CLINICAL CHARACTERISTICS OF MEN AND WOMEN IN YOUNG AND MIDDLE AGE WITH ARTERIAL HYPERTENSION AT DIFFERENT GALECTIN-3 PLASMA LEVELS ACCORDING TO THE RESULT OF LINEAR REGRESSION ANALYSIS

The aim of the research was to describe the clinical charachters of male and female patients with stage II arterial hypertension (AH) of young and middle age with different gradations of galectin-3 plasma levels according to multiple linear stepwise regression


Introduction
Arterial hypertension (AH) is the dominant disease among all cardiovascular diseases (CVD), due to its high prevalence, morbidity and disability, which causes its cardiovascular complications [1,2]. Our present day is marked by a number of works devoted to the search for new biomarkers that participate in the pathogenesis of AH and which affect the course of the disease in male and female patients, young and middle-aged [3,4]. It is galectin-3, a protein in the galectin group that is expressed by many cells, such as neutrophils, macrophages, labrocytes, fibroblasts and osteoclasts, and is involved in many biological processes such as cell growth and proliferation, apoptosis, endogenous inflammation, myocardial fibrosis and others [5,6]. A considerable amount of experimental work indicates that galectin-3 expression is closely associated with myocardial fibrosis [7,8] and type I collagen accumulation, and an increased level of factor is usually associated with progressive myocardial dysfunction [9,10]. To this end, the study concerned the determination 134 clinical, laboratory and instrumental indicators were analyzed as variables (influential factors). The latter were deliberately divided into different groups responsible for fundamentally different patient characteristics. Multiple regression analysis was performed separately for each selected group of factors, the final results were presented in the form of linear regression equations, which showed the most powerful regression relationship between the analyzed parameters and the output parameter.
The informativeness of the obtained regression equation was estimated by the coefficient of determination (R 2 ), which demonstrated the strength of the relationship between the equation variables and the output parameter; the nature of its significance is Fisher's actual and proper F (F) criterion and significance level (p), the standard error of communication -St. Errorofestimate. In the presence of two or more variables in the regression equation, the influence of each variable on the output parameter (neurohormone level) in percent (%) was calculated, which was calculated as the ratio of the beta coefficient of the variable to the sum of the beta coefficients of all variables of the equation.
In addition, a critical level was determined for the quantitative variables -the median of the parameter value calculated for the galectin level is 1.1 and 2.4 pg / ml, which reflect the upper bound of the relatively low (RL) and the lower bound of the relatively high (RH) level of neurohormones in plasma in accordance.

Results
The data in Table 1 characterize the indices that showed the strongest regression associations with galectin-3 levels, which in turn are six completely different groups that characterized: 1) duration of hypertensive history in years -(factor A); 2) the neurohumoral background of the subjects (plasma aldosterone level in pg/mlfactor X); 3) prevailing risk factors (presence of abdominal obesity in points -factor Y and atherogenic dyslipidemia in points -factor D); 4) structural and functional state of the myocardium (presence of concentric myocardial hypertrophy in points -factor K, LAVi in ml/m 2 -factor Z and E/e' aver -factor W); 5) functional status of the valvular apparatus of the heart (presence and nature of mitral regurgitation in points -factor MR and aortic regurgitation in points -factor AR); 6) structural condition of the carotid arteries (carotid IMT value in mm -factor T). The analysis of the coefficients of determination (R 2 ) of the obtained regression equations showed that they obtained the highest values for risk factors (factors Y+D, R 2 =0.63) and the level of aldosterone in plasma (factor X, R 2 =0.62) and the smallest for the duration of the hypertensive history (factor A, R 2 =0.19) and the functional state of the heart valve apparatus (factors MR+AR, R2=0.20). Therefore, the obtained data suggested that in patients with young and middle-aged AH, plasma galectin-3 levels are most closely associated with aldosterone levels and the presence of risk factors such as abdominal obesity and atherogenic dyslipidemia. It is possible to exclude the fact that these factors may determine the peculiarities of AH in patients with different levels of galectin-3.
The positive signs of the coefficients of the variables of the regression equations indicated that all the variables had a direct relationship with the level of galectin-3. The latter could indicate that an increase in the magnitude of all variables should be accompanied by an increase in the level of galectin-3 in plasma and, conversely, higher levels of galectin-3 predicted higher values of the variable regression equations. In this case, the dominant effect on the baseline parameter was abdominal obesity (the effect on the baseline parameter was 85 % versus 15 % for dyslipidemia, respectively); presence of structural-geometric remodeling of the left ventricle (LV) in the form of the most problematic model -concentric LV hypertrophy in combination with myocardial relaxation disorders (E/e' aver>7.2) and signs of hemodynamic LA overload (LAVi>34 ml/m 2 ). The latter factor had the greatest impact on the output parameter compared to the others (the impact strength was 65 % versus 19 % and 16 %, respectively); the presence of valve dysfunctions in the form of mitral (1-2 stage) and aortic regurgitation (1 stage), whereby aortic regurgitation had the highest influence on the initial parameter (62 % vs. 38 % respectively); the presence of structural remodeling of the carotid arteries, characterized by an IMT>0.91 mm.

Note: RL -relatively low and RH -relatively high level
Taking into account the preliminary data on the magnitude of the determination coefficients for the various groups of factors, it should be assumed that plasma galectin-3 level>2.4 pg/ml, were associated, from a clinical point of view, with the presence of metabolic risk factors (primarily, abdominal obesity), and with pathophysiological -hyperactivation of renin-angiotensin-aldosterone system (RAAS), which was confirmed by an increase in aldosterone level >298 pg/ml in the blood plasma of patients with stage II AH.
From the clinical implications, the level of galectin-3 >2.4 pg/ml in plasma will be characterized by a more pronounced and more severe structural remodeling of the cardiovascular system compared to the general population of patients with young and middle-aged AH, namely the presence of concentric hypertrophy with impaired hypertrophy myocardium and more severe hemodynamic atrial overload; more severe structural remodeling of the carotid arteries and development of mitral and aortic regurgitation. The latter clearly demonstrates a more severe course of AH in patients with galectin-3 >2.4 pg/ml in plasma. It is observed that the most informative instrumental marker of RH of galectin-3 levels in patients with young and middle-aged AH is IMT>0.91 mm and LAVi>34 ml/. Therefore, in patients with young and middle-aged AH, plasma galectin-3 levels should be considered as a neurohumoral marker, which is associated with the presence of metabolic risk factors (primarily obesity) and more severe structural and functional lesions of the cardiovascular system structural remodeling of vessels and hemodynamic overload of the heart). The latter provides every reason for clinicians to consider these patients as a group with more severe AH who require the most effective cardio and vasoprotection to improve treatment efficacy. According to the beta coefficients obtained for each variable (reflecting the power of the effect of the variable on the baseline parameter), a scale for the prediction of galectin-3 levels in plasma and, accordingly, the a priori course of AH in young and middle-aged patients was developed. The minimum beta value was taken as 1. All other beta coefficients were divided by the minimum value and the resulting number was rounded to the integer value ( Table 2). Draws attention that the total number of all scores was 39. The highest scores were given by variables such as aldosterone levels >298 pg/ml in plasma (10 points) and the presence of abdominal obesity (9 points). In turn, a minimum score (1 point) was calculated for such features as concentric LV hypertrophy, E/e' aver>7.2 and 2 stage mitral regurgitation. The latter were uninformative for the diagnosis of plasma galectin-3 RH levels.

Discussion
By means of multiple linear regression analysis, the equation for a priori calculation of the level of galectin-3 in plasma was determined according to the points scored according to Table 2. Thus, the plasma level of galectin-3 ≥ points were scored 0.13 pg/ml (R2=0.61, p<0.0001; prediction sensitivity was 63 %, specificity 86 %). A higher specificity indicated that the derived equation more significantly eliminated the RH level of galectin-3 in plasma. According to this equation, it was determined that at least 19 points should be scored for the diagnosis of plasma galectin-3 levels in the plasma.
Undoubtedly, we were interested in predicting the course of AH in young and middle-aged patients, taking into account simple and accessible criteria that general and family practitioners could use. Therefore, the exclusion from the analysis of plasma aldosterone, which resulted in the maximum score (10 points), indicated the need to take into account most of the criteria obtained in clinical and instrumental examination of patients.
It was observed that in patients with abdominal obesity (9 points), in combination with IMT>0.91 mm (6 points) and LAVi>34 ml/m 2 (4 points), plasma galectin-3 RH should be predict-  [13,14], but with IMT [2]. Therefore, the prior plasma galectin-3 level in this case is ≥2.47 pg/ml, which corresponds to its RH level. Instead, in the absence of an abdominal obesity patient, a high level of galectin-3 could only be predicted if all other criteria were summed up to 20 points. Study limitations. When it is impossible to determine the level of aldosterone, the patient's absence of abdominal obesity and IMT≤0.91 mm or LAVi≤34 ml/m 2 or the duration of AH≤4 years, it is unlikely to think about the RH plasma galectin-3 level and a severe AH (total score) will not be 19 points).
Prospects for further researches are that the data obtained for different grades of galectin-3 provide every reason to consider patients with RH galectin-3 as a group with more severe AH and high cardiovascular risk who need the most effective cardio and vasoprotection . The developed risk stratification scales of galectin-3 RH level provide an opportunity to isolate these patients.

Conclusions
It was found that in young and middle-aged patients with AH RH galectin-3 levels are associated with: the presence of a complex of metabolic risk factors -obesity and dyslipidemia; in combination with multiple features of structural and functional changes in the cardiovascular system, such as the presence of concentric LV hypertrophy combined with myocardial relaxation disorders (E/e' aver>7.2) and signs of hemodynamic LA overload (LAVi>34 ml/m 2 ); the presence of valve dysfunctions in the form of mitral (1-2 stage) and aortic regurgitation (1 stage); the presence of structural remodeling of the carotid arteries (IMT> 0.91 mm). The most informative markers of the RH level of galectin-3 in the plasma were the presence of abdominal obesity, IMT>0.91 mm and LAVi>34 ml/m 2 .