Developing approaches to treating arterial hypertension in regard to possible pathways of angiotensin II synthesis

Aim. To study antihypertensive effects of AT1-receptor blocker eprosartan and ACE inhibitor enalapril, in regard to leading pathway of angiotensin II (AT II) synthesis among arterial hypertension (AH) patients with various functional status of renin-angiotensin-aldosterone system (RAAS). Material and methods. In total, 54 AH patients were examined. RAAS parameters and chymase activity were measured at rest and after orthostatic and captopril tests. Thirty-eight out of 54 patients were included into an open comparative cross-over two-group study, being administered eprosartan or enalapril. Antihypertensive effect was assessed after 8 weeks of treatment, by office blood pressure (BP) levels and 24-hour BP monitoring (BMP) results. Results. Basic criteria for identifying leading AT II synthesis pathway were proposed: antihypertensive reaction type in captopril test and baseline level of plasma chymase activity. Assessing eprosartan and enalapril treatment efficacy, it turned out that both agents had significant, similar antihypertensive effects, with eprosartan’s dominating influence on pulse BP. Eprosartan therapy was more effective in low-renin AH patients. Enalapril was less effective than eprosartan in patients with alternative, chymase-dependent pathway of AT II synthesis. Conclusion. Leading pathways of AT II synthesis in AH patients might be BP reduction in captopril test and baseline level of plasma chymase activity. Eprosartan therapy was more effective in low-renin and severe AH, that might be linked to its effects on alternative pathway of AT II synthesis

COMPARATIVE ANALYSIS OF LOSATAN AND ENALAPRIL ANTIHYPERTENSIVE EFFICACY (ELLA TRIAL)

Aim. To compare antihypertensive efficacy of АТ1 receptors blocker (losartan) and ACE inhibitor (enalapril), including their combinations with hydrochlorothiazide.Material and methods. 60 patients (30-65 y.o.) with arterial hypertension (HT) of stages 1-3 were involved in 12-week opened comparative randomized study. Patients of group-I (n=30) received losartan, patients of group-II (n=30) - enalapril. Blood pressure (BP) changes assessed on the basis of clinical measurements and ambulatory monitoring. Microalbuminuria (MAU) levels, plasma aldosterone levels and plasma renin activity were estimated.Results. Target BP levels were reached in 76,6% of patients in group-I and in 73,3% of patients in group-II. Among patients with moderate HT of stage 2 (n=50) target BP levels were reached in 96% of patients in group-I and in 72% of patients in group-II. Patients of both groups had positive changes in BP levels according to ambulatory BP monitoring. Significant reduction in MAU level and uric acid plasma concentrations were observed.Conclusion. Losartan (Losap, Zentiva) and losartan combination with hydrochlorothiazide (Losap-plus, Zentiva) demonstrated antihypertensive efficacy comparable with this of enalapril as well as nephroprotective features

Candesartan effectiveness in essential arterial hypertension and renal arterial hypertension

Aim. To study candesartan effectiveness and tolerability in essential arterial hypertension (ГАН) and AH associated with chronic renal disease.Material and methods. This 12-week open, controlled study included 14 patients (mean age 43,4±16 years) with diagnosed ГАН (n=9) or secondary AH of renal etiology (n=5). At baseline and after 12 weeks of candesartan therapy, office blood pressure (BP) measurement, 24-hour BP monitoring (BPM), vectorcardiography and decar-tography measurements of plasma renin activity, aldosterone, potassium levels and microalbuminuria (MAU) were performed.Results. Target BP level <140/90 mm Hg was achieved in 6 out of 14 patients (42,8 %). Additional hydrochlorothiazide (HCT) therapy increased antihypertensive effect of candesartan. On average, MAU reduced from 63,5±16,8 to 31,7±24,4 mg/d (p<0,0001).Conclusion. Candesartan therapy, especially combined with HCT, was effective in patients with mild to moderate AH, providing organo-protection. It could be recommended not only in ГАН, but also in symptomatic AH associated with chronic renal disease

Trandolapril and verapamil SR combination effectiveness in arterial hypertension patients

Aim. To study the effects of fixed4dose combined trandolapril and verapamil SR (Tarka) therapy on blood pressure (BP) and renin-angiotensin-aldosterone system (RAAS) patients with in essential arterial hypertension (EAH) and renal AH. Material and methods. The study included 20 patients with mild to moderate AH; 16 completed the study. EAH was diagnosed in 9 participants, secondary AH and chronic pyelonephritis – in 7. At baseline and 8 weeks later, office BP measurement, 24-hour BP monitoring (BPM), vectorcardiography and decartography parameters, renin activity (RA), aldosterone, potassium, microalbuminuria (MAU) level measurement were performed. Results. Target systolic BP (SBP) levels, <140 mm Hg, were achieved in 93,7%, and target diastolic BP (DBP) levels, <90 mm Hg – in 62,5% of the cases. Total target BP level achievement rate was 62,5%. According to 24-hour BPM data, positive day and nighttime SBP and DBP dynamics was observed. Mean MAU reduced significantly, from 27,6±23,9 mg/d to 17,2±14,5 mg/d. RASS status improved, as the number of patients with initially decreased RA halved. Conclusion. Antihypertensive effectiveness was demonstrated for Tarka medication in patients with mild to moderate AH. Its effectiveness was similar in participants with EAH and renal AH. Positive MAU dynamics confirms Tarka nephroprotective action

Myocardial functional status in patients with arterial hypertension and hyperaldosteronism: orthogonal electrocardiography assessment

Aim. To study orthogonal electrocardiography (ECG) parameters among arterial hypertension (AH) patients, in regard to renin-angiotensin-aldosterone system (RAAS) functional status. Material and methods. The study included 41 AH patients, mean age 45±2.8 years, and control group of 41 healthy individuals, mean age 41±7 years. Plasma aldosterone concentration (PAC) and plasma rennin activity (PRA) were measured at rest and after 4-hour walking. In all participants, 12-lead ECG and orthogonal ECG were registered, assessing left ventricular hypertrophy (LVH) criteria: Sokolow-Lyon criterion, Cornell index, Rx+Sz summary index, and repolarization acceleration vector module (G). Results were compared with echocardiography (EchCG) signs of LVH. Results. All patients had low-renin AH with various PAC levels. Three groups were identified: Group I (n=16), with adrenal cortex aldosteroma; Group II (n=12), with adrenal cortex hyperplasia; Group III (n=13), with normal PAC and no adrenal pathology. Comparing to Groups II and III, Group I had higher levels of systolic and diastolic blood pressure (BP), as well as more pronounced hyperaldosteronemia and hypokaliemia (p<0.05). Mean Cornell index in Group III was significantly lower than in Group I: 1.6±0.2 vs 2.5±0.2 mV, respectively. G index in Group III (71±9 ms) was significantly greater than in Groups I (35±5 ms) or II (47±6 ms). Inter-group differences for other parameters were not observed. Conclusion. Patients with adrenal cortex aldosteroma had significantly higher BP levels, more pronounced hyperaldosteronemia, hypokaliemia, and ECG signs of LVH, comparing to Groups II or III

Selective beta-blocker bisoprolol: effectiveness and safety in complex treatment of patients with chronic heart failure and Type 2 diabetes mellitus. RAMBO-DM CHF Study results

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