[Diagnosis and management of patients with pheochromocytoma/paraganglioma: Consensus of experts of the Russian Medical Society for Arterial Hypertension and the Multidisciplinary Group for the Diagnosis and Treatment of Neuroendocrine Tumors].

The understanding of the nature of catecholamine-secreting tumors has changed significantly in recent years, affecting terminology and classification. Phaeochromocytoma/paraganglioma (PCC/PG) is a rare neuroendocrine tumor from chromaffin tissue that produces and secretes catecholamines. The incidence of PCC/PG is relatively low, with 2-8 cases per 1 million population per year; among patients with arterial hypertension, their prevalence is 0.2-0.6%. However, delayed diagnosis of PCC/PG is associated with a high risk of cardiovascular complications and a high mortality rate. The consensus presents the clinical manifestations of the disease with an emphasis on the course of arterial hypertension as the most common symptom in PCC/PG; modern ideas about the features of diagnosis, aspects of preoperative preparation, treatment, and follow-up of patients with PCC/PG are considered.

[Primary hyperaldosteronism: indications for screening].

The review discusses the current state of the problem of screening patients for early detection of primary hyperaldosteronism (PHA) as a potential cause of arterial hypertension (AH). The features of screening, methodological errors that make it difficult to interpret the results of the study are considered. The screening criteria are analyzed, based on which it is possible to assess the probability of diagnosis of PHA and judge its prevalence in various populations of patients with AH categories of high risk for the development of PHA. Attention is drawn to the low level of screening in patients with AH in order to detect PHA , and to the need for wider familiarization of doctors with the methods of screening and diagnosis of PHA as the cause of uncontrolled AH. The importance of timely diagnosis of PHA and its targeted treatment to reduce the risk of cardiovascular complications associated with hypersecretion of aldosterone is emphasized.

[Russian Medical Society for Arterial Hypertension expert consensus. Resistant hypertension: detection and management].

The diagnosis of resistant arterial hypertension allows us to single out a separate group of patients in whom it is necessary to use special diagnostic methods and approaches to treatment. Elimination of reversible factors leading to the development of resistant arterial hypertension, such as non-adherence to therapy, inappropriate therapy, secondary forms of arterial hypertension, leads to an improvement in the patient's prognosis. Most patients with resistant hypertension should be evaluated to rule out primary aldosteronism, renal artery stenosis, chronic kidney disease, and obstructive sleep apnea. The algorithm for examining patients, recommendations for lifestyle changes and a step-by-step therapy plan can improve blood pressure control. It is optative to use the most simplified treatment regimen and long-acting combined drugs. For a separate category of patients, it is advisable to perform radiofrequency denervation of the renal arteries.

[24-hour systolic wave increment index monitoring in patients with low-renin arterial hypertension].

AIM: To analyze the circadian rhythm of blood pressure (BP) and daily reflected wave values in patients with low-renin hypertension with normal and elevated aldosterone production. SUBJECTS AND METHODS: The investigation included 66 patients. 24-hour BP monitoring was carried out and arterial wall rigidity and reflected wave values were assessed in all the patients. RESULTS: The patients with hyperaldosteronemia were found to have not only statistically significant severer hypertension, impaired circadian rhythms of BP, but also impaired augmentation index (Aix)--mainly its nocturnal increase. A positive correlation was found between nocturnal Aix and resting plasma aldosterone concentrations (r = -0.31; p = 0.002). CONCLUSION: The findings suggest the expediency of 24-hour systolic wave increment index monitoring in hypertensive patients ofthis category.

[Changes in orthogonal ECG in hypertensive patients taking different antihypertensive therapy].

AIM: To ascertain changes in orthogonal ECG in hypertensive patients taking different antihypertensive treatment. MATERIAL AND METHODS: Orthogonal ECG parameters and those of 24-h blood pressure monitoring (BPM) were examined before and after antihypertensive treatment with different drugs in 95 hypertensive patients aged 47 +/- 1 years. Of them, 14 patients received trandolapril+verapamil SR for 2 months, 13 patients--candesartan for 3 months, 25 patients--ramipril for 5 months, 26 patients--carvedilol for 4 months, 10 patients--atenolol for 8 months, 7 patients--doxasozine for 5 months. RESULTS: 24-h BPM parameters improved in all the groups. Initially, conventional ECG evidence on left ventricular hypertrophy was not seen in 86% patients. Dynamics of orthogonal ECG showed that parameters which increase in left ventricular hypertrophy decrease in response to treatment in patients with baseline values above the median. Parameters G and Gx, which in left ventricular hypertrophy diminish, rise significantly in patients with baseline values under median due to therapy. Treatment with impact on renin-angiotensin system reduced voltage parameters of orthogonal ECG, improved G characterizing repolarisation. Treatment with adrenoreceptors blockers reduced IADI. CONCLUSION: The analysis of parameters of orthogonal ECG reveals positive dynamics in response to treatment in patients with insignificant changes on ECG in short follow-up. Drugs of different groups change different parameters of orthogonal ECG.

[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.

[The role of tissue myocardial dopplerechocardiography in early detection of structural-functional changes in the myocardium of patients with mild and moderate arterial hypertension].

AIM: To study structural and functional changes in left ventricular myocardium (LVM) of patients with mild and moderate arterial hypertension (AH) with application of tissue myocardial dopplerechocardiography (TMD), correlation between these changes and parameters of electrophysiological remodeling and circadian profile of blood pressure. MATERIAL AND METHODS: Forty-give hypertensive patients were divided into two groups: the study group 2A consisted of 28 patients with mild AH (144.2 +/- 5.8/89.4 +/- 6.6 mm Hg), group 2B - of 17 patients with moderate AH (160.5 +/- 9.1/101.3 +/- 10.2 mm Hg). The control group consisted of 10 normotensive subjects. All the patients were examined using standard echocardiography with assessment of transmitral blood flow, tissue doppler investigation, circadian monitoring of blood pressure, electro-, vector- and decartocardiography. RESULTS: No significant differences in standard doppler, electro- and vectorcardiographic parameters between the patients with mild and moderate hypertension were found. LVM mass index and LV wall relative thickness significantly increased both in 2A and 2B groups vs controls (p < 0.05). Most patients of group 2A and 50% patients of group 2B had no alterations in LV geometry. Lower blood pressure was associated with LV concentric remodeling, higher - with concentric and excentric hypertrophy. In the presence of LV remodeling hypertensive patients developed more pronounced disorders of diastolic function according to TMD compared to hypertensive patients with normal LV geometry (p < 0.05). TMD detected LV diastolic disorders in 82% patients of group 2A and in 94% - of group 2B, while transmitral doppler study detected diastolic dysfunction only in 14 and 29% patients, respectively. A significant difference by Em/Am was registered between patients with mild and moderate AH only in the area of the mitral ring at the side of LV posterior wall (p < 0.05). CONCLUSION: TMD is able to detect earleast structural-functional myocardial changes in hypertensive patients and to determine significant differences in LV diastolic disorders in patients with mild and moderate AH. No significant differences in LVM mass, standard doppler, electro- and vector-cardiographic parameters were found between AH patients' groups.

[Changes in parameters of orthogonal ECG in hypertensive patients given combined antihypertensive treatment].

AIM: To evaluate changes in parameters of orthogonal ECG in hypertensive patients on trandolapril+verapamil combination. MATERIAL AND METHODS: Eighteen patients before and after 8-week therapy were examined using orthogonal ECG and 24-h monitoring of blood pressure. Computer processing of orthogonal ECG was made with calculation of some vectorcardiography (VCG) and d mapping parameters. Also, 24-h blood pressure monitoring was made. RESULTS: 8-week therapy significantly reduced mean diurnal and nocturnal systolic and diastolic blood pressure (SBP, DBP), improved their variability. In patients with VCG signs of left ventricular hypertrophy the treatment significantly diminished some VCG parameters. A direct correlation was found between initial diurnal SBP variability and SQRSxyz, SQRSxz; dynamics of nocturnal SBP variability and dynamics of SQRSxyz, SQRSxz and Rx+Sz (r = 0.7; p < 0.05). A direct correlation was between dynamics of SBP and IADI (r = 0.7; p < 0.05). CONCLUSION: Hypertensive patients treated with a fixed combination trandolapril/verapamil exhibit a positive trend not only in parameters of 24-h monitoring of blood pressure but also in parameters of orthogonal ECG.

[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.

[Capacities of computed tomographic angiography in the diagnosis and estimation of the site, pattern, and degree of vascular bed lesion in nonspecific aortoarteritis].

Nonspecific aortoarteritis (NAA) is a chronic inflammatory disease that affects the aorta and its branches. The clinical manifestations of this disease are of a great variety and depend on the site of a lesion and the stage of the disease. A wide range of highly informative noninvasive imaging techniques, such as duplex scanning (DS), magnetic resonance imaging (MRI), and computed tomography (CT) of the aorta and its branches, are used to make a more accurate diagnosis and to determine the site and extent of a vascular bed lesion. The given clinical example suggests that CT angiography of the aorta and its branches is a high-precision technique in determining the site of vascular bed lesion in patients with NAA and the pattern and extent of arterial involvement and that it may be used for both the diagnosis of the disease at its developmental stages and the monitoring of the vessels during pathogenetic therapy.

[Extent and location of lesions in aorta and its main branches in patients with nonspecific aortoarteritis with various genotypes in the region of major histocompatibility complex].

AIM: To elucidate associations between location and extent of lesions of arterial vascular bed in patients with nonspecific aortoarteritis and presence of various alleles of DRB1 gene of HLA class II in patients of Russian ethnicity. MATERIAL AND METHODS: Ultrasonography, magnetic resonance imaging and computed tomography were used for examination of arteries in 25 patients aged 22-69 years. Genotyping of HLA-DRB1 locus was carried out in all patients and in a group of practically healthy subjects of the same ethnic group (controls). RESULTS AND CONCLUSION: Patients compared with controls had significantly higher frequency of class II alleles of HLA-DRB1 gene which corresponded to serological specificity DR1. Subgroup of patients carriers of DR1 allele had significantly less extensive involvement of arterial vasculature compared with subgroup of carriers of other alleles. The revealed clinical-genetic relationship reflects special features of aortoarteritis in Russian population and evidence for genetic heterogeneity of this disease.

[Activity of chymotrypsin-like proteinases in patients with ischemic heart disease, arterial hypertension and nonspecific aortic arteritis]. / Aktivnost' khimotripsinopodobnykh proteinaz u bol'nykh ishemicheskoi bolezn'iu serdtsa, arterial'nymi gipertoniiami i nespetsificheskim aortoarteritom.

AIM: To analyze activity of chymotrypsin-like plasma proteinases (CTP) in patients with various cardiovascular diseases. MATERIAL AND METHODS: CTP activity was studied in 82 patients with various cardiovascular diseases: 13 coronary heart disease patients with normal arterial pressure, 49 patients with essential hypertension (EH) and secondary arterial hypertension, 20 patients with nonspecific aortic arteritis. 28 donors served control. RESULTS: CTP activity in plasma of patients with EH rose 4 times compared to donors. If EH patients had concurrent diseases (CHD, chronic pyelonephritis, atherosclerosis of extracranial arteries), CTP activity may increase by 30-300%. In patients with nonspecific aortic arteritis CTP activity in blood plasma is 17.5 times higher than in donors. CONCLUSION: High CTP activity in cardiovascular patients may be explained by chymase and cathepsin G release into blood flow indicating activation of alternative to ACE pathway of angiotensin II production or the presence of the inflammatory process.

[Left ventricular myocardial structure and function in patients with primary aldosteronism]. / Struktunoe i funktsional'noe sostoianie miokarda levogo zheludochka u bol'nykh s pervichnym al'dosteronizmom.

AIM: To study severity of left ventricular hypertrophy (LVH) and left ventricular function in patients with primary aldosteronism (PA) in comparison with hyperaldosteronemia and preoperative arterial hypertension, to follow the dynamics of these parameters early and late after surgical removal of aldosteroma. MATERIALS AND METHODS: Concentration of aldosterone (AC), plasma renin activity (PRA) were measured in 28 PA patients aged 26-58 years before removal of aldosteroma and 1 month, 1 year and 2-5 years after the surgical treatment. Myocardial status was assessed by echocardiography, Doppler echocardiography. 30 healthy subjects aged 25-55 years served control. RESULTS: All the PA patients showed initial or moderate LVH. Index of left ventricular myocardial mass was influenced at the first regression step by primarily diastolic pressure, at the second step--by basal PRA. The diastolic function was affected. One month after unilateral adrenalectomy PRA level and arterial pressure decreased but regression of LVH was noted only 1 year and later after the surgery. Diastolic function improved 1 year after the operation but without normalization within 2-5-year follow-up. CONCLUSION: The lack of a complete normalization of diastolic function of the left ventricle late after the surgery despite regression of LVH and preoperative correlation of the isometric relaxation time with PRA level may be caused by fibrous changes in the myocardium and by hyperaldosteronemia effects.

[Histochemical characteristics of aldosteromas and adrenal tissue of patients with primary hyperaldosteronism]. / Gistokhimicheskaia kharakteristika al'dosterom i adrenalovoi tkani bol'nykh s pervichnym giperal'dosteronizmom.

The authors analyze the data of histochemical examinations of 30 patients with tumorous and nontumorous forms of low-renin hyperaldosteronism, as well as the findings of clinical and hormonal examinations of these patients. The activities of enzymes involved in steroidogenesis (3-beta OSD, NAD and NADP tetrazolium reductases, G-6-PD) were measured, as were levels and distribution patterns of lipids involved in steroidogenesis (free and bound cholesterol, etc.). A high functional activity of aldosteromas of any structure was proved, and a trend to increase of steroidogenic activity of malignant aldosteromas demonstrated. Atrophic changes in the cortex adjacent to aldosteroma were found to involve no reduction of adrenal tissue functional activity. In contrast to this, hyperplastic changes in the cortex adjacent to adenoma were characterized by a lower level of functional activity as against adrenal tissue activity in nontumorous hyperaldosteronism. The authors come to a conclusion that adrenocortical elements hyperplasia associated with some aldosteromas does not participate in aldosterone hyperproduction whereas hyperaldosteronism in nontumorous variants is caused by cortical cell hyperplasia and hormone hyperproduction.

[Effects of surgical treatment on circadian variations of arterial pressure in patients with primary aldosteronism and renovascular hypertension]. / Vliianie operativnogo lecheniia na tsirkadnye kolebaniia arterial'nogo davleniia u bol'nykh pervichnym al'dosteronizmom i renovaskuliarnoi gipertoniei.

Noninvasive recording of blood pressure (BP) with a portable Del Mar Avionics monitor (USA) revealed its abnormal circadian rhythm in patients with renovascular hypertension or arterial hypertension caused by adrenal aldosteroma. Surgical treatment was shown to result in a significant decrease in blood pressures and normalization of its circadian rhythm in the early postoperative period.

[Potential of pulsed Doppler echocardiography in assessing the phasic activity of the left ventricle in patients with symptomatic arterial hypertension]. / Vozmozhnosti impul'snoi dopplerékhokardiografii v otsenke fazovoi deiatel'nosti levogo zheludochka u bol'nykh simptomaticheskimi arterial'nymi gipertoniiami.

The phasic structure of heart activity was explored in 50 patients suffering from symptomatic arterial hypertensions before and after the operative treatment with the aid of impulse Doppler echocardiography. Of these, 28 patients had renovascular hypertension (RVH), 16 primary aldosteronism (PA), and 6 pheochromocytoma of the adrenals. The data obtained were compared with the polycardiographic readings in patients with essential hypertension (EH). As in the case of EH, the period of left ventricular tension, the phase of asynchronous and isometric contraction, and the phase of isometric relaxation became significantly longer in patients with RVH and PA. In the postoperative period, some phases of heart activity return to normal whereas other phases remained altered throughout the entire observation period, which may be due to the disease standing and irreversibility of myocardial alterations. Therefore, Doppler echocardiography is a sufficiently accurate method of estimating phasic activity of the left ventricle, allowing computation of the period of cardiac cycle phases even in the presence of only one lead of the ECG mounted into an ultrasonic outfit.