[Effectiveness and safety of losartan and its combination with amlodipine in therapy of arterial hypertension].

AIM: To estimate effectiveness and safety of losartan and its combination with amlodipine in therapy of arterial hypertension. MATERIALS AND METHODS: The study based at 6 clinical centres was conducted in two stages. All 160 patients with grade I-II AH (103 women and 57 men aged 54 ± 12 yr) participated in stage 1 of the study and patients of centre No 1 (n = 100) in stage 2. Losartan was used at a dose of 50-100 mg/24 h for 8 weeks (stage 1) and thereafter from week 9 to 26 (stage 2) in combination with amlodipine (5-10 mg/24 hr) if the desired AP level (< 140/90 mmHg) was not achieved. The following parameters were measured: systolic and diastolic AP (SAP and DAP) (office measurement and 24-hr monitoring), pulse wave propagation rate (PWPR), left ventricle mass index (LVMI), thickness of intima-media complex (IMT), blood biochemistry, tolerability of therapy and its side effects. RESULTS: Losartan alone decreased SAP and DAP from 150 ± 11/91 ± 7 to 132 ± 12/81 ± 8 mm Hg (office measurement) and from 144 ± 10/86 ± 9 to 128 ± 12/76 ± 10 mm Hg (24-hr monitoring); heart rate decreased fom 74 ± 8 to 70 ± 8/min (p < 0.05). SAP and DAP in 66 patients who completed stage 2 was 122 ± 6/73 ± 6 mm Hg or significantly lower than before therapy (147 ± 9/87 ± 9) (p < 0.001). Mean daily decrease of SAP and DAP according to 24-hr monitoring decreased from 144 ± 10 to 128 ± 12 and from 86 ± 9 to 76 ± 10 mm Hg respectively (p < 0.001). The target AP value was reached in 73% of the cases (99 out of 136 patients) after stage 1 and in 95% cases (63 out of 66) after stage 2. The values of LVMI (105 ± 23 and 98 ± 26 g/m2), PWPR from 16 ± 2.1 to 13 ± 3.5 m/s (p < 0.05), IMT (0.76 ± 0.16 and 0.80 ± 42 mm), and microalbuminuria (11.0 ± 1.7 and 8.6 ± 0.7 mg/24 hr) before and after completion of stage 2 were not significantly different in 66 patients (p > 0.05). Biochemical parameters of blood did not appreciably change. The safety profiles of both drugs were on the whole positive. Deaths and adverse reactions were absent barring clinically insignificant side effects in 28 of the 160 patients (17.5%). CONCLUSION: Losartan and amlodipine are effective and safe agents for AH therapy.

[Hormonal regulation of lipoprotein metabolism: the role in pathogenesis of coronary heart disease].

The character and role of hormonal dysregulation of lipoprotein metabolism during postprandial hyperlipemia were studied in patients with coronary heart disease (CHD) and hyperthyroidism as compared with healthy subjects. Pronounced hypertriglyceridemia alongside with the decreased high density lipoprotein cholesterol (HDL C) after standard fat load were associated with increased level of insulin and decreased level of cortisol. Moreover, in CHD patients fasting hyperinsulinemia becoming even stronger postprandially resulted in prevalence of antilipolytic action of insulin over lipid-mobilizing effect of cortisol; and an extended postprandial hypertriglyceridemia took place. Patients with hyperthyroidism and low cholesterol level both in atherogenic LDL and antiatherogenic HDL, demonstrated decreased level of apo AI (as in CHD patients) and apo B (three times lower than in CHD patients). Very low ratio of apo B/AI in patients with hyperthyroidism both in fasting and postprandial state was a clear indication of their lipoprotein profile antiatherogeneity. Thus, in patients with hyperthyroidism despite of low HDL C and apo AI levels, antiatherogenic properties of lipoprotein profile are probably determined by very low apo B/AI ratio induced by thyroid hormones, and might be explained by the influence of thyroid hormones on the expression of genes coding these apoproteins.

[Small dense low density lipoprotein particles: mechanisms of formation, atherogenic properties, possibilities of modification of their content in blood plasma].

Atherogenic low density lipoproteins (LDL) consist of subfractions of particles with different dimensions, density, proportion of various lipid components, affinity to apo B/E receptors, susceptibility to oxidation, and other properties. As a rule spectrum of LDL particles has one predominant central peak and several (up to 6) additional peaks containing particles which are smaller or larger than particles of the main peak. There are also smaller and bigger particles within the main peak itself. In normolipidemia average diameter of particles of the predominant main peak exceeds 25.5 hm (profile A), in combined hyperlipidemia main peak consists of smaller (<25.5 hm) particles (profile B). It has been shown in many studies that because of several characteristics (lower affinity to apo B/E receptors, prolonged presence in blood stream, susceptibility to oxidation and uncontrolled entrapment by macrophages) small dense LDL particles play significant role in atherogenesis. The authors of this review have demonstrated that in subjects with abdominal obesity and concomitant metabolic risk factors in postprandial period after standard meal LDL spectrum shifts towards small particles and this shift persists during 6 hours after meal. An apparently atherogenic subfraction of large cholesterol ester loaded particles is also described in this paper.

[Lowering of antiatherogenic significance of high density lipoproteins in obese persons]. / Snizhenie antiaterogennoi znachimosti lipoproteidov vysokoi plotnosti u lits s ozhireniem.

Protein and lipid components of blood serum high density lipoproteins (HDL) responsible for their functional activity were studied before and after fat load in subjects with normal body mass and various types of obesity. Subjects with abdominal obesity compared with those with gluteo-femoral obesity and normal body mass initially had pronounced disturbances in components of HDL and their acceptor capacity. Fat load caused changes of HDL composition in all study groups. Postprandial effect in persons with normal body mass became obvious 6 hours after load while in those with excess mass it occurred earlier - 3 hours after fatty meal. In subjects with gluteo-femoral obesity this effect remained on the same level while in those with abdominal obesity it became more pronounced by hour 6. Contrary to subjects with normal body mass and gluteo-femoral obesity fat load induced changes of HDL components in persons with abdominal obesity were not associated with augmented acceptor capacity of HDL what could be considered as proatherogenic effect.

Low-density lipoprotein subfractions during abdominal and gluteofemoral obesity.

Subfractional spectrum of plasma low-density lipoproteins in people with normal body weight and patient with obesity was studied by gradient electrophoresis (3-12%) in polyacrylamide gel. Low-density lipoprotein subfractions in fasting patients with abdominal and gluteofemoral obesity were primarily presented by small particles (compared to people with normal body weight). The composition of low-density lipoprotein subfractions underwent most pronounced changes in patients with abdominal obesity after single fat load.

Development of a model system for evaluation of human endothelial cell proliferation in vitro: possible clinical applications.

A system for evaluation of the ability of human blood serum to affect endothelial cell proliferation was developed and tested. The system based on incorporation of (3)H-thymidine into DNA was used to analyze the effects of hormone replacement therapy on endothelial repair and angiogenesis. Blood serum from 12 menopausal women less effectively activated endothelial proliferation compared to control donor serum. After 6-month hormone replacement therapy with Divina (a combination of estradiol and medroxyprogesterone), this index increased in seven female subjects (58.3%), but remained below the control level. The model proposed by us can be used in clinical practice and drug testing for evaluation of the influence of blood serum on vascular endothelium.

[Functional state of the vascular wall in patients with coronary arteriosclerosis and different types of reactions to psycho- emotional stress]. / Funktsional'noe sostoianie stenki sosudov u bol'nykh koronarnym aterosklerozom s razlichnymi tipami reagirovaniia na psikho- emotsional'nuiu nagruzku.

With changes in psychoemotional stress, antithrombogenic properties of the vascular wall and hemostatic parameters were evaluated in 25 healthy subjects and 46 patients with coronary heart disease (CHD) who differently performed a leader function when intrapersonal interaction was simulated by using a bioengineering "Gomeostat" device. There was a significant increase in the functional activity of the hemostatic system involving enhanced platelet functional activity and diminished blood procoagulative fibrinolytic activity and decreased antithrombogenic activity of the vascular wall in patients with CHD who showed a managerial tactics during simulated intrapersonal interaction in a minor group as compared to a group of followers among CHD patients.