.

Material and methods. The study included 60 patients, receiving standard combined pharmaceutical treatment, plus perindopril, or moexipril, or fosinopril (n=20 in each group). At Day 7, all patients were administered ramipril.

Results. Clinical effectiveness of fosinopril, moexipril, perindopril and ramipril was similar: in all groups, significant blood pressure reduction was achieved by Day 6 and sustained till Day 38 of ramipril therapy. All ACE inhibitors were well-tolerated. Maximal cost-effectiveness ("minimal cost" method) was observed for ramipril.

Conclusion. Assessing clinical and cost-effectiveness of various medications from one pharmacological group could be used for developing pharmaceutical therapy standards aimed to guide the medication selection process in individual patients.

Aim. To assess effectiveness and safety of a selective beta-blocker bisoprolol in patients with chronic heart failure (CHF) and Type 2 diabetes mellitus (DM-2).

Material and methods. In total, 81 patients with mild to moderate CHF, NYHA Functional Class (FC) II-III, left ventricular ejection fraction (FV EF) <45 %, and DM-2 were examined. Bisoprolol group included 49 individuals (60 %), control group - 15 (18 %). Total length of therapy and follow-up was 12 months. Control examination was performed at baseline, after 6 months of the treatment, and at the end of the study. The examination included clinico-functional assessment of general status, renal function, neuro-hormonal profile, circadian heart rate variability, and carbohydrate metabolism (glycated hemoglobin level, standard breakfast test with fasting and 2- hour postprandial measurements of plasma glucose, insulin and C-peptide levels).

Results. Bisoprolol substantially improved CHF FC, physical stress tolerability and LV EF, reducing heart rate and LV end-systolic volume, comparing to controls. Bisoprolol therapy did not affect DM-2 clinical course and did not result in insulin resistance progression or a need for more aggressive glucose-lowering therapy even among patients with clinically manifested CHF.

Conclusion. Due to its demonstrated effectiveness and safety, bisoprolol could be recommended as a part of complex therapy in CHF and DM-2 patients.

Aim. To study renal function and prognostic value of creatinine and glomerular filtration rate (GFR) levels in regard to lethality among patients with acute decompensation of chronic heart failure (AD CHF).

Material and methods. Fhe study included 392 patients hospitalized with AD CHF symptoms (mean age 65,2+8,4 years; 263 (68%) males; CHF duration - 3,6 years). Serum creatinine concentration was measured daily up to Day 7 of hospitalization. Persistently elevated creatinine level by at least 26,5 mkmol/1 pointed to deteriorating renal function. GFR was calculated according to Cockroft-Gault formula. Echocardiography at admission was performed in all participants.

Results. Baseline renal dysfunction (GFR<90 ml/min/1,73 m2) was observed in 270 (69%) patients, hospitalized with AD CHF. Severe renal failure (RF) - GFR<30 ml/min/1,73 m2, was observed in 54 (20%) subjects, including 11 (4%) with terminal RF - GFR<15 ml/min/1,73 m2. Deterioration of renal function during hospitalization was registered in 120 (30,6%) patients, being linked mostly to CHF duration. In this group, 13 (10,8%) patients died - substantially more than in participants without progressing renal dysfunction (19 (7%) deaths).

Conclusion. In patients hospitalized with AD CHF, baseline GFR decrease was observed in 69%, including 20% with severe renal dysfunction (GFR<30 ml/min/1,73 m2). Renal dysfunction progression during hospitalization, registered in 30,6% of AD CHF patients, was linked to CHF duration and higher lethality.

Aim. To study the effects of carvedilol and metoprolol tartrate on endothelium mono-layer and remodeling of myocardium, large vessels and kidneys in patients with post-infarction chronic heart failure (CHF).

Material and methods. The study included 50 patients (33 males, 66 %) with stable post-infarction chronic heart failure (CHF), Functional Class (FC) II-III. Mean CHF duration was 5,22+0,67 years. In 41,7 % patients, FC II CHF was diagnosed, in 58,3 % - FC III CHF. Clinical examination was performed at baseline and after 4 months of beta-adrenoblocker therapy. Main group (n=25) was administered carvedilol, control group - metoprolol tar-trate(n=25). Daily dose was titrated gradually; in carvedilol group, itwas43,ll±l,84 mg/d, in metoprolol group - 128,75+8,63 mg/d. Myocardial structure and function were assessed by echocardiography (EchoCG), vessel wall structure - by measuring intima-media thickness in common carotid arteries (CCA IMT). Endothelium monolayer and kidney function were assessed by measuring microalbuminuria (MAU) level.

Results. Four-month carvedilol therapy was associated with a substantial decrease in MAU (-47,4 %) and CCA IMT (-10,6 %); in metoprolol group, these changes were not significant. EchoCG results demonstrated a significant left cardiac chamber reduction.

Conclusion. Carvedilol improved endothelial function, facilitated reverse remodeling of myocardium, vessel wall and kidneys. Therefore, carvedilol therapy might be recommended for target organ protection in CHF

Aim. To study the aetiology of chronic heart failure (CHF) in Chuvash Republic.

Material and methods. The study was a part of a multi-center epidemiological program (EPOCHE) determining the prevalence of arterial hypertension (AH) and CHF in non-organised population of European part of the Russian Federation. A random representative sample included 3090 people aged over 15 years. After the screening, 231 patients with clinically manifested CHF were selected and examined at a hospital.

Results. The leading aetiological CHF factor was AH (88,8%), especially in combination with coronary heart disease (CHD) (58%); isolated AH was registered in 30.8% of the participants. Only in 8 subjects (3,5%), isolated CHD was the leading CHF cause. Isolated AH, as an aetiological CHF factor, was more frequent in women than in men (33,9% vs. 22,2%). In men, isolated CHD resulted in CHF 4.4 times more often than in women..

Conclusion. High population prevalence of AH and CHD combination (88,8%) explained their substantial impact into CHF aetiology.

Aim. To investigate the prevalence of anemia and renal dysfunction combination among patients with severe chronic heart failure (CHF), as well as the effects of intravenous (i/v) iron therapy.

Material and methods. In total, 42 patients (mean age 69,3+1,2 years) with Functional Class III-IV stable CHF (NYHA classification) were examined. Glomerular filtration rate (GFR) was calculated based on creatinine concentration (MDRD formula). Anemia was diagnosed by WHO criteria: hemoglobin (Hb) level <130 g/1 in men and <120 g/1 in women. Eleven patients were administered Venofer for 24 weeks. At baseline and after the treatment course, 6-minute walk test (6mw) was performed.

Results. Anemia was diagnosed in 17 (40,5%) patients, including 13 with iron deficiency. Chronic renal failure (CRF; GFR< 60 ml/min) was observed in 64,7 % of the participants. Clinical and laboratory parameters were compared in patients with cardiorenal syndrome (GFR<60 ml/min) with or without anemia. Significant negative correlation was observed between Hb and creatinine levels (p=-0,02), with positive correlation between hematocrit (Ht) and GFR levels (p=0,044). Intravenous iron therapy was associated with a significant increase in Hb (from 128,2+14,4 to 139,0+17,4 g/1; p=0,03), Ht (from 38,4+3,5 to 41,3+5,06; p=0,03), and physical stress tolerance (PST), according to 6mw test results.

Conclusion. The combination of cardiac pathology, renal dysfunction and iron-deficient anemia was typical of patients with severe CHF. Iron therapy was associated with significant increase in Hb, Ht, and PST levels, without any severe adverse effects.

Aim. To investigate endothelium-regulating and antioxidant effects of trandolapril and verapamil SR combination (Tarka) in patients with arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD).

Material and methods. In total, 42 COPD and AH patients, aged 48-70 years, were examined. All participants received continuous basis COPD treatment and 16-week Tarka therapy. At baseline and at the end of the study, lung function, systemic inflammation, oxidative stress and antioxidant potential parameters were measured.

Results. All patients achieved office-measured target blood pressure (BP) levels. Bronchial conductivity increase was explained by therapy-associated improvement in pulmonary hemodynamics. The medication was safe and well-tolerated by patients with COPD and AH. Decrease in C-reactive protein levels, possibly explaining antiinflammatory medication effect, pointed to the suppression of endothelium-damaging influences. The treatment was also associated with decreased lipid peroxidation, reduced serum levels of acylhydroperoxides, and increased concentration and activity of antioxidant enzymes.

Conclusion. AH and COPD therapy should include antihypertensive agents with pleiotropic effects, specifi- cally, suppressing systemic inflammation, correcting endothelial function, and enhancing antioxidant potential. These characteristics could act as additional criteria of AH treatment effectiveness in patients with combined cardiovascular and respiratory pathology.

Aim. To study losartan effects, as monotherapy and in combination with hydrochlorothiazide (HCH) and magnetic laser therapy (МГТ), on 24-hour blood pressure (BPM) and quality of life (QoP) parameters in patients with mild to moderate arterial hypertension (AH).

Material and methods. Bighty-three men with mild to moderate AH were examined (mean age 51,4+5,6 years). At baseline and after 4 weeks of the treatment, 24-hour BPM and QoB parameters were measured in all participants.

Results. After 4 weeks of the treatment, improved BP circadian rhythm (CR) was observed in all participants, especially in combined therapy groups. In the group of losartan, HCH and МГТ second 24-hour BPM demonstrated normalized BP CR, decreased prevalence of night CR type (from 39% to 25%), and reduced morning BP surge. Bosartan monotherapy, despite its good antihypertensive effect, did not result in BP CR normalization. Synergistic impact of combined pharmaceutical therapy and МГТ was observed in regard to antihypertensive effect and treatment tolerability Maximal changes in various Qor domains were registered among patients with initially low scores (73%); among participants with initially high scores (27%), Qor did not change significantly.

Conclusion. Tosartan combination with HCH and МГТ was effective in AH patients, demonstrating not only good antihypertensive effect, but also Qor improvement.

Aim. To assess renal artery stenting (RAS) effectiveness and safety in patients with renovascular hypertension (RVH) duration over 10 years.

Material and methods. Seventy-eight patients were randomized into main (n=26) and placebo groups (n=52). Primary end-point was systolic blood pressure (SBP) level. Secondary end-points included: restenosis incidence; glomerular filtration rate (GFR); effective renal plasma flow (ERPF); creatinine level and microalbuminuria (MAU); quality of life (QoL); renal biopsy and immuno-hystochemical assay data; renal vessel calcification; cerebral metabolism level.

Results. RAS resulted in average BP decrease from 181/107 to 142/93 mm Hg; after 6 weeks, no patient achieved target BP levels. Restenosis at 12 months was observed in 17% of the patients from both groups; another RAS was needed in 8%. According to dynamic nephroscintigraphy results, GFR reduced by 5% (p<0,05), and ERPF - by 3% (p<0,05). Creatinine level decreased by 3% (p<0,01), and MAU - by 7% (p<0,05). Assessed by SF-36 questionnaire, QoL was normal in 14- 29% only.

Conclusion. RAS remains an ineffective method of RVH treatment, even though it prevents renal artery thrombosis and improves RVH control to some extent.

Due to low effectiveness of arterial hypertension (AH) monotherapy, recent debates have concentrated on evidence-based effectiveness and safety of combined AH therapy. To improve treatment compliance, reduce treatment costs, and increase therapy effectiveness, fixed-dose combined antihypertensive therapy is used more and more actively. One of such fixed-dose combinations, with proved effectiveness and safety, is Tarka medication, including trandolapril and verapamil. The article reviews the literature data demonstrating fixed-dose trandolapril+verapamil combination effects on blood pressure level and target organ damage in AH, renal failure, diabetes mellitus, and coronary heart disease.

 

The recently emerged concept of cardio-reno-metabolic continuum supports common pathogenesis, development and progression risk factors (RF) for renal dysfunction and cardiovascular disease (CVD), as well as the importance of renal dysfunction, from subclinical disturbances to terminal renal failure, for CVD outcomes. Fhe review summarizes the data on uric acid as a marker of renal dysfunction and CVD RF. Original results, obtained by the authors, are also presented.

Trimetazidine is proved to be a highly effective metabolic agent, compared to other drugs with the same action. Trimetazidine shifts cardiac energy metabolism from fatty acid oxidation towards glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl-coenzyme A thiolase. In a number of randomized controlled trials, trimetazidine was shown to improve the ergometric exercise capacity and total workload, to reduce angina attacks and nitroglycerin total dose in patients with coronary heart disease, heart failure, and after coronary artery bypass graft surgery. It is especially important that trimetazidine is highly effective in diabetes-associated cardiac pathology. Clinical effectiveness of other metabolic agents is also discussed, and directions for further research are presented, based on evidence-based data analysis.