Vol 81, No 5 (2009)

The end of the XX century brought the discovery of the mechanism regulating cholesterol metabolism in humans and understanding of the cause of family hypercholesterolemia. Statins, introduced in early 1990es, failed to solve all the problems of atherosclerosis. Statins reduce blood cholesterol, but can also suppress activity of inflammation in the vascular wall, activity of peroxidation, can block proliferation of smooth muscular cells. The role of all these mechanisms should be carefully investigated as well as efficacy of innovative drugs.

Aim. To determine plasmic concentrations of NT-proBNP, TNFalpha and IL-6 in patients with coronary heart disease (CHD) complicated with chronic cardiac failure (CCF); to compare these parameters with hemodynamic and functional ones. Material and methods. A total of 157 CHD patients (84.1% males, mean age 54.3 ± 6.8 years) were divided into 3 groups matched by sex and age according to the presence of CCF and left ventricular (LV) or systolic dysfunction. Results. CCF patients with LV dysfunction or intact LV function had much higher plasmic concentrations of neurohumoral mediators than CHD patients without CCF. A plasmic NT-proBNP level over 1000 fmol/ml was associated with a 5.5-fold increase in the relative risk of LV diastolic dysfunction for CCF patients (rR 5.6; 95% CI 1.4-30.0; p = 0.0065) while an IL-6 level over 6.1 pg/ml was associated with a 9-fold increase in this risk (rR 8.9; 95% CI 2.3-35.4; p = 0.00001). Plasmic NT-proBNP and IL-6 levels went up in correlation with a CCF functional class. A plasmic level of TNFalpha correlated with anginal functional class. Conclusion. Changes in plasmic levels of the above neuromediators are associated with changes in some LV function and functional parameters of CCF patients.

Aim. To evaluate platelet activity changes in patients with coronary artery disease (CAD) treated with aspirin, clopidogrel and combination of these drugs; to estimate the rate of resistance of CAD patients to antiplatelet treatment. Material and methods. 199 patients with stable CAD were included in the study. Of them, 83 were given aspirin, 46 received clopidogrel, 34 - double antiplatelet therapy (both aspirin and clopidogrel). The trial also studied an additional group of 18 CAD patients on double antiplatelet therapy who had hemorrhages. The control group consisted of 25 healthy volunteers. Platelet aggregation was measured both by a mean size of aggregates (MSA) and light transmission (LTM, Born method) using BIOLA platelet aggregation analyzer. A platelet shape, leukocyte-platelet aggregates (LPA) and erythrocyte-platelet aggregates (EPA) in the whole blood were studied using scanning electron microscopy. The levels of IL-6 and sVCAM were also measured. Results. It was found that 59.8% patients with CAD had high platelet reactivity revealed in 94.9% of cases by measuring spontaneous and induced by 0.1 mcM ADP platelet aggregation. LTM revealed increased platelet reactivity only in 10.7% patients. Resistance to aspirin correlated with the presence of LTA (r = 0.629, p = 0.0001) and the number of large "reticulated" platelets (r = 0.334, p = 0.001). Low platelet reactivity was associated with the presence of circulating EPA (r = -0.362, p = 0.008). Administration of clopidogrel did not decrease platelet reactivity to normal levels in 34.7% patients which correlated with the presence of LPA and EPA. In 83.3% patients with hemorrhages platelet aggregation, induced by 5.0 mcM, ADP was dramatically decreased. Conclusion. Resistance to antiplatelet therapy is related to platelet heterogeneity, the presence of inflammation and state of erythrocytes. LT is capable to reveal only a part of patients resistant to antiplatelet drugs. To fully identify these patients, it is necessary to register spontaneous platelet aggregation and aggregation induced by low doses of ADP. Redundant inhibition of platelet reactivity could be the cause of hemorrhagic events.

Aim. To determine distribution of different atherosclerosis risk factors and their correlation with severity of coronary arteries (CA) affection in young men. Material and methods. A total of 235 males aged 28-45 years were examined with coronarography which detected more than 50% narrowing in one or several major CA in 200 patients (the study group with coronary artery disease), 35 males without coronary stenosis served control. Atherosclerosis risk factors, serum lipids, lipoprotein(a), fibrinogen, C-reactive protein (CRP) were assessed. Results. Smoking and hyperlipidemia (HLE) were registered in the study group more frequently. The level of lipoprotein(a) above 30 mg/dl was recorded in 98 (49%) and 7 (20%) patients of the study and control group, respectively (p = 0.001). As shown by a correlation analysis, the number of affected CA was associated with smoking (r = 0.2; p < 0.001), HLE (r = 0.23; p < 0.001), concentration of total cholesterol (r = 0.23; p < 0.0.001), lipoprotein (a) (r = 0.26; p < 0.001) and CRP (r = 0.26; p < 0.05). The level of lipoprotein(a) in patients with myocardial infarction and occluded artery was significantly higher than in patients without myocardial infarction and non-occlusive CA affection. Conclusion. The presence and severity of coronary atherosclerosis in young men with coronary artery disease are associated with smoking, HLE and high concentration of lipoprotein (a).

Aim. To investigate antihypertensive efficacy and safety of a fixed combination of ACE inhibitor enalapril with thiaside diuretic drug hydrochlorothiaside (HCT) in hypertensive patients with a high and very high risk of cardiovascular complications. Material and methods. The trial has covered 7796 hypertensive patients from 28 cities (42 clinics) of Russia, Ukraine, Belarus and Georgia. All the patients had a high and very high risk of cardiovascular complications. The protocol provides for measurements of clinical arterial pressure, 24-h monitoring of arterial pressure. Diabetic patients' plasma was examined for glucose concentrations. All the patients received enalapril in combination with HCT in doses from 10/6.25 to 40/25 mg/day for 3 months. Results. After 3 month treatment target systolic arterial pressure (SAP) was achieved in 81% patients, diastolic pressure (DAP) - in 88%, by SAP and DAP - 77%. By 24-h blood pressure monitoring, 24-h, diurnal and nocturnal blood pressure significantly decreased in 60 patients. Target 24-h blood pressure was achieved in 78% patients. Pressure load parameters lowered significantly for SAP and DAP for 24 hours, diurnal and nocturnal pressure. Glucose levels in patients with diabetes mellitus (n = 1263) diminished from 7.3 to 6.4 mmol/l (p < 0.0001). Conclusion. A fixed combination of enalapril with HCT was effective in hypertensive patients with a high and a very high risk of cardiovascular complications. It provided a target level of blood pressure in 77% patients and significantly reduced SAP, DAP and PAD.

Aim. To determine the role of neurohumoral dysfunction and overweight in a clinical course of arterial hypertension (AH). Material and methods. 200 participants of the study aged 30-60 years with AH degree I-II with low, moderate and high overall cardiovascular risk and mean disease duration 11.1 ± 9.5 years were examined for body mass index, levels of leptin, soluble leptin receptor, insulin, serotonin and adrenoreactivity. Results. Neurohumoral dysfunction correlated with body mass index. It manifested with elevation of insulin and leptin levels, sympathetic hyperactivity and a decrease of serotonin. Conclusion. One of the mechanisms forming and sustaining AH in patients with overweight is leptin-dependent sympathetic hyperactivity while serotonin system activation is more important for patients with normal body weight. Hypertensive patients with obesity demonstrate insulin-dependent hyperleptinemia.

The article presents the history of development of various methods of reperfusion therapy in myocardial infarction. The method of intracoronary thrombolysis was developed and used in Russia in 1976. In 1984 the TIMI Study Group initiated large-scale long-term trial of thrombolytic therapy in myocardial infarction and unstable angina pectoris. Some basic results of the study are outlined.

One of the key causes of lethality in rheumatoid arthritis (RA) are cardiovascular catastrophes (myocardial infarction, stroke, sudden cardiac death) resultant from early development and rapid progression of atherosclerotic vascular lesion. The article presents current approaches to prevention of cardiovascular diseases in RA including assessment of overall cardiovascular risk for design of optimal strategy of correction of modification factors increasing probability of cardiovascular complications, strong control over inflammation and adequate use of drugs which may be harmful (glucocorticosteroids, nonsteroid anti-inflammatory drugs). Much attention is paid to perspectives of ACE inhibitors, angiotensin II receptor blockers, statins, TNFalpha inhibitors in prevention of cardiovaskular complicatoin in RA