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7
international Heart and Vascular Disease Journal • Volume 7, № 23, September 2019
Journal of the Cardioprogress Foundation
ORIGINAL ARTICLES
The analysis of office and daily
hemodynamics parameters and pharmacological therapy features in patients with chronic kidney disease and arterial
hypertension
T. M. Khokonova, S. Ch. Sizhazheva, M. A. Umetov, O. Ch. Gyaurgieva, F. M. Shogenova,
D. M. Urusbieva, S. S. Solyanik
Authors
Tamara M. Khokonova, Ph.D., senior teacher of the Department of Microbiology, Virology and Immunology (the course of pharmacology) of Kabardino-Balkar State University named after H M Berbekov, Kabardino-Balkar Republic, Nalchik, Russia
Sofiat Kh. Sizhazheva*, Ph.D., assistant professor of the Department of Internal Medicine of Kabardino-Balkar
State University named after H M Berbekov, Kabardino-Balkar Republic, Nalchik, Russia
Murat A. Umetov, Ph.D., M.D., doctor of sciences, professor, head of the Department of Internal Medicine of
Kabardino-Balkar State University named after H M Berbekov, Kabardino-Balkar Republic, Nalchik, Russia
Fatima M. Shogenova, Ph.D., M.D., docent, methodologist of the Center of Continuing Professional Education,
Professional Retraining and Advanced Education of the Faculty of Medicine of Kabardino-Balkar State
University named after H M Berbekov, Kabardino-Balkar Republic, Nalchik, Russia
Dzhanneta M. Urusbieva, Ph.D., docent of the Department of Internal Medicine of Kabardino-Balkar State
University named after H M Berbekov, Kabardino-Balkar Republic, Nalchik, Russia
Svetlana S. Solyanik, Ph.D., assistant professor of the Department of Internal Medicine of Kabardino-Balkar State University named after H M Berbekov, Kabardino-Balkar Republic, Nalchik, Russia
Objective. To study the effect of antihypertensive, lipid-lowering and metabolic therapy on office and daily hemodynamic parameters, central aortic blood pressure, vascular wall stiffness and life quality in patients with or without 1-2 grade of arterial hypertension (AH).
Kabardino-Balkar State University named after H M Berbekov, Nalchik, Russia
* Corresponding author. Tel.: +7 (967) 429-25-55. E-mail: [email protected]
Materials and methods. We examined patients with 1-2 grade of arterial hypertension (AH) and 3 stage of CKD. Hemodynamic parameters were assessed using daily monitor of arterial pressure «BPLab». Life quality was determined using the MOS SF36 questionnaire.
Results. Patients with AH and CKD had the most significant changes in central hemodynamics and vascular wall stiffness.
Conclusion. The combination of antihypertensive therapy (losartan and diltiazem) with meldonium and rosuvas-tatin significantly reduced central and peripheral hemodynamics and vascular stiffness parameters. Meldonium, added to standard therapy, significantly improves patient's life quality.
Key words: arterial hypertension, chronic kidney disease, central aortic blood pressure, vascular wall stiffness, daily monitoring.
Conflict of interests: none declared.
Received: 25.05.2019 Accepted: 03.07.2019
Introduction
BP control reduces cardiovascular risk and include not only blood pressure (BP) level correction, but also all modifiable risk factors, prevents or treats target organ damage and associated clinical conditions.
Kidney damage in patients with arterial hypertension (AH) has been studied by many researchers over the last years [1,2]. It has been proven that chronic kidney disease (CKD) is associated with AH, chronic heart failure (CHF), and diabetes mellitus [3-5]. However, the association between CKD and 1-2 grade AH in young patients as well as the factors affecting the development of CKD have not been studied enough yet.
The effect of various antihypertensive therapy (AHT) on the outcomes was assessed using central aortic pressure (CAP) and wave reflection index (augmentation index — AIx) over the last years [5-10]. Antihypertensive medications affect pulse wave and central hemodynamics parameters differently, despite the same brachial artery BP reduction [9,13].
Objective
To study the effect of antihypertensive, lipid-lowering and metabolic therapy on office and daily hemodynamic parameters, central aortic blood pressure (CAP), vascular wall stiffness and life quality (LQ) in patients with or without 1st or 2d grade AH.
Materials and methods
Our study included patients from the Department of Nephrology and the Department of Cardiology of Kabardino-Balkar State University named after H M Berbekov of Kabardino-Balkar Republic and am-
bulatory patients from Nalchik city clinics. Group 1 inclusion criteria were: the presence of stage 3 CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min)) in combination with 1st or 2d grade AH, age from 45 to 72 years, duration of AH less than 10 years lack of regular AHT. Group 2 inclusion criteria were: the presence of 1st or 2d grade AH, age from 45 to 72 years, the duration of AH less than 10 years, lack of regular AHT. Group 3 inclusion criteria were: the presence of stage 3 CKD (eGFR 30-60 ml/min), age from 45 to 72 years. The control group included healthy patients according to examination (general clinical examination, biochemical blood test, special (questioning), statistical, as well as comparative and system analysis methods)).
The first group included 45 patients with stage 3 CKD (eGFR 30-60 ml / min) in combination with 1st or 2d degree AH (average age 60±9 years) — 19 men and 26 women. The second group included 45 patients with 1st or 2d grade AH and without CKD. The third group included 45 patients with stage 3 CKD without AH. The fourth (control) group included 30 clinically healthy participants. All the groups were comparable by age and gender.
Office and daily hemodynamic parameters and daily average CAP parameters were measured using the BPLab daily blood pressure monitor with BPLab Vasotens and BPLab Vasotens-office software from Petr Telegin (Russia) before treatment and 8 weeks after.
LQ was assessed using MOS SF36 questionnaire before and 8 weeks after the treatment. The questionnaire included the following parameters: physical health: physical activity, physical functioning, bodily
pain and general health; mental health: vitality, social activity, emotional functioning, as well as a comparison of patients' well-being.
Statistical analysis of obtained data was performed using Statistica 10.0 software. We calculated the arithmetic mean and standard deviations of the parameters and representativeness errors. Normal distribution of obtained data was presented as M±m, where M is the arithmetic mean of studied parameters, m — representativeness error. The significance of differences between groups was assessed using Student's t-test. A p value less than 0.05 was considered significant.
Results
Clinical characteristics of patients and received therapy are presented in tables 1 and 2, respectively.
The results of the office hemodynamic parameters monitoring before and after the treatment are presented in table 3.
The results of the study show that initial office hemodynamic parameters were higher compared with average daily parameters in all the participants. Office hemodynamic and vascular wall stiffness parameters (arm and ankle SBP, DBP, average daily BP,
Table 2. Pharmacological therapy received by participants
Group Received therapy
1 (CKD III+AH), n = 45 1. Losartan 100 mg at 8 a. m. 2. Diltiazem 180 mg once a day 3. Rosuvastatin 10 mg at 8 p.m. 4. Meldonium 500 mg 2 times a day at 8 a.m. and 2 p.m.
2 (AH), n = 45 1. Losartan 100 mg at 8 a. m. 2. Diltiazem 180 mg once a day 3. Rosuvastatin 10 mg at 8 p.m. 4. Meldonium 500 mg 2 times a day at 8 a.m. and 2 p.m.
3 (CKD III), n = 45 1. Rosuvastatin 10 mg at 8 p.m. 2. Meldonium 500 mg 2 times a day at 8 a.m. and 2 p.m.
pulse pressure (PP), heart rate (HR), pulse transit time (PTT), aortic pulse wave velocity (PWVao), augmentation index (AIx), BP rise rate (dPdt), systolic area index (Ssy), cardio-ankle vascular index (CAVIa)) changed significantly in patients with CKD and AH (table 3).
Reference parameters changed less in patients with CKD without AH. It is also remarkable that patients from this group had increased office hemodynamic and vascular wall stiffness parameters: arm SBP, ankle SBP, DBP, average aortic BP, PP, PTT, PWVao, AIx, dPdt, Ssy, CAVIa, as well as CAP param-
Table 1. Clinical and demographical characteristics of participants
Group 1 Group 2 Group 3 Group 4
Parameter (CKD III+AH) (AH) (CKD III) (healthy)
n=45 n=45 n=45 n=30
Average age, years 60±9 62 ±10 60±9 59 ± 11
Men, n (%) 19 (42) 22 (49) 20 (44) 14 (46)
Women, n (%) 26 (58) 23 (51) 25 (56) 16 (54)
Smokers, n (%) 11 (24)* 11 (24)* 12 (27)* 0 (0)
AH, n (%) 45 (100)* 45 (100)* 0 (0) 0 (0)
1st grade AH, n (%) 20 (44)* 21 (47)* 0 (0) 0 (0)
2d grade AH, n (%) 25 (56)* 24 (53)* 0 (0) 0 (0)
CHF (1-2 FC according to NYHA), n (%) 0 (0) 0 (0) 0 (0) 0 (0)
Potassium, mEq/l 4.8±0.85** 4.8±0.57* 4.9± 0.88** 4.2±0.44
Sodium, mEq/l 143±3.29 136±3.35 142±2.84 138 ±3.12
Uric Acid, pmol/L 444± 89 342±85 374±87 272 ± 91
Hemoglobin blood level, g/l 137 ± 23 138 ±16 136 ±24 137 ± 15
Hematocrit, % 38.94± 5.83 41.83 ±5.14 39.48±6.60 41.18±4.16
Creatinine blood level, mg/dl 1.47±0.43* 0.88 ± 0.11 1.38±0.37* 0.73 ± 0.17
Serum albumin level, g/l 37± 6.4 41 ±5.1 39 ±5.5 42± 5.4
Albuminuria, mg/day 8.4±3.1* 3.46±0.7 7.3 ± 2.7* 3.08± 0.7
Left ventricular hypertrophy, n (%) 10 (22)* 8 (18)* 0 (0) 0 (0)
GFR according to CKD-EPI, ml/min/1.73 m2 47.5± 11.1** 75.4±7.5 45.9 ± 11.7** 106.8 ± 14.5
CHA2DS2-VASc score 5±1* 3±1 2± 1 2±1
Hyperlipidemia, n (%) 45 (100) * 45 (100)* 45 (100)* 0 (0)
Total cholesterol, mmol/l 5.84±0.9* 5.91 ±0.8* 5.92± 1.0* 3.8±0.5
Low-density lipoprotein level, mmol/l 3.323± 0.6 3.05±0.7 3.24±0.6 2.1 ±0.6
High-density lipoprotein level, mmol/l 1.1 ±0.5 1.2 ± 0.6 1.1 ±0.5 1.9±0.4
Triglycerides, mmol/l 1.6±0.6 1.7 ± 0.6 1.6 ± 0.5 1.9 ± 1.2
*p<0,05, **p<0,01, ***p<0,001, compared with the control group.
Table 3. The dynamics of office hemodynamic parameters during combinative treatment
Parameter Group 1 (CKD III+AH) n=45 Group 2 (AH) n=45 Group 3 (CKD III) n=45 Group 4 (healthy) n=30
SBP, mmHg (arm) Initially 152.3±5.72*** 148.4±4.24** 132.1 ±5.47* 113.4±3.52
After treatment 134.2 ±4.82** 129.5± 4.25** 124.2 ± 2.63
SBP, mmHg, (ankle) Initially 179.8±4.57*** 168.3 ± 3.59*** 153. 5 ± 4.11 * 141.7 ±3.47
After treatment 159.5±4.06**# 153.6±3.94** 148.6 ±3.73
DBP, mmHg Initially 89.2±3.83** 85.8±3.73* 78.4±2.92* 70.2±3.27
After treatment 78±2.73** 73 ±3.04* 71.2±2.74
Average BP, mm Hg Initially 139.6±4.91 ** 136.4 ± 2.53** 124.7± 2.22* 110.5±2.82
After treatment 121.4±2.01 *## 116.8±2.81** 121.1 ±3.02
PP, mmHg Initially 72.3±4.74** 68.6 ±3.53** 48±2.35* 39 ±3.23
After treatment 52.5±2.63**# 47.2±2.92** 43.8 ± 2. 19
HR, beats per minute Initially 82.4±3.13** 76.5 ±2.89* 71.6±2.32 69 ±2.04
After treatment 76.2±2.04** 74.6 ± 2.15 70.2 ± 1.96
PTT, ms Initially 159.3±4.63*** 149± 4.74*** 131.1 ±3.18** 117.7±2.74
After treatment 132.8 ±3.83*** 123.8±3.25*** 120.2±2.93*
PWVao, ms Initially 19.2±1.92** 17.5 ± 1.77** 12.3± 1.41 * 7.2 ± 1.82
After treatment 10.3 ± 1.81 *# 9.6 ± 1.64* 8.8 ± 1.5
AIx, % Initially 44.7±4.73*** 38.5 ±3.26** 28.8±3.69* 18.5 ± 2.83
After treatment 25.2±3.92** 23.6±3.51** 21.7 ± 3.12
dPdt, mm Hg/s Initially 1090.74±92.14*** 892.85 ±69.95*** 525.52±45.25** 336.46±22.36
After treatment 809.75±68.15***# 683.58± 55.27*** 425.24± 53.41*
Ssy, mm Hg Initially 25.3 ± 2.52*** 19.7 ± 1.51*** 9.21 ± 1.08* 4.9 ± 1.7
After treatment 9.2 ± 2.25" 7.8 ± 1.14™ 5.8 ± 1.13»
CAVIa Initially 28.19 ±2.36*** 26.11 ±2.02** 23.4±2.43* 15.2 ± 1.47
24.62± 1.74** 22.93±2.61* 18.3 ± 1.62
* The differences are significant compared with the control group (p<0,05), ** p<0,01, *** p<0,001;
# The differences are significant compared with the initial paraments (p<0,05); ## — p<0,01, ### — p<0,001.
eters (aortic SBP, average aortic BP, aortic PP, aortic AIx (table 4)).
The most significant differences in CAP (aortic SBP, Average aortic BP, aortic PP, aortic AIx) were registered in patients with CKD and AH, when analyzing daily central hemodynamic parameters (table 4).
Patients with CKD without AH initially had significant increase of some central hemodynamic parameters, such as aortic SBP, aortic PP, aortic AIx (table 4).
Central and peripheral hemodynamic parameters significantly decreased in patients from group 1 and 2
Table 4. The dynamics of daily CAP parameters during combinative treatment
CAP parameters Group 1 (CKD III+AH) n=45 Group 2 (AH) n=45 Group 3 (CKD III) n=45 Group 4 (healthy) n=30
Aortic SBP, mmHg — before/after treatment 139.6 ± 5.29*/ 121. 5 ± 2.23** 135.9±2.22*/ 117.5 ±2.64*** 125.1 ±2.23*/ 120.9 ±3.17 110.4± 2.37
Aortic DBP, mmHg — before/after treatment 81.7±3.82*/ 73.4± 1.73* 79.3± 1.70*/ 72. 5 ± 1. 12** 76.4± 1.78/ 75.8 ± 1.35 73.1 ±0.78
Aortic average BP, mmHg — before/after treatment 105.8± 5.73**/ 88.5 ± 1.69** 100.1 ±3.45*/ 84.3±2.37** 86.4± 2.35/ 85.7 ± 1.89 83.4± 1.12
Central arterial pulse pressure (aortic PP), mmHg — before/ after treatment 67.3±4.09***/ 44.7 ± 1.61 *** 60.7 ± 3.65***/ 41.3 ±1.92*** 45.3 ± 1.68*/ 40.9 ±1.16* 37.7± 1.36
Aortic AIx (Alxao), % before/after treatment 36.6 ± 4.41 ***/ 20.2 ±2.13** 27.7±3.52**/ 19.4± 1.65* 23.3±2.09*/ 20.3 ±2.15 16.1 ±1.22
Aortic AIx (Alxao), %% reduced to HR =75 beats per minute before/ after treatment 32.6±4.44**/ 21.2±2.72* 27.4±3.21 **/ 20.7±3.62* 23.2±2.06*/ 21.3±2.76 17.6 ± 1.86
* The differences are significant compared with the control group (p<0,05), ** p<0,01, *** p<0,001; # The differences are significant
compared with the initial paraments (p<0,05); ## —p<0,01, ### —p<0,001.
during combined antihypertensive, lipid-lowering and metabolic therapy (table 3, 4).
Office hemodynamic and vascular wall stiffness parameters decreased (arm SBP, ankle SBP, DBP, PP, PTT, PWVao, AIx, dPdt, Ssy, CAVIa) and CAP parameters increased (aortic SBP, aortic PP, aortic AIx) (table 3, 4) in patients with CKD without AH (group 3) during antihypertensive and lipid-lowering therapy (meldonium and rosuvastatin, respectively). But the changes were significant only by PTT, dPdt, SsY (table 3) and by aortic PP (table 4) parameters.
LQ parameters between groups were initially comparable. The analysis LQ parameters revealed reliable, statistically significant improvement of the following parameters in patients from groups 1 and 2: physical functioning, vitality, social functioning, emotional functioning, mental health, as well as health psychological component (Figure 1a, 1b).
Physical health parameters significantly improved in patients from group 3, when changes in psychological health parameters were insignificant (Figure 1c).
The best dynamics in LQ parameters were registered in patients from groups 1 and 2 who received AHT and 1000 mg of meldonium per day (Figure 1a and 1b).
Discussion
This study represents features of antihypertensive, lipid-lowering, and metabolic therapy effects on the office and average daily hemodynamic parameters, CAP parameters, vascular wall stiffness and LQ in patients with CKD and AH.
The prognostic significance of CAP and arterial stiffness can be proven by their inclusion into the lat-
est European guidelines on AH (2018) as target organ damage signs [1].
The results of the study showed that the greatest hemodynamics and vascular stiffness parameters increase were observed in patients with CKD and AH.
The smallest changes of reference parameters in patients with CKD without AH, the initial increase in office hemodynamics and vascular stiffness, as well as daily CAP parameters indicate cardiorenal association, which can be presented not only as morpho-functional impairment of renal regulation, but also as hemodynamic and arterial endothelial dysfunction, for example arterial stiffness.
The results of this study reinforce recent studies that have shown an independent inverse correlation between GFR <60 ml/min /1.73 m2 and the number of cardiovascular events. It is also remarkable that CVD occur in patients with renal dysfunction 64 % more often compared with patients with preserved function, and cardiovascular mortality — by 22-35 % [2, 11, 12].
The results of the Chronic Kidney Disease Prognosis Consortium study, which involved over 1 million patients in general population with high-risk and CKD, showed independent from each other and from main cardiovascular risk factors inverse with GFR and direct with albuminuria correlation with general and cardiovascular mortality and with renal outcomes [2].
Thus, further studies on the correlation between central hemodynamic parameters, arterial stiffness and daily blood pressure monitoring in patients with CKD, AH and dyslipidemia are needed.
a)
b)
c)
group 1 (CKD + AH) before treatment group 2 (CKD + AH) 8th week of treatment the control group (healthy).
group 1 (CKD + AH) before treatment group 2 (CKD + AH) 8th week of treatment the control group (healthy).
oa PO TB 03 mc CA
t group 1 (CKD + AH) before treatment
1 group 2 (CKD + AH) 8th week of treatment
B the control group (healthy).
Figure 1. The dynamics of LQ parameters in patients from group 1 (a), group 2 (b) and group 3 (c) during treatment
a) * The differences are significant compared with the control group (p<0,05), ** p<0,01, *** p <0,001; #The differences are significant
compared with the initial paraments (p<0,05); ##p<0,01, ***p<0,001.
b) ** The differences are statistically significant compared with the initial paraments p < 0,05,** p <0,01, *** p <0,001.
Score
Conclusion
Thus, all the patients had higher initial hemodynamic parameters compared with daily parameters. Patients with stage 3 CKD had increased central and peripheral hemodynamic parameters according to daily BP monitoring. Patients with stage 3 CKD and AH had increased office hemodynamic and CAP parameters, arterial stiffness and decreased arterial elasticity.
The combination of antihypertensive therapy (losartan and diltiazem) with meldonium and rosuvastatin significantly reduced central and peripheral hemodynamics and vascular stiffness parameters in patients with stage 3 CKD and AH. Patients with 1 and 2 grade AH as well as with stage 3 CKD with AH, who received 1000 mg meldonium per day, added to standard therapy, had significant life quality improvement.
Conflict of interest: None declared. References
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