CC BY
23
Zakirova Gulnoza Alisherovna, Junior Researcher of the State Institution "Republican Specialized Scientific and Practical Medical Center of Therapy and Medical Rehabilitation", Tashkent, Uzbekistan E-mail: aliya8833@mail.ru Kamilova Umida Kabirovna, Doctor of Science, professor, Deputy Director for Research of the State Institution "Republican Specialized Scientific and Practical Medical Center of Therapy and Medical Rehabilitation", Tashkent, Uzbekistan E-mail: umida_kamilova@mail.ru Rasulova Zulfiya Dadaevna, Doctor of Science, Senior Researcher of the State Institution "Republican Specialized Scientific and Practical Medical Center of Therapy and Medical Rehabilitation", Tashkent, Uzbekistan E-mail: zulye4ka@mail.ru Khakimova Rano Akhmedjanovna, PhD, Senior Researcher of the State Institution "Republican Specialized Scientific and Practical Medical Center of Therapy and Medical Rehabilitation", Tashkent, Uzbekistan
ROLE OF THE NEUROHUMORAL FACTORS IN THE PROGRESSION OF CHRONIC HEART FAILURE AND KIDNEY DYSFUNCTION
Abstract. The interrelation of the levels of brain natriuretic peptide (BNP) and aldosterone (Al) in serum with the parameters of left ventricular remodeling, the degree of chronic heart failure (CHF) and the parameters of kidney dysfunction in patients with CHF were studied. Revealed a significant increase in neurohumoral factors of BNP and Al associated with functional class (FC) of the CHF, the degree of left ventricular (LV) systolic dysfunction and kidney dysfunction.
Keywords: chronic heart failure, kidney dysfunction, brain natriuretic peptide, aldosterone, prognosis.
Chronic heart failure (CHF) is not only a medical, but is the main factor determining the prognosis of CHF, kidney
also a social problem due to the significant prevalence, high dysfunction is also a major predictor of poor prognosis in pa-
mortality rate and high costs of treating patients with CHF tients with CHF, even more significant than the severity of
[11]. The prevalence of CHF among people over 45 years old HF and EF LV [2].
is 2.5%, while its frequency increases with age and about 50% Withglomerularfiltrationrate (GFR) <60ml/min/1.73m2,
of patients, and, despite the use of combination therapy, dies the risk of mortality increases by 2.1 times, with reduced LV
within 5 years [5]. The risk of sudden death in patients with systolic function, the risk of death for patients with renal insuf-
CHF is 5 times higher than the rate of persons not suffering ficiency increases by 3.8 times, with unchanged systolic func-
from heart failure [9]. The mortality of patients depends on tion - 2.9 times [3]. In case of pronounced impairment of LV
the functional class (FC) of CHF and, according to the data myocardial contractility, the decrease in GFR, as a rule, coin-
of the Framingham study, is about 20% per year, and 4-5 year cides with the appearance of another unfavorable marker - an
survival rate is 25-50% [11]. increase in the concentration of natriuretic peptides (NP) and
With the development of CHF, left ventricular (LV) dys- aldosterone (Al) in plasma [3; 9]. Evaluation of the functional
function is the main trigger, and the LV ej ection fraction (EF) status of the kidneys and biomarkers in the serum of patients
with CHF is important for the selection of prophylactic and therapeutic measures [6; 8].
As a biological marker in the diagnosis of CHF, brain NP (BNP) is used, besides BNP and Al plays an important role in the pathogenesis of CHF, and the increase in their level begins with the asymptomatic LV dysfunction [8; 13]. Biological markers allow you to optimize the processes of screening patients, assessing the prognosis and choosing the optimal treatment strategy and evaluating its effectiveness [4; 8].
Purpose. To study the relationship of BNP and Al levels in blood serum with the degree of CHF and the functional state of the kidneys, and their role in the progression of CHF and kidney dysfunction (KD).
Material and methods
Were examined 52 patients with coronary heart disease (CHD) with CHF with I (19 patients), II (21 patients) and III (12 patients) FC CHF, according to the classification of the New York Association of Cardiology. Average age of patients was 62.5 ± 7.96 years. Control group was 30 healthy individuals. All patients were carried out echocardiography (echocardiography), was determined creatinine (Cr) in the serum, calculated by GFR (cGFR) in the formula CKD-EPI [12], the level of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and Al [13]. Well as all patients were distributed on the 2 groups according to the cGFR: 30 < cGFR < < 60 MA/min/1.73M2-14 patients, consistent with 3 stage CKD, and cGFR > 60 MA/min/1.73M2-38 patients. Definition of the level of NT-proBNP and Al serum was carried out by immunoassay (Elisa) with the use of the test system to determine the NT-proBNP used CJSC "Vector Best" (Russia), to determine Al used test system - "Diagnostics Biochem Canada" (Canada) on an immunoassay analyzer Humareader HS "Human" (Germany). Normal indicators were evaluated in the values ofNT-proB-NP less than 125 pcg/ml, aldosterone - less than 199 pcg/ml.
For statistical data processing, the software package Microsoft Office Excel - 2013 is used. Methods of variational parametric and non-parametric statistics are used with the calculation of the arithmetic average of the studied indicator (M), standard deviation (SD), standard errors of the mean (m), relative values (frequency,%), the statistical significance of the measurement results when comparing the average values determined by the criterion Student (t) with the calculation of the error probabilities (p) when checking the normal distributions (by the criterion excess) and the equality of the general variances (F is the Fisher criterion). For a statistically significant changes have taken the level of confidence p < 0.05. Compared groups on the quality characteristics used criteria x2. For the study of dependence between the quantitative variables used correlation analysis with the calculation of the coefficient of linear Pearson's correlation.
Results and discussion
Analysis of data echocardiography showed that with increasing the degree of CHF progressively decreased EF LV as the main index of systolic function. The results of studies have shown that was: in patients with I FC CHF - 51.68 ± 1.63, with II FC CHF - 47.9 ± 2.02, III FC CHF - 35.7 ± 7.68%. In patients with II and III FC CHF marked reduction EF 7.9% (p<0.001) and 44.9% (p<0.001), respectively, in comparison with the indicators I FC CHF.
Final systolic volume (FSV) in patients I, II and III FC CHF was: 56.47 ± 12.63, 74.9 ± 23.99 and 124.75 ± 42.87 ml, respectively. Index of FSV in patients with II and III FC CHF to 24.3% (p < 0.01) and 52.5% (p < 0.001), respectively, more than indicators I FC CHF. Final diastolic volume (FDV) in patients I, II and III FC CHF was: 118.3 ± 25.1 ml, 147.1 ± ± 46.5 ml and 199.00 ± 58.2 ml, respectively. Indicators of FDV in patients with II and III FC CHF to 19.2% (p < 0.05) and 40.3% (p < 0.001), respectively, more than indicators I FC CHF. Growing signs of CHF in patients with III FC accompanied by the more pronounced structural restructuring LV increased the degree of dilatation LV. When analyzing the obtained indicators of EF and their relationship with GFR in the examined patients, a reliable direct correlation dependence of FV and cGFR (r = 0.953) was revealed. The development of CHF is a consequence of an imbalance in the system of the most complex biochemical mechanisms of vasoconstriction and vasodilation. The root cause of such molecular changes is a direct damaging effect on myocardial ischemia and pressure overload. Against this background, physiological compensatory mechanisms are triggered: activation of the sympathoadrenal system (SAS), the renin-angiotensin-aldosterone system (RAAS), the natriuretic peptide systems, the endo-thelin-1 system, and others. Neurohumoral imbalance leads to the progression of LV dysfunction by accelerating myocardial remodeling processes and to a general cardiac overload [4].
Analysis of the initial level of neurohumoral parameters in patients with II and III FC CHF revealed a significant increase in indicators: NTproBNP and Al in the blood plasma compared with the control group, and patients with I FC CHF, which correlated with the degree of CHF (Tab.1).
As can be seen from table 1, in CHF, a significant increase in plasma NT-proBNP and Al was observed, which correlates with an increase in FC CHF: patients with I FC CHF showed an increase in the content of NT-proBNP and Al by 89.5% (p < 0.001) and 70.4% (p < 0.001). in patients with II FC CHF - by 94.6% (p < 0.001) and 78.2% (p < 0.001). and in patients with FC III - by 96.3% (p < 0.001) and 80.3% (p < 0.001). respectively. compared with the control group. Also, as the increase in FC CHF, a significant increase in NT-proBNP and AL was noted: in patients with FC II CHF by
48.6% (p < 0.05) and by 26.2% (p < 0.01). in patients with respectively, compared with indicators of the first FC CHF FC III CHF - by 65.2% (p < 0.001) and by 33.4% (p < 0.001), patients.
Table 1.- Content of NT-proBNP and Al in plasma in patients with I-III FC CHF (M ± SD)
Indicators Control group (n=30) I FC CHF (n=18) II FC CHF (n=2l) III FC CHF (n=13)
NT-proBNP (pcg/ml) 18.5 ± 9.98 175.37 ± 97.28 *** 341.26 ± 242.77 *** 504.2 ± 86.36 ***
Al (pcg/ml) 54.47 ± 22.66 184.0 ± 46.56 * 249.39 ± 56.84 **** 276.3 ± 45.64 ****
Note: where * - the accuracy of p < 0.05, ** - the accuracy of p < 0.01, *** - the accuracy of p < 0.001 from indicators of the control group
Our results are confirmed by a number of previous studies [6; 15] and showed that in patients with CHF a significant increase in neurohumoral factors: NT-proBNP and Al is associated with the progression of CHF and is a predictor of poor prognosis, reflecting the degree of LV systolic dysfunction. A direct correlation relationship was established between NT-proBNP and Al in patients with FC II and FC III CHF (r = + 0.88 and r = + 0.89, respectively).
Fluctuations in the content of NT-proBNP in patients with I FC CHF ranged from 128 to 556 pcg/ml, and in patients with II FC CHF from 180 to 1023 pcg/ml, and in patients with III FC CHF from 415 to 731 pcg/ml. Similar changes were observed when studying the aldosterone content: fluctuations in the Al content in I FC CHF from 126 to 258 pcg/ml, in II FC CHF from 234 to 334 pcg/ml, and in III FC CHF from 232 to 346 pcg/ml.
The high level of NT-proBNP and Al corresponded to values above the median. Taking into account the fluctuations of these indicators, the distribution of the examined patients according to the content of NT-proBNP and Al was studied within smaller values of the median (medium-high level) and large values of the median (high level).
When analyzing these results, a slight increase in NT-proBNP and Al was found in patients with I FC CHF, while
high values were observed in 5.2% and 21% of patients, respectively, in patients with II FC CHF, a high increase in NT-proBNP and Al was noted in 19% and 90% of the examined patients, respectively, in patients with III FC CHF, a high increase in NT-proBNP was observed in 100% of the examined patients, Al - in 93% of patients. These data suggest that in patients with II FC of CHF, medium-high values of neurohormones prevail, whereas in patients with III FC of CHF, a high level of NT-proBNP and Al increase prevails. Thus, patients with I FC CHF registered low NT-proBNP and Al values, but exceeding the norm, medium-high NT-proBNP and Al values prevailed in patients with II FC CHF and high NT-proBNP and Al values from III FC CHF.
The parameters of neurohormones were analyzed depending on cGFR (Tab. 2). It was noted that NT-proBNP and Al in patients with cGFR < 60 ml/min/1.73 m2 by 56.3% (p < 0.05) and 16.5% (p < 0.05), respectively, were higher by compared with these indicators in patients with cGFR > 60 ml/min/1.73 m2. The correlation relationship between the level of NT-proBNP, Al and EF, FDV was studied. An association of the neurohormones level was revealed: NT-proBNP and Al with heart remodeling: high inverse correlation with EF (r = 0.76 and r = 0.72, respectively) and direct correlation with LV FDV (r = 0.75 and r = 0.70 respectively).
Table 2. The content of NT-proBNP and Al in the blood plasma of patients with cGFR < 60 and cGFR > 60 ml/min/1.73 m2
Indicators Patients with cGFR < 60 ml/min/1.73 m2 Patients with cGFR > 60 ml/min/1.73 m2 P
NT-proBNP (pcg/ml) 409.9 ± 236.97 302 ± 180.0 p < 0.05
Al (pcg/ml) 262.3 ± 138.7 223.97 ± 61.4 p < 0.05
Thus, in patients with CHF, a significant increase in the neurohumoral factors NT-proBNP and Al is associated with FC CHF and indicators of LV remodeling and dysfunction (EF and FDV), as well as kidney dysfunction. In patients with cGFR < 60 ml/min/1.73 m2, the indicators NT-proBNP and Al by 56.3% (p < 0.05) and 16.5% (p < 0.05), respectively, were higher compared with these indicators in patients with cGFR > 60 ml/min/1.73 m2.
Conclusion
In patients with CHF, a significant increase in the neurohumoral factors NT-proBNP and Al is associated with FC CHF, the degree of LV systolic dysfunction and KD. In patients with II FC CHF, the medium-high NT-proBNP and Al values prevailed, and from III FC CHF, a high level of NT-proBNP and Al elevated. A correlation relationship was found between the NT-proBNP, Al and EF levels (r = - 0.70 and r = - 0.72, respectively), between the NT-proBNP, Al and FDV LV (r = 0.78 and r = 0.70, respectively).
References:
1. Kobalava Z. D., Kotovskaya Yu. V., Villevalde S. V., Moiseev V. S. Prospects for the blockade of the renin-angiotensin-aldosterone system and modulation of the natriuretic peptide system in the treatment of arterial hypertension and heart failure. Cardiology. 2015; 6: 72-81.
2. Mezhonov E. M., Vyalkina Yu. A., Shalaev S. V. The prevalence of renal dysfunction, and its effect on the prognosis in patients with acute heart failure. Heart failure. 2017; 18 (2): 87-93.
3. National recommendations. Cardiovascular risk and chronic kidney disease: cardiac nephroprotection strategies. Ed. V. S. Moiseeva, N. A. Mukhina. Russian Journal of Cardiology. 2014; 8 (112): 7-37.
4. Circumcised A. G., Kulikov N. V. Neurohumoral imbalance in chronic heart failure: classic and modern positions. Russian Journal of Cardiology. 2017; 9 (149): 83-92.
5. ESC recommendations on the diagnosis and treatment of acute and chronic heart failure 2016. Russian Journal of Cardiology. 2017; 1 (141): 1-81.
6. Fedotova I. N., Belopolsky A. A., Sturov N. V. Diagnostic significance of NT-proBNP in cardiac patients. Difficult patient. 2013; 7: 32-35.
7. Dienemann T., Fujii N., Orlandi P., Nessel L. et al. International Network of Chronic Kidney Disease cohort studies (iNET-CKD): a global network of chronic kidney disease cohorts. BMC Nephrol. 2016; 17(1): 121.
8. Diez J. Chronic heart failure as a state of reduced effectiveness of the natriuretic peptide system: implications for therapy Eur J Heart Fail. 2017; Feb; 19 (2): 167-76. doi: 10.1002/ ejhf.656.
9. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2016. European Heart Journal. 2016; 37 (27): 2129-2200.
10. Kramer F., Sabbah H. N., Januzzi J. J., Zannad F. Redefining the role of biomarkers in heart failure trials: expert consensus document. Heart Fail Rev. 2017; 22(3): 263-277.
11. Levy M., Wang V. The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective (fee required). Lancet. 2013; 27 (9921): 61752-61763.
12. Sarnak M. J., Bloom R., Muntner P., Rahman M., Saland J. M. et al. KDOQI US commentary on the 2013 KDIGO Clinical Practice Guideline for Lipid Management in CKD. Am J Kidney Dis. 2015; 65(3): 354-66.
13. Veldhuisen D.J., Linssen G. C., Jaarsma T., Gilst W. H. et al. B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. J Am Coll Cardiol. 2013; 61: 1498-1506.
