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Analysis of hemodynamic parameters and quality of life in

patients with chronic kidney disease and arterial hypertension

Tamara Muratovna Khokonova *

Sofiat Khasenovna Sizhazheva **

Zhaneta Huseynovna Sabanchieva ***

Marina Tembulatovna Nalchikova ****

Jannet Anvarovna Elmurzayeva *****

Dzhanneta Magometovna Urusbieva ******

Inara Aslanovna Khakuasheva *******

Svetlana Sergeevna Solyanik ********

ABSTRACT

Purpose. The work is devoted to study the effects of antihypertensive, lipid-lowering and metabolic therapy

in office and the average hemodynamic parameters, the parameters of central pressure in the aorta, vascular

wall stiffness and quality of life in patients with CKD stage 3 in combination with arterial hypertension of 1-

2

degrees, and without it. Materials and methods. Were examined patients with arterial hypertension of 1-

degrees and CKD stage 3. Measured hemodynamic parameters with the help of a daily BP monitor

“

BPLab”. The quality of life of patients was assessed by the questionnaire MOS SF36. Results. The greatest

changes in the indicators of central hemodynamics and vascular stiffness were noted in the group of patients

with comorbidity. Conclusion. The combination of antihypertensive therapy (losartan and diltiazem) with

meldonium and rosuvastatin significantly decreases indices of central and peripheral hemodynamics and

vascular stiffness. Add meldonium part of therapy significantly improves the quality of life of patients.

KEY WORDS: antihypertensive therapy; arterial hypertension; central aortic pressure; chronic kidney

disease; hemodynamic parameters; vascular stiffness.

*

(

Candidate of Medical sciences, Senior lecturer of the Department of Microbiology, Virology and immunology

course of Pharmacology) Kabardino-Balkarian state University named after H.M. Berbekov Nalchik, Russia.

ORCID: https://orcid.org/0000-0002-7292-4929 E-mail: sofiat.sizhazheva@mail.ru

*

* Assistant of the Department of Faculty therapy Kabardino-Balkarian state University named after H.M.

Berbekov Nalchik, Russia. ORCID: https://orcid.org/0000-0002-4412-6700

*** Professor of Department of General practice, Gerontology, Public health and Health of medical faculty

Kabardino-Balkarian state University named after H.M. Berbekov Nalchik, Russia. ORCID:

https://orcid.org/0000-0002-9103-0648

**** Candidate of Medical sciences, Associate Professor of Department of Infectious diseases Kabardino-

Balkarian state University named after H.M. Berbekov Nalchik, Russia. ORCID: 0000-0001-9394-3603

*

**** Candidate of Medical sciences, Associate Professor of the Department of Microbiology, Virology and

immunology Kabardino-Balkarian state University named after H.M. Berbekov Nalchik, Russia. ORCID:

https://orcid.org/0000-0002-5640-6638

****** Candidate of Medical sciences, Associate Professor of Department of Faculty therapy Kabardino-

Balkarian state University named after H.M. Berbekov Nalchik, Russia. ORCID: 0000-0002-0259-5293

******* Assistant at the Department of Faculty Therapy Kabardino-Balkarian state University named after H.M.

Berbekov Nalchik, Russia. ORCID: https://orcid.org/0000-0003-2621-0068

*

*******Assistant of the Department of Pharmacy (course of Pharmacology, clinical pharmacology) Kabardino-

Balkarian state University named after H.M. Berbekov Nalchik, Russia. ORCID: 0000-0001-5586-0137

Recibido: 29/01/2021

Aceptado: 26/03/2021

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Análisis de parámetros hemodinámicos y de calidad de vida en

pacientes con enfermedad renal crónica e hipertensión arterial

RESUMEN

Propósito. En el trabajo se estudian los efectos de la terapia antihipertensiva,

hipolipemiante y metabólica en el consultorio y los parámetros hemodinámicos medios, los

parámetros de presión central en la aorta, rigidez de la pared vascular y calidad de vida en

pacientes con ERC estadio 3, en combinación con hipertensión arterial de 1-2 grados, y sin

ella. Materiales y métodos. Se examinaron pacientes con hipertensión arterial de 1-2 grados

y ERC en estadio 3. Se midieron los parámetros hemodinámicos con la ayuda de un monitor

de PA diario “BPLab”. La calidad de vida de los pacientes se evaluó mediante el cuestionario

MOS SF36. Resultados. Los mayores cambios en los indicadores de hemodinámica central y

rigidez vascular se observaron en el grupo de pacientes con comorbilidad. Conclusión. La

combinación de terapia antihipertensiva (losartán y diltiazem) con meldonium y

rosuvastatina disminuye significativamente los índices de hemodinámica central y

periférica y rigidez vascular. Agregar meldonium como parte de la terapia mejora

significativamente la calidad de vida de los pacientes.

PALABRAS CLAVE: terapia antihipertensiva; hipertensión arterial; presión aórtica central;

enfermedad renal crónica; parámetros hemodinámicos; rigidez vascular.

Introduction

Ensuring the greatest possible reduction in the risk of cardiovascular complications,

which involves not only normalizing the level of blood pressure (BP), but also correcting all

modifiable risk factors, preventing or ensuring the reverse development of target organ

damage, and treating associated clinical conditions, is the main goal of controlling blood

pressure.

Damage to the kidneys as target organs in hypertension (AH) has attracted the

attention of a large number of researchers in recent years (Williams et al., 2018; Matsushita

et al., 2010). It has been proven that there is a high incidence of a combination of chronic

kidney disease (CKD) with hypertension, chronic heart failure, and diabetes mellitus (The

Committee of experts of the Russian society of cardiology et al., 2014; Smirnov et al., 2012;

Nedogoda, 2005).

Kidney disease is the most common cause of secondary AH. According to various

authors, hypertension at various stages of development of chronic kidney disease is

observed in 85-100 % of cases. In the structure of complications of CKD, especially in

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chronic renal failure (CRF), the AH syndrome occupies one of the leading places regardless

of etiological factors. There are close pathophysiological correlations between hypertension

and the functional state of the kidneys. Thus, impaired renal function, consisting in

insufficient excretion of sodium and water, is considered the most important pathogenetic

link in increasing BP. Hypertension contributes to kidney damage due to vasoconstriction,

structural changes in the renal arterioles, and parenchymal ischemia (Matsushita, K., van

der Velde, M., Astor, B.C. et al., 2010).

The existing evidence base for the use of meldonium (Mildronate) in clinical practice

indicates the multifaceted effect of the drug in coronary heart disease. Carnitine-dependent

and carnitine-independent mechanisms of action provide the antianginal, anti-ischemic and

vasoprotective effect of meldonium with stable angina pectoris and chronic heart failure.

Additional properties have been identified that determine the structurally modifying effect

on the myocardium, antiarrhythmic, improving carbohydrate and lipid metabolism

(

Trisvetova E.L., 2019).

However, the literature does not adequately cover the issues related to the

development of CKD in young patients with hypertension of 1–2 degrees, and the factors

affecting the development of CKD in these patients have not been studied.

To assess the effect of various antihypertensive therapy (AHT) options on the

clinical outcomes of AH, in recent years they began to consider their effect on the

parameters of central aortic pressure (CAP) and reflected wave index (augmentation index

-

IA) (Ivanov et al., 2008; Kobalava and Kotovskaya, 2015; Nedogoda and Chalyabi, 2006;

Martynov, 2007; Olejnikov et al., 2009; Pshenicin and Mazur, 2007; Gosse et al., 2005).

Antihypertensive drugs differently affect both the nature of the pulse wave and the

parameters of central hemodynamics, despite the same ability to lower blood pressure in

the brachial artery (Rogoza et al., 2008; Chen et al., 1997; Laurent et al., 2006).

Objective: to study the effect of antihypertensive, lipid-lowering, and metabolic

therapy on office and average daily hemodynamic parameters, CAP parameters, vascular

wall stiffness and quality of life (QOL) in patients with stage 3 CKD, both in combination

with and without grade 1-2 hypertension.

1

. Material and methods

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The object of the study was patients treated in the nephrology and cardiology

departments of the Republican Clinical Hospital of the Kabardino-Balkarian Republic, as

well as outpatients who were observed in polyclinics of the city of Nalchik. The criteria for

inclusion of the patient in group 1 were as follows: the presence of CKD C3 (eGFR 30-60 ml

/

min) in combination with AH of the 1st and 2nd degree, age from 45 to 72 years, duration

of AH no more than 10 years, lack of regular AHT. The criteria for inclusion of the patient in

group 2 were as follows: the presence of AH of the 1st and 2nd degree, age from 45 to 72

years, the duration of AH no more than 10 years, the absence of regular AHT. The criteria

for inclusion of the patient in group 3 were as follows: the presence of CKD C3 (eGFR 30-

6

0 ml / min), age from 45 to 72 years. For the control group, patients were selected who,

according to the examination (general clinical examination, biochemical blood test, special

interrogative), statistical, as well as comparative and system analysis methods) were found

to be healthy.

The first group consisted of 45 patients with CKD C3 (eGFR 30-60 ml / min) in

(

combination with hypertension of 1-2 degrees (average age 60 ± 9 years). The group

consists of 19 men and 26 women. The second group consisted of 45 patients with AH of 1-2

degrees without CKD. The third group consisted of 45 patients with CKD C3 without

hypertension. The fourth (control) group consisted of 30 clinically healthy individuals. All

formed groups were comparable by age and gender.

Office hemodynamic parameters and average daily parameters of CDA were

measured using the BPLab daily blood pressure monitor with an expanded version of the

BPLab Vasotens and BPLab Vasotens office software by Petr Telegin (Russia) before

treatment and after 8 weeks of treatment.

QOL of patients was assessed using the MOS SF36 questionnaire before treatment

and within 8 weeks after treatment. The following indicators were calculated: physical

health (PH), which includes physical activity (PA), role-based physical functioning (PF),

physical pain (PP), and general health (GH); Mental health (MH): vitality (V), social

activity (SA), role-playing emotional functioning (EF), as well as a comparison of patients'

well-being (WB).

Statistical processing was performed using the Statistica 10.0 application package.

The arithmetic mean and standard deviations of the studied values and the

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representativeness errors were calculated. The normal distribution of the obtained data was

presented in the form M ± m, where M is the arithmetic mean of the studied quantities, m is

the error of representativeness. The difference in indicators in the groups was evaluated by

t-student test. The significance level of the difference p = 0.05 was considered critical.

2

. Research results and discussion

The clinical characteristics of the examined patients and the received therapy are

presented in tables 1 and 2.

Table 1. Clinical and demographic characteristics of the examined patients

1

st group

2

nd group

3rd group

(CKD III)

n = 45

4th group

(healthy)

n = 30

(CKD III +

Indicator

(AH)

AH)

n = 45

60±9

n = 45

Average age, years

Men, n (%)

62±10

22 (49)

23 (51)

11 (24) *

60±9

20 (44)

25 (56)

12 (27) *

0 (0)

59±11

14 (46)

16 (54)

0 (0)

19 (42)

26 (58)

11 (24) *

Women, n (%)

Smokers, n (%)

AH, n (%)

45 (100) *

20 (44) *

25 (56) *

45 (100) *

21 (47) *

24 (53) *

0 (0)

1

degree, n (%)

degrees, n (%)

0 (0)

2

0 (0)

CHF (1-2 FC according

to NYHA), n (%)

0

(0)

0 (0)

Potassium, meq / L

4,8±0,85**

143±3,29

444±89

4,8±0,57*

136±3,35

342±85

4,9±0,88**

142±2,84

374±87

4,2±0,44

138±3,12

272±91

Sodium, meq / L

Uric Acid, μmol / L

Hemoglobin level. g / l

Hematocrit%

137±23

138±16

136±24

137±15

38,94±5,83

1,47±0,43*

37±6,4

41,83±5,14

0,88±0,11

41±5,1

39,48±6,60

1,38±0,37*

39±5,5

41,18±4,16

0,73±0,17

42±5,4

Blood creatinine, mg / dl

Serum Albumin, g / l

Albuminuria, mg / day

Left ventricular

8,4±3,1 *

3,46±0,7

7,3±2,7 *

3,08± 0,7

1

0 (22) *

8 (18) *

0 (0)

hypertrophy, n (%)

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Glomerular filtration

4

7,5±11,1**

75,4±7,5

45,9±11,7**

106,8±14,5

rate according to CKD-

EPI, ml / min / 1.73 m2

Scale CHA2DS2-VASc,

points

5

±1*

5 (100) *

,84±0,9*

,323±0,6

,1±0,5

,6±0,6

3±1

2±1

4

45 (100) *

5,91±0,8*

45 (100) *

5,92±1,0*

0 (0)

Hyperlipidemia, n (%)

Total cholesterol, mmol /

l

Low density lipoprotein

cholesterol, mmol / L

High density lipoprotein

cholesterol, mmol / L

5

3,8±0,5

3

3,05±0,7

3,24±0,6

2,1±0,6

1

1,2±0,6

1,7±0,6

1,1±0,5

1,6±0,5

1,9±0,4

1,9±1,2

1

Triglycerides, mmol / L

Note: * - p <0.05, ** - p <0.01, *** - p <0.001 - in comparison with the control group

Table 2. Types of pharmacotherapy in the examined patients

Groups

Received therapy

1

. Losartan # 100 mg in the morning at 8.00

2. Diltiazem ## 180 mg 1 time per day

1

(CKD III + AH),

n = 45

3. Rosuvastatin ### 10 mg in the evening at 20.00

4

. Meldonium #### 500 mg 2 times a day at 8.00 and at 14.00

1

. Losartan 100 mg in the morning at 8.00

2. Diltiazem 180 mg once daily

2

(AH),

n = 45

3. Rosuvastatin 10 mg in the evening at 20.00

. Meldonium 500 mg 2 times a day at 8.00 and at 14.00

1. Rosuvastatin 10 mg in the evening at 20.00

4

3

(CKD III),

n = 45

2. Meldonium 500 mg 2 times a day at 8.00 and at 14.00

# Blocktran, Pharmstandard-Leksredstva OJSC, Russia

## Diltiazem Lannacher retard, “Lannacher Heilmittel GmbH”, Austria

### Akorta, Pharmstandard-Tomskkhimfarm OJSC, Russia

#### Mildronat, JSC "Grindeks", Latvia

Information about the patients of the studied groups obtained by monitoring office

hemodynamic parameters before and after treatment are presented in table 3.

From the results of the study it can be seen that the initial office hemodynamic

parameters studied in all patients in the groups were higher than those of the average daily.

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Based on the data obtained, it is seen that the largest changes in office hemodynamic

parameters and vascular stiffness parameters (SBP on the arm, SBP on the ankle, DBP,

MAP, PBP, HR, PWP, PWVao, AIx, dPdt, SAI, CAVIa) were noted in the group of patients

with combined pathology - CKD and hypertension (table. 3).

The smallest deviations from the reference indicators were observed in the group of

patients with CAP without hypertension. It is noteworthy that this group of patients

initially also had an increase in the values of office hemodynamics and vascular stiffness,

such as: SBP on the arm, SBP on the ankle, DBP, MAP, PBP, PWP, PWVao, AIx, dPdt, SAI,

CAVIa) as well as the daily parameters of CDA (SAPao, MAPao, PBPao, AIx (Table 4). This

indicates the presence of close cardiorenal relationships, which are reflected not only by

morphofunctional impairment of renal regulation, but also by the presence of hemodynamic

disorders and arterial endothelial dysfunction, mainly manifested by an increase their

vascular.

When analyzing the daily indices of central hemodynamics, it is seen that the largest

changes in CAP indices (SAPao, DBPao, MAPao, PBPao, Aix) were noted in the group of

patients with combined pathology - CKD and hypertension (Table 4).

In the group of patients with CKD without hypertension, a significant increase in

the values of some indicators of central hemodynamics, such as: SAPao, PBPao, AIx, was

initially observed (Table 4).

Table 3. Dynamics of office hemodynamic parameters in combination therapy

1

st group

2nd group

(AH)

4th group

rd group (CKD)

(healthy)

n = 30

3

Indicator

(

CKD + AH)

n = 45

Originally

152,3±5,72***

134,2 ±4,82*^#

148,4±4,24**

129,5± 4,25*^#

132,1±5,47*

124,2±2,63

SBP, mmHg

Arm)

1

13,4±3,52

After

treatment

(

Originally

179,8±4,57***

168,3±3,59***

153,6±3,94*^#

153,5±4,11*

148,6±3,73

SBP, mmHg

Ankle)

1

41,7±3,47

(

After

treatment

1

59,5±4,06*^#^#

89,2±3,83**

Originally

After

treatment

85,8±3,73*

73±3,04^#

78.4±2,92*

71,2±2,74

DBP, mmHg

70,2±3,27

7

8±2,73*^#

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Originally

After

treatment

Originally

139,6±4,91**

121,4±2,01*^#^#

72,3±4,74**

136,4±2,53**

116,8±2,81^#^#

124,7±2,22*

121,1±3,02

MAP,

mmHg

110,5±2,82

39±3,23

68,6±3,53**

47,2±2,92^#^#

76,5±2,89*

74,6±2,15

48±2,35*

43,8±2,19

71,6±2,32

70,2±1,96

PBP, mmHg

After

treatment

Originally

After

treatment

5

2,5±2,63*^#^#

82,4±3,13**

6,2±2,04*^#

HR, bpm

PTT, ms

69±2,04

7

Originally

After

treatment

Originally

After

treatment

Originally

159,3±4,63***

149±4,74***

131,1±3,18**

117,7±2,74

₃₂_,₈_±₃_,₈₃_*##

₁₂₃_,₈_±₃_,₂₅###

₁₂₀_,₂_±₂_,₉₃#

1

19,2±1,92**

17,5±1,77**

9,6±1,64^#

12,3±1,41*

8,8±1,5

PWVao, m / s

AIx, %

7,2±1,82

1

0,3±1,81^#^#

44,7±4,73***

25,2±3,92^#^#

38,5±3,26**

23,6±3,51^#^#

28,8±3,69*

21,7±3,12

18,5±2,83

After

Originally 1090,74±92,14*** 892,85±69,95*** 525,52±45,25**

dPdt,

mmHg / s

336,46±22,3

6

After

treatment

Originally

₀₉_,₇₅_±₆₈_,₁₅_*_*_*# ₆₈₃_,₅₈_±₅₅_,₂₇_*_*#

₄₂₅_,₂₄_±₅₃_,₄₁#

8

25,32,52***

,22,25^#^#

28,19±2,36***

4,62±1,74*^#

19,71,51***

7,81,14^#^#

9,211,08*

5,81,13^#

SAI, mmHg

CAVia

4,91,7

After

treatment

9

Originally

26,11±2,02**

22,93±2,61*

23,4±2,43*

18,3±1,62

15,2±1,47

2

Note: SBP - systolic blood pressure, DBP - diastolic blood pressure,

MAP - mean arterial pressure, PBP - Pulse arterial pressure,

HR - heart rate, PWP - pulse wave propagation time,

PWVao - pulse wave velocity, AIx - augmentation index,

dPdt is the rate of increase in blood pressure, SAI is the systolic area index,

CAVIa - cardio-ankle vascular index,

*

- the differences are significant in relation to the indicators of the healthy comparison

group (p˂0.05),

** - p <0.01,

*** - p <0.001;

#

- the differences are significant in relation to the initial indicators (p˂0.05),

# - p <0.01, ### - p <0.001

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Table 4. The dynamics of the daily values of CDA in combination therapy

1

group

2 group

(AH)

3 group

(CKD)

4 group

CDA indicators

(

CKD + AH)

(healthy)

SAPao, mmHg - before

treatment / after treatment

139,6±5,29*/ 135,9±2,22*/ 125,1±2,23*/

1

10,4±2,37

##

###

1

21,5±2,23

1,7±3,82*/

117,5±2,64

120,9±3,17

76,4±1,78/

8

79,3±1,70*/

72,5±1,12^#^#

DBPao, mmHg - before

treatment / after treatment

7

3,1±0,78

73,4±1,73^#

75,8±1,35

86,4±2,35/

85,7±1,89

1

05,8±5,73**/ 100,1±3,45*/

MAPao, mmHg - before

treatment / after treatment

8

3,4±1,12

88,5±1,69^#^#

84,3±2,37^#^#

6

0,7±3,65**

6

7,3±4,09***/

45,3±1,68*/

40,9±1,16^#

PBPao, mmHg - before

treatment / after treatment

*/

37,7±1,36

44,7±1,61^#^#^#

4

1,3±1,92^#^#^#

Aortic Augmentation Index

3

6,6±4,41***/ 27,7±3,52**/ 23,3±2,09*/

(

AIx),% - before treatment -

before treatment / after

treatment

1

6,1±1,22

20,2±2,13^#^#19,4±1,65^#

20,3±2,15

Aortic augmentation index

3

2,6±4,44**/ 27,4±3,21**/ 23,2±2,06*/

21,2±2,72^#20,7±3,62^#

21,3±2,76

(

AIx,%, reduced to HR = 75

bpm - before treatment /

after treatment

1

7,6±1,86

Note: SAPao - systolic aortic arterial pressure; DBPao - diastolic aortic blood pressure;

MAPao - mean aortic arterial pressure; PBPao - central pulse blood pressure; Aix - aortic

augmentation index;

*

- the differences are significant in relation to the indices of the healthy comparison group

(

p˂0.05), ** - p <0.01, *** - p <0.001; # - differences are significant in relation to the initial

indicators (p˂0.05), ## - p <0.01, ### - p <0.001

Against the background of combined antihypertensive, lipid-correcting and

metabolic therapy in patients of the 1st and 2nd groups, a significant decrease in the indices

of central and peripheral hemodynamics was noted (Table 3, Table 4).

A group of patients with CKD without hypertension (group 3) who received lipid-

lowering and metabolic therapy (rosuvastatin and meldonium, respectively) during

treatment experienced a decrease in both office hemodynamics and vascular stiffness (SBP

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on the arm, SBP on the ankle, DBP, MAP, PBP, PWP, PWVao, AIx, dPdt, SAI, CAVIa), as

well as initially increased daily CAP parameters (SAPao, PBPao, AIx) (Table 3, Table 4).

However, significant changes during treatment were observed only in the parameters of the

pulse wave propagation time (PWP), the rate of increase in blood pressure (dPdt), the

systolic area index (SAI) (Table 3), as well as in terms of the central pulse blood pressure

(

PBPao) (table 4).

Indicators QOL in patients of the 1st, 2nd and 3rd groups were initially comparable.

An analysis of QOL indices revealed a reliable, statistically significant improvement in QOL

in patients of the 1st and 2nd groups according to the following scales: physical functioning,

vital activity, social functioning, role-based emotional functioning, mental health, as well as

the psychological component of health (Fig. 1a, 1b).

In patients of the 3rd group, significant improvement was noted only on the scales of

physical health, while on the scales characterizing mental health, the observed positive

dynamics was unreliable (Fig. 1c).

The results of the study showed that a more significant dynamics of QOL indicators

was observed in patients of the 1st and 2nd groups, who received meldonium at a dose of

1

000 mg per day along with AHT (Figs. 1a, 1b).

Conclusions

Thus, the initial office studied hemodynamic parameters in all patients in the groups

were higher than those of the average daily. In patients with stage 3 CKD, according to the

study of daily monitoring of blood pressure, elevated indicators of central and peripheral

hemodynamics are detected. An increase in both office hemodynamic parameters and CAP

parameters, stiffness, and a decrease in arterial bed elasticity are most pronounced in

patients with stage 3 CKD in combination with hypertension. The combination of AHT

(

losartan and diltiazem) with meldonium and rosuvastatin significantly reduces the central

and peripheral hemodynamics and vascular stiffness in patients with stage 3 CKD with

hypertension. In patients with grade 1 and 2 hypertension, as well as in patients with stage

3

CKD, in combination with hypertension, who received meldonium at a dose of 1000 mg

per day as part of combination therapy, a significant dynamic of quality of life indicators

was observed.

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POINTS

100

9

8

7

6

5

4

3

0

**

*

**

a

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b

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c

Fig. 1. Dynamics of QOL parameters of patients of the 1st (a), 2nd (b), 3rd (c) groups during

treatment.

Note: ** - differences with the initial indicator are statistically significant, p <0.05, ** - p

<0.01, *** - p <0.001

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