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Taras Nykula, doctor of medicine, full professor
Vitaliy Bondur, , candidate of medicine
Nataliya Alekseeva, врач-нефролог
Ivan Pasko, врач-кардиолог
Bogomolets National Medical University, Ukraine
Championship participant: the National Research Analytics Championship - "Ukraine";
the Open European-Asian Research Analytics Championship;
В работе представлены материалы по изучению вариабельности сердечного ритма у больных хронической болезнью почек. У больных с поражением почек и артериальной гипертензией имеет место гиперсимпатикотония. Приведены аргументы в пользу назначения ингибиторов ангиотензин-превращающего фермента. Дискутабельным остается вопрос о месте бета-адреноблокаторов.
Ключевые слова: хроническая болезнь почек, вариабельность сердечного ритма, ингибиторы ангиотензин-превращающего фермента.
This paper presents information on the study of heart rate variability in patients with chronic kidney disease. In patients with renal disease and hypertension occurs hypersympathicotonia. Arguments are given in favor of the use of angiotensin-converting enzyme. Debated is the question of the place of beta-blockers.
Keywords: chronic kidney disease, heart rate variability, angiotensin-converting enzyme.
Recent years, more attention is given to identifying predictors of sudden death in patients with chronic kidney disease: glomerulonephritis, a heart rhythm disorder, the presence of concomitant coronary artery disease and hypertension. Monitoring of blood pressure and heart rate helps to clarify aspects of the pathogenesis of the disease and prescribe adequate treatment to nephrology patients, prevent complications of the cardio-vascular system.
This paper presents the results of a study of heart rate variability (HRV) in patients with chronic kidney disease of I-III stages: glomerulonephritis, the dynamics of these parameters under the influence of antihypertensive therapy, the appropriateness of the use of beta-blockers (nebivolol) and/or ACE inhibitors (perindopril). We have studied patients with chronic kidney disease (glomerulonephritis; hypertensive), who unlike healthy ones faced prevalence of sympathetic tone, accompanied by a temporary decrease in HRV. Thus, the daily value of SDNNi, characterizing the total HRV, was on average by 41.1% lower than in the healthy group, in the passive period - by 94.23% during the active period - at 41.26 (p < 0.001). Accurate daily measure of the heart rate interval difference, rMSSD, was 42.64% lower in patients with hypertension than in those without, respectively rMSSD in the active period was lower by 42,33%, rMSSD in the passive period - by 53.23% (p < 0.001).
The average value of pNN50 among the three subgroups of patients was reduced by 70,45%, pNN50 during the active period - at 62.13%, and pNN50 in the passive period - by 72.58% compared to the healthy group (p < 0.001 ).
HF daily index, which reflects the influence of the parasympathetic division of the ANS on cardiac activity was lower by an average of 41.42% as compared to healthy individuals, respectively HF during the active period - at 42.15% in the passive period - at 43.72%.
In contrast, thedaily output was higher for low frequency spectrum night LF, reflecting the sympathetic influence on heart rate: respectively, in average - 14.64 at%, the active period - at 21.15% in passive period - 3.12%(p <0.001) as compared with the group of healthy.
In the main groupsympathetic/parasympathetic balance offset was also observed in favor of the sympathetic division of the ANS, the rate of daily LF / HF was higher by an average of 49.34%, i.e. in patients with hypertension noted the predominance of sympathetic activity.
In a study of 17 patients in the control group receiving antihypertensive drug enalapril maleate 20 mg twice daily, found that under its influence have improved baroreflex regulation of hemodynamics, reduced sympathetic activity.
When comparing the percentage of fluctuations of high, low and very low frequencies of patients in the control group marked decline in the percentage of slow - wave 1 - the first order with 16,72 ± 2,07 to 13,27 ± 2,12; slow waves of 2 - order - with 51,18 ± 6,94 to 45,90 ± 6,46, increase in the proportion of tidal waves from 32,27 ± 6,77 to 40,81 ± 7,57 (Fig.1, Table 1.) .
Fig. 1 Percentage of LF, VLF, HF patients in the control group
Dynamics of changes in the spectral parameters of HRV in patients of the control
group (n = 17) under the influence of enalapril maleate
Under the influence of enalapril maleate in the control group, there was a significant decrease in both systolic blood pressure by 26.08 mm Hg and diastolic 13.90 mm Hg (Table 2).
Dynamics of changes in systolic and diastolic blood pressure in patients in the control group (n = 17)
under the influence of enalapril maleate
Kind of blood pressure
Stable positive effect in hypertensive patients in the control group was accompanied by a subjective improvement in general condition (decreasing intensity of the brain and anginal pain, improving of memory, decrease of the overall weakness etc.) and was confirmed by echocardiography (reduction of left ventricular hypertrophy in 48% of patients), electrocardiogram (the tendency to normalization of the ST segment in 51% of patients).
The decrease in sympathetic nervous system in patients with glomerulonephritis under the influence of ACE inhibitor treatment is a positive predictor in the progression of chronic kidney disease. Correction of autonomic imbalance with enalapril maleate is suitable both in the complex treatment of patients with chronic kidney disease and in the prevention of cardio-vascular complications in the rehabilitation of nephrology patients. There was a relation between the magnitude of blood pressure and weakening of baroreflex regulation with increased sympathetic influences (in patients with severe hypertension power VLF increases, the power of LF-components therein is low).
Under the influence of antihypertensive therapy along with anti-hypertensive effect there was a positive change of HRV. In the study group (n = 32) treated with perindopril reduction was observed of the clinical manifestations of the underlying disease, lowering blood pressure, the positive dynamics of the autonomic regulation of the cardiovascular system (Table 3), namely the reduction of sympathetic activity (reduction of low-frequency power the spectral components of heart rate - VLF from 51,64 ± 13,98% to 35,38 ± 11,56%) and an increase in parasympathetic activity (increased power of high-frequency components - HF from 28,67 ± 9,54% to 31,34 ± 9.54%). An effect on the baroreflex regulation is marked: the capacity of the midrange spectrum component has been increased - LF from 21.34 ± 8.05% to 28.38 ± 9.54%, p < 0.05.
Dynamics of HRV in patients with chronic kidney disease (glomerulonephritis)
who received ACE inhibitors, perindopril
Chronic kidney disease: glomerulonephritis, perindopril
Before treatment (M±σ)
Sympathetic- vagal index, LF/ HF
Dynamics of HRV in patients with chronic kidney disease (glomerulonephritis) who received nebivolol
CKD: glomerulonephritis, nebivolol (n = 26)
Before treatment (M±σ)
Sympathetic-vagal index, LF/HF
This was observed in a statistically significant (p <0,001) increase of the time parameters of ANS: SDNNi daily in a group of perindopril + nebivolol increased by 35.8% than in the control group (standard) - by 32.2%, SDNNi active period - at 32.76% in the control group at 28.3%, SDNNi passive period - of 36.23% (27.5%) (p < 0.001). Daily SDNN in a group of perindopril + nebivolol increased by 34.3% (control – 23.6%), SDNN during the active period increased by 33.1% (control - by 22.2%), SDNN in the passive period increased by 19.3% (control - 11.8%). Other time parameters changed similarly: daily rMSSD decreased by 54.5% (control - by 39,8%), rMSSD in the active period increased by 51.33% (control - by 45,6%), rMSSD a passive period increased by 57.23% (control - 39.4%, p <0.001).Sympathetic-parasympathetic balance under the influence of antihypertensive therapy returned to normal in most patients (falling by 34.45% in the group of perindopril + nebivolol; by 39.2% in the control group).
HF indicator, showing the effect of parasympathetic cardiac activity grew by 38.9% in the control group to 32.4%, the power spectrum of low frequencies, by contrast, tended to lower: in the group with perindopril + nebivolol by 23.4%, in the group control - by 15.4%.
No statistically significant differences between the groups perindopril, nebivolol and perindopril + nebivolol were fixed, but the trend toward normalization in the perindopril group + nebivolol was more expressed when compared the groups of perindopril and control, where enalapril was used, expressed positive changes were observed in the HRV perindopril group (Figure 2).
Figure 2. Dynamics of HRV in patients with chronic kidney disease
(glomerulonephritis) who received ACE inhibitors, perindopril, nebivolol.
It should be noted that the effectiveness of treatment vasoregulatory disorders was higher in patients with chronic kidney disease stage I: glomerulonephritis , and in patients with nephrotic form and pronounced chronic kidney disease stage III: glomerulonephritis in 34.5% of cases it was failed to achieve the correction of autonomic regulation.
Thus, the research revealed signs of autonomic dysfunction in patients with chronic kidney disease: glomerulonephritis with hypertension, the incidence of which increases with a decrease in the glomerular filtration rate. Autonomic imbalance manifests dominated hypersympathicotonia. Nebivolol therapy with perindopril and enforce under vegetative-normalizing and vegetative-corrective effects, and perindopril + nebivolol provides both vegetative normalization and vegetative correction, manifested by reduced and stabilization of blood pressure.