Association of genetic, biochemical and functional markers of the condition of the vascular endothelium in chronic heart failure with mid-range ejection fraction

The aim of this study was to analyse genetic (polymorphism 4a/4b gene NOS3), biochemical (endothelin-1) and functional (endothelial function coefficient) markers of a condition of vascular endothelium in patients (n = 65) with chronic heart failure (CHF) with  mid-range ejection fraction (40–49%), depending of the stage of the disease and identify the presence of associations between the  analyzed markers. Somatically healthy people (n = 65) were examined as a control group. A decrease in the value of the endothelial  function coefficient and an increase in the production of endothelin-1 in all groups of patients compared with somatically healthy  people were revealed. The severity of these changes was greater in groups of patients with more severe stage of the disease. The  analysis of polymorphism 4a/4b gene NOS3 in patients with CHF revealed a statistically significant predominance of the number of  patients with a more severe stage of the disease among of patients with polymorphism 4a/4b. Patients with polymorphism 4a/4b  had a statistically significant lower value of the endothelial function coefficient and a higher level of endothelin-1 compared  patients with polymorphism 4b/4b. Thus, polymorphism 4a/4b is characterized by a deeper lesion of the vascular endothelium in  patients with CHF with mid-range ejection fraction and the development of more severe stages of the disease. The obtained data  can be used in the aspect of personalized medicine. 

1. Shvarts Y.G., Akimova N.S., Martynovich T.V. Analysis of changes in white matter of brain and cognitive disturbances in patients with chronic heart failure and ischemic heart disease. Saratov Journal of Medical Scientific Research. 2013;9(1):78-82. (In Russ.)

2. Dushina A.G., Libis R.A. Efficiency of combinations of calcium antagonist with renin-angiotensin-aldosterone system blockers in patients with chronic heart failure with preserved ejection fraction. Arterial Hypertension. 2013;9(1):78-82. (In Russ.)

3. Kopeva K.V., Grakova E.V., Teplyakov A.T. New biomarkers of heart failure: diagnostic and prognostic value of NT-proBNP and interleukin receptor family member ST2. Complex Issues of Cardiovascular Diseases. 2018;7(1):94-101. (In Russ.)

4. DuBrock H.M., AbouEzzeddine O.F., Redfield M.M. High-sensitivity C-reactive protein in heart failure with preserved ejection fraction. PLoS One. 2018;13(8):e0201836.

5. Akhmineeva A.Kh., Polunina O.S. The natriuretic peptide of type C and severity of endothelial dysfunction at bronchial asthma with arterial hypertension. Kuban Medical Science Bulletin [Kubanskij nauchnyj medicinskij vestnik]. 2012;2(131):19-21. (In Russ.)

6. Bajaj N.S., Osborne M.T., Gupta A., Tavakkoli A., Bravo P.E., Vita T., Bibbo C.F. et al. Coronary Microvascular Dysfunction and Cardiovascular Risk in Obese Patients. J Am CollCardiol. 2018;72(7):707-717.

7. Podzolkov V.I., Bragina A.E., Druzhinina N.A. Prognostic significance of endothelial dysfunction markers in arterial hypertension. Russ J Cardiol. 2018;4(156):7-13. (In Russ.)

8. Ivanov A.N., Grechikhin A.A., Norkin I.A., Puchinyan D.M. Methods of endothelial dysfunction diagnosis. Regional Haemodynamics and Microcirculation. 2014;13(4):4-11. (In Russ.)

9. Uklistaya T.A., Guseinov G.T., Polunina O.S., Galimzyanov H.M. The influence of catalaza gene polymorphism on the development of cardiovascular pathology in chronic obstructive pulmonary disease. RUDN Journal of Medicine. 2012, (4): 53-58. (In Russ.)

10. Voronina L.P. Genetic, biochemical and functional markers of condition of vasoregulating function of endothelium. Siberian Medical Journal (Irkutsk). 2011;102(3):29-31. (In Russ.)

11. Persic V., Bastiancic A.L., Rosovic I., Raljevic D., Samsa D.T., Bastiancic L., Miskulin R. et al. Correlation between immunological-inflammatory markers and endothelial disfunction in the early stage of coronary heart disease. Med Hypotheses. 2018;115:72-76. (In Russ.)

12. Akhmineeva A.H., Polunina O.S., Voronina L.P., Sevostyanova I.V. The functional, genetic and biochemical markers of the state of the vascular endothelium in hypertensive disease. Astrakhan Medical Journal. 2013;8(3):40-43. (In Russ.)

13. Rickenbacher P. Heart failure with «mid-range» ejection fraction: a new clinical entity? Ther Umsch. 2018;75(3):170-173.

14. Lopatin Y. Heart Failure with Mid-Range Ejection Fraction and How to Treat It. Card Fail Rev. 2018;4(1):9-13.

15. Mareev V.Yu., Fomin I.V., Ageev F.T., Arutyunov G.P., Begrambekova Yu.L., Belenkov Yu.N., Vasyuk Yu.A. Clinical guidelines. Chronic heart failure (CHF). Russian Heart Failure Journal. 2017, 18(1): 3–40. (In Russ.)

16. Dorodneva E.F., Isakova D.N., Efanov A.Y. Role of endothelin-1 in the development of cardiovascular disease in patients with diabetes. Medical science and education of the Urals. 2013;14(73):172-176. (In Russ.)