Arterial stiffness and wave reflections, which are now well accepted as the most important determinants of increasing systolic and pulse pressures in ageing societies, reflect large artery damage in hypertension. These parameters are increasingly used in the clinical assessment of patients with hypertension and various cardiovascular (CV) risk factors. This review addresses recent advances in our understanding of the role played by arterial stiffness and wave reflection in the pathophysiology and treatment of hypertension. We also report a large number of longitudinal epidemiological studies demonstrating the independent predictive value of arterial stiffness, carotid pulse pressure and augmentation index, for cardiovascular events, and show that these parameters are now well accepted as intermediate end-points for CV events. We also discuss the effects of pharmacological agents on aortic stiffness and wave reflections. A remaining major issue is to determine whether a reduction in PWV or wave reflection in hypertensive patients is associated with a concomitant reduction in CV events, independently of the normalization of classical CV risk factors.

As cardiovascular morbidity and mortality is still representing a challenge in spite of prevention and all treatment efforts, there is a need for new pathophysiological models for better understanding of cardiovascular risk and its treatment. Target organ damage including left ventricular hypertrophy and microalbuminuria is considered to be a mediating step between risk factors and cardiovascular events. Substantial evidence has been accumulated to show that arterial stiffness and increased pulse wave velocity (PWV), as well as central aortic pulse pressure, are important independent predictors of cardiovascular events, and they reflect not only target organ damage but also the underlying pathological process, because increased PWV might determine the degree of left ventricular mass through increased arterial pulse wave reflection, central pulse pressure, and postload. A concept of early (premature) vascular aging is based on perception of arterial wall as an accumulator of damaging effect of classical and other risk factors. This concept may be potentially useful for potential vascular protective treatment strategies.

The paper reviews different research methods of vascular stiffness that is an independent predictor of the cardiovascular pathology and cardiovascular mortality. Vascular stiffness assessment particularly by means of measuring of the pulse wave velocity by carotid femoral method (the «gold standard») allows to diagnose artery damage on pre-clinical stage and to detect people with high cardiovascular risk. Modern techniques allows a noninvasive contour analysis of both peripheral and central pulse wave, measurement of central blood pressure, detection of modifying factors (augmentation, amplification), assessment of the cardiovascular risk, pathogenetic reasonable therapy administration and control.

The present review summarizes data on investigation of arterial stiffness in women during different period of their life and its predictive role in relation to development of gestosis and low-birth-weight infant. Own data is specified on application of applanation tonometry to women with threatened abortion.

Recent developments in the tissue deformation imaging have allowed the cardiologist to objectively quantify regional and global myocardial function. Regional deformation (strain) and deformation rate (strain rate) can be calculated non-invasively in both the left and right ventricle, providing information on regional function in a variety of clinical settings. Although this promising novel technique is increasingly applied in clinical and preclinical research, knowledge about the principles, limitations and technical issues of this technique is mandatory for reliable results and for implementation both in the clinical as well as the scientific field.

Objective. The aim of the study was to assess vascular stiffness in healthy subjects with different cardiovascular risk factors (components of metabolic syndrome) and its relation to other target organ damage. Design and methods. We examined 117 patients having at least one metabolic syndrome component. Left ventricular hypertrophy according to ASE 2006 was detected in 45 %, microalbuminuria - in 27 %, decreased ankle-brachial index - in 24 %, carotid plaques in - 15 %. Results. None of the subjects had pulse wave velocity (PWV, carotid-femoral) more than 12 m/s. PWV was related only to age and blood pressure and correlated with other target organ damage level.

Objective. To study the association between left ventricular myocardium mass (LVM) and office, 24-hour ambulatory blood pressure (BP), and pulse wave velocity (PWV) in young men aged 18-25 years old. Design and methods. 192 men 18-25 years old (mean age 21,0 ± 2,1 years), who showed a rise in BP at casual measurements, were included. Office and 24-hour ambulatory BP were rechecked, applanation tonometry of radial artery wall stiffness with the use of the transfer function of distal (peripheral) PWV into the central one was performed. Based on echocardiography left ventricular mass index (LVMI) and left ventricular wall thickness (LVWT) ratio, disproportionality index (DI) as the ratio between the studied LVM and the normal one were measured. Spearman analysis was performed for assessing the correlation between hemodynamic parameters and LV characteristics. The correlation at p < 0.05 was considered valid. Results. In the studied group a stronger correlation was seen between LVM index and 24-hour ambulatory BP and PWV parameters rather than for office BP. The correlation was stronger between LVM index and systolic BP (SBP, r = 0,36, p < 0,0001) than with central BP (r = 0,25, p < 0,0001), but correlation coefficient was lower for the daytime PP than for the central PP (r = 0,27 and r = 0,30 respectively, p < 0,0001). DI stronger correlated with SBP, measured by 24-hour ambulatory monitoring (r = 0,20, p = 0,003); LVWT ratio - with office (r = 0,34, p = 0,0001), 24-hour ambulatory (r = 0,33, p < 0,0001) and daytime SBP (r = 0,33, p < 0,0001). There is no correlation between central and peripheral BP and LVMI, however a weak correlation with the reflection wave is seen in young men with sustained hypertension (n = 114). Conclusions. In young hypertensive males at the age of 18-25 years old, the level of central BP does not have any clear advantages in predicting changes in LV structure, unlike the 24-hour ambulatory BP that showed a great importance in diagnosing hypertension in young men.

Objective. To evaluate changes in pulse-wave shape and endothelial function (EF) in patients with essential arterial hypertension (AH) treated with calcium-channel blockers (CCB) or inhibitors of angitensin-converting enzyme iACE. Design and methods. Sixty one high-risk hypertesive patients with preserved left ventricular ejection fraction were consequently enrolled in the study and than randomized to CCB or iACE therapy. Also, indapamide or hydrochlorothiazide was administered to most of the patients to achieve blood pressure (BP) goals. Using novel finger photoplethysmographic device AngioScan-01 and traditional ultrasonographic method, endothelial function (EF, in reactive hyperemia test) and pulse-wave characteristics were measured both before and after 5 weeks of treatment. Stiffness index (SI), reflection index (RI), augmentation index (AIx), systolic BP in aorta (SPa), digital pulse amplitude augmentation (by photoplethysmography), and flow-mediated dilation (FMD, by ultrasound) were accessed. Results. The majority of patients at`baseline showed normal SI, and elevated RI, AIx, SPa, and significantly impaired EF . BP goals (< 130/90 mmHg) were achieved in all patients validating further analysis. Decrease in SI (p < 0,05), RI and SPa was found in both treatment arms, whereas trends towards AIx decrease and EF improvement were demonstrated only in iACE group. Also, substantial correlation (r = 0,4, p < 0,05) between finger photoplethysmographic and traditional ultrasonographic EF assessment was found. Conclusions. High-risk hypertensive patients demonstrated increased vascular stiffness and peripheral vasoconstriction, accompanying by impaired EF. Both iACE and CCB treatment resulted in central BP and SI decrease, whereas only iACE therapy was associated with trends in EF and AIx improvement in short-term follow-up. Fair accuracy of photoplethysmographycally in assessment of digital pulse amplitude augmentation (compared with ultrasonographicaly measured flow-mediated dilation) allows to use this simplier and more convenient method in clinical practice.

Objective. The aim of this study was to assess the left ventricular diastolic dysfunction (LVDD) contribution to the development of heart failure (HF) in non-ST-segment elevation myocardial infarction (NSTEMI) patients with metabolic syndrome (MS). Design and methods. 116 consecutive NSTEMI patients were divided into groups according to the presence of MS: group I - 58 patients with MS (25 men, 33 women, mean age 62,9 ± 10,5 years), group II (control) - 58 patients without MS (31 men, 27 women, mean age 62,7 ± 11,9 years). HF was estimated based on the Killip classification. Echocardiography was performed during the first hour of the hospitalization, systolic and diastolic function were assessed. Results. Patients of group I with HF class of Killip II and more, had significantly higher diastolic filling flow velocity DT than patients with Killip I (222,84 ± 50,35 vs. 187,07 ± 39,52 ms, p = 0,03). Besides patients in group I with symptoms of HF showed higher IVRT: 113,94 ± 25,56 ms compared to 98,13 ± 18,43 ms in patients of group I without HF, p = 0,06. Comparative analysis of the diastolic function parameters between the groups showed higher DT in patients of group I in comparison with patients of group II (222,84 ± 50,35 vs. 184,36 ± 53,03 ms, p = 0,04). Left ventricular ejection fraction was reduced in patients with symptoms of HF of the both groups. Conclusions. Symptomatic HF in patients with NSTEMI against the background of MS is determined by the both diastolic and systolic function disturbances.

Background. Nitric oxide synthesized by endothelial nitric oxide synthase plays an important role in endothelial function regulation as well as in blood pressure and heart rate control. Objective. To assess the association between eNOS gene polymorphism intron 4a/4b and hypertension development, tachycardia in patients with clinical thyrotoxicosis. Design and methods. The eNOS gene polymorphisms were examined by polymerase chain reaction. We compared eNOS gene polymorphism 4a4b in 164 patients with clinical thyrotoxicosis. All patients we divided into three groups matching by sex, age, level thyroid hormones: group 1 included patients with eNOS 4b4b polymorphism (n = 111), group 2 - patients with eNOS 4a4b polymorphism (n = 46), group 3 - patients with eNOS 4a4a polymorphism (n = 7). Blood pressure and heart rate were assessed before and after 3-week treatment with β-blocker and angiotensin converting enzyme inhibitors. Result. The eNOS 4a4b polymorphism gene correlates with the blood pressure level and heart rate. Before treatment blood pressure and heart rate were significantly higher in group 1 than in group 3. After treatment blood pressure and heart rate were significantly lower in group 3 in comparison with groups 1 and 2. Conclusion. Our results demonstrate that eNOS polymorphism allele b predisposes to the development of endothelial dysfunction.

Objective. To systematize patients with arterial hypertension (AH) according to the pathogenetic mechanisms of its development and response to antihypertensive therapy. Design and methods. Included 896 patients were included (mean age was (M ± m) 54,0 ± 8,0 years, systolic blood pressure (BP) - 196,3 ± 6,4 mmHg, diastolic BP - 115,0 ± 4,8 mmHg). Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were estimated by radioimmune method at 8-9 hours in the morning while awake state. PRA was rated as normal if ranged 1,0-3,0 ng/ml/h, and PAC - 0, 18-0,83 nmol/l (5-23 ng/dl or 50-230 pg/ml). Conclusions. According to the circulating blood volume, renin-angiotensin-aldosterone and sympathoadrenal system and the response to antihypertensive therapy 16 subgroups of hypertensive patients were formed: 12 of them included patients with essential hypertension, 2 subgroups - with «transitional form of low renin hypertension», and 2 subgroups - with primary hyperaldosteronism.

Objective. To investigate relationship between blood matrix metalloproteinase-1 (ММР-1) and its tissue inhibitor (TIMP-1) levels and clinical data, myocardial mass and diastolic left ventricular dysfunction, circadian blood pressure (BP) indices in hypertensive patients with paroxysmal atrial fibrillation. Design and methods. ММР-1 and TIMP-1 levels by hardphase immunoenzyme analysis were defined in 39 hypertensive patients with paroxysmal atrial fibrillation, and the correlation with the main parameters of echocardiography (including tissue echocardiography) and circadian BP indices was assessed. Results and conclusions. Blood TIMP-1 level positively correlates with pulse BP, its variability, and systolic BP variability that can indirectly indicate the existence of relation between blood TIMP-1 level and the increase of arterial rigidity due to the collagen uptake. Increase of MMP-1 blood level positively associates with the reduction in load index of diastolic BP. We found positive correlation of TIMP-1 levels with thickness of interventricalar septum in diastole. Patients with increased left ventricular (LV) myocardial mass index had significantly higher TIMP-1 level compared to patients with normal myocardial mass index. Patients with concentric and eccentric LV hypertrophy had significantly higher TIMP-1 blood level than patients with LV concentric remodelling and normal geometry that can also indicates an increase of collagen accumulation in myocardium.

The paper addresses evaluation of economic burden of arterial hypertension in real practice in Russia based on epidemiologic and pharmacoepidemiologic studies and the results of OPTIMAX study. Markov model in 10-year time horizon perspective was used to estimate efficacy of fixed combination of Perindorpil and Indapamide (Noliprel, Servier, France) in hypertensive patients. 3 age female and male groups (under 50, 55 and 60 years old) were formed; direct (personal expenses, expenses of public health budget) and indirect costs (loss of salary, collection of taxes, social expenses) were estimated. Treatment with Noliprel is more effective considering life expectancy and prevention of complications in hypertensive patients as compared to usual treatment AH. Antihypertensive therapy used in real practice demonstrates relatively low direct costs, but high indirect costs; with aging direct costs increase and demands in medical assistance and indirect costs decrease. Noliprel use has cost-saving effect, in particular in men under 50 and 55 years old by decreasing economic burden. Despite the growth of personal expenses (Noliprel cost), public health care budget is saved by the decrease of medical assistance demand in all hypertensive groups (about 2,4-10,4 thousand rubles per patient). Cost of 1 QALY (quality-adjusted life year) shows cost-saving effect of Noliprel treatment in male groups under 50 and 55 years old; in other groups additional expenses are under 2 thousand rubles.