[Comparative genetic analysis of different forms of low-renin arterial hypertension].

High level of clinical and genetic heterogeneity is a characteristic of arterial hypertension (AH) that is one of the most wide-spread cardiovascular diseases. In most cases (excluding a few monogenic forms), AH is a polygenic disease and genes of renin-angiotensin-aldosterone system play an important role in AH predisposition. 20-25% AH cases occur during low activity of renin in blood plasma (low-renin form of AH) while aldosterone production can be increased (hyperaldosteronism, HA) or normal. We examined polymorphism of genes that code the renin-angiotensin-aldosterone system components in the groups of low-renin forms of AH, namely, primary HA, idiopathic HA and AH with normal level of aldosterone. For all HA cases, the absence of chimeric CYP11B2/CYP11B1 gene that is a cause for monogenic disease--amilial HA of first type, was shown. A comparison of distributions of alleles and genotypes of polymorphous regions of genes: CYP11B2 (C-344T), REN (C-5434T, C-5312T and A BglI G), AGT (Thr174Met), ACE (I/D), CMA (G-1903A), AT2R1 (A1166C) and of their combinations is the groups described above was done. The analysis of carriership of the alleles and genotypes combinations of the polymorphous regions has shown that genes CYP11B2, REN, ACE, CMA andA T2R1 participate in development of low-renin HA. The results are evidence of similarities and some definite differences in genetic nature of the different forms of low-renin AH and, to say more widely, argue that the investigation of genetic predisposition for clinically heterogeneous forms of polygene diseases by comparison of groups of patients, separated in accordance with peculiarities of disease course, holds much promise for their hereditary background understanding.

[Contribution of CYP11B2, REN and AGT genes in genetic predisposition to arterial hypertension associated with hyperaldosteronism].

We carried out comparison of distribution of alleles and genotypes of polymorphic loci of renin-angiotensin-aldosterone system genes: CYP11B2 (C-344T), AGT (Thr174Met) and REN (C-5434T, C-5312T, and A BglI G) and their combinations in two groups of patients with low renin forms of arterial hypertension (AH). Group 1 included 59 patients with low renin hyperaldosteronism (HA) at the background of glomerular zone adenoma and hyperplasia of adrenal cortex. Group 2 included 28 patients with low renin hypertensive disease characterized by normal level of aldosterone. Complex analysis of carriership of allele and genotype combinations evidence for the difference in genetic nature of two forms of low renin AH. Participation of CYP11B2 and REN and possibly AGT genes in development of low renin AH was convincingly shown.

[Effect of strict glycemic control on clinical state and course of the disease in patients with chronic heart failure and type II diabetes mellitus. Results of the REMBO "rational effective multicomponent therapy in the struggle against diabetes mellitus in patients with congestive heart failure" study].

With the aim to investigate influence of glycemic control on clinical state and course of disease, renal function, and neurohormonal profile of patients with chronic heart failure (CHF) and type 2 diabetes mellitus (DM) we studied 81 patients with NYHA functional class (FC) II - III CHF, left ventricular ejection fraction (LVEF) 45% and type 2 DM. As a result of randomization 2 groups were formed - active with achievement of target levels of glycemia (n=41) and usual treatment (n=40). Retrospective analysis in dependence of efficacy of sugar lowering therapy was also conducted. Group 1 (n=18) comprised patients with achieved 1% lowering of glycated hemoglobin (HbA1 ), group 2 (n=26) - patients with bA1c lowering < 1%, group 3 (n=31) - patients with increase of HbA1 . Total duration of the investigation for the first analysis was 12, for the second - 6 months. Control examination was carried out at baseline, after 6 and 12 months of investigation and included assessment of clinico-functional status, glomerular filtration rate, neurohormonal profile (brain natriuretic peptide, noradrenalin, and angiotensin II). The state of carbohydrate metabolism was assessed with the help of determination of the level of HbA1c and oral glucose tolerance test. Absence of dynamics of glycemia in active and nonactive groups, in the active group improvement of clinico-functional status, quality of life, and parameters of remodeling was noted. Complementary retrospective analysis revealed improvement of functional status, renal function, and lowering of RAAS activity at 1% lowering of HbA1 and achievement of its target values. With this it was shown that betterment of functional possibilities ensued at lowering of HbA1c level not less than by 0.8%. Thus necessity and efficacy of strict glycemic control of DM in patients with CHF was proved.

[Efficacy and safety of the use of metformin in patients with chronic heart failure and type 2 diabetes mellitus. results of the study "rational effective mulicomponent therapy in the battle against diabetes mellitus in patients with chronic heart failure"].

Aim of the investigation was to study safety of therapy with metformin and its effect on clinical, hemodynamic, functional and neurohumoral status in patients with chronic heart failure and type 2 diabetes mellitus DM). Eighty one patients with light and moderate NYHA functional class (FC) II-III CHF, left ventricular ejection fraction < 45%, and DM were examined. As a result of randomization 2 groups were formed: with active (n=41) and usual (n=40) treatment. In active group with achievement of target levels of glycemia 24 (59%) patients were on oral hypoglicemic drags, 17 (41) patients received. All patients were on basal therapy of CHF. Initially efficacy and safety of metformin was investigated in a cohort of active treatment (jn metformin n=29, control n=12), including patients who were prescribed metformin not for the whole period. In addition in active group analysis was carried out among patients, who continually were treated with metformin for 12 months (n=30) in comparison with patients never treated with metformin (n=8). Total duration of the period of treatment and supervision was 12 months. Control examination was conducted before randomization, after 6 months of treatment, at the end of the study and included assessment of clunico-functional status of patients, renal function (GFR), neurohumoral profile (MNUP, NA, AII). The state of carbohydrate metabolism was assessed with the help of determination of HBA1C level and test with nutritional load given as of common breakfast -- 2-3 in the course of which fasting and postprandial level (in 2 hours after breakfast) of glucose (GLC), and fasting insulin and C-peptide. Overall safety of metformin was confirmed -- throughout whole period of follow up with different variants of comparative analysis no cases of lactic acidosis were revealed. Practical lack of positive influence of metformin on glycemia at its initially not high level was accompanied with improvement of FC CHF, parameters of central hemodynamics, augmentation of functional capacities of patients, improvement of quality of life, lowering of number of decompensations of CHF and diminishment of degree of activation of SAS. It can be suggested that this dynamics is conditioned by the presence of cardioprotective properties in metformin what allows to recommend its application in patients with CHF and type 2 DM.