Biomarkers of Inflammation in Predicting the Outcomes of Heart Failure of Ischemic Etiology: the Results of Factor Analysis

Aim. To study the prognostic significance of inflammatory biomarkers in patients with chronic heart failure (CHF) and stenotic multivessel coronary atherosclerosis, with determination of the biomarker separate set that reflects subclinical inflammation and is associated with the development of cardiovascular complications during prospective observation.

Material and methods. A prospective observational study was conducted that included 80 patients with CHF and ischemic heart disease who were scheduled for coronary artery bypass grafting (CABG) during their current hospitalization. In addition to routine clinical laboratory tests, coagulation parameters were evaluated and the following inflammatory biomarkers were determined: neutrophil gelatinase-associated lipocalin (NGAL), growth/differentiation factor 15 (GDF-15), fibroblast growth factor 23 (FGF-23), transforming growth factor beta-1 (TGF-β1), and high-sensitivity C-reactive protein. Also, the calculated neutrophil-to-lymphocyte ratio (N LR) was included in the analysis. Follow-up duration was at least 12 months (median 16 [13, 22] months). Statistical analysis of the data was performed with the IBM SPSS Statistics 21 software.

Results. The study presented results of a factor analysis of 10 inflammatory biomarkers in patients who were scheduled for CABG. One of the factors identified by the analysis included the levels of NGAL and GDF-15, N LR, and the level of fibrinogen in the blood in CHF patients with stenotic coronary atherosclerosis and was significantly associated with the death rate during prospective observation. Furthermore, this association remained significant even after adjustments for age, glomerular filtration rate, severity of heart and coronary insufficiency, and the presence of diabetes mellitus.

Conclusion. In patients with CHF and stenotic coronary atherosclerosis, a set of inflammatory markers, including blood NGAL, GDF-15, N LR, and fibrinogen, can be combined into one factor reflecting subclinical inflammation. The value of this factor can be used to predict cardiovascular death in the long term after surgical myocardial revascularization. 

1. Tereshchenko S.N., Galyavich A.S., Uskach T.M., Ageev F.T., Arutyunov G.P., Begrambekova Yu.L. et al. 2020 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2020;25(11):311–74. DOI: 10.15829/1560-4071-2020-4083

2. Garganeeva A.A., Kuzheleva E.A., Kuzmichkina M.A., Ryabov V.V., Mareev Yu.V., Mareev V.Yu. Characteristics and treatment of patients with heart failure admitted to a cardiology department in 2002 and 2016. Kardiologiia. 2018;58(12S):18–26. DOI: 10.18087/cardio.2605

3. Ageev F.T., Skvortsov A.A., Mareev V.Yu., Belenkov Yu.N. Heart failure on the background of coronary heart disease: some issues of epidemiology, pathogenesis and treatment. Russian Medical Journal. 2000;8(15):622–6.

4. Shirazi LF, Bissett J, Romeo F, Mehta JL. Role of Inflammation in Heart Failure. Current Atherosclerosis Reports. 2017;19(6):27. DOI: 10.1007/s11883-017-0660-3

5. Kuzheleva E.A., Fedyunina V.A., Garganeeva A.A. Patterns of immunological reactions in the pathogenesis of chronic heart failure: review. Kardiologiia. 2021;61(12):94–104. DOI: 10.18087/cardio.2021.12.n1598

6. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2021;42(36):3599–726. DOI: 10.1093/eurheartj/ehab368

7. Vasyuk Yu.A., Kopeleva M.V., Korneeva O.N., Krikunov P.V., Ryabov V.V., Surkova E.A. et al. Recommendations for quantifying the structure and function of heart chambers. Russian Journal of Cardiology. 2012;17(4s4):1–28.

8. Afari ME, Bhat T. Neutrophil to lymphocyte ratio (NLR) and cardiovascular diseases: an update. Expert Review of Cardiovascular Therapy. 2016;14(5):573–7. DOI: 10.1586/14779072.2016.1154788

9. Kalogeropoulos AP, Georgiopoulou VV, Butler J. From Risk Factors to Structural Heart Disease: The Role of Inflammation. Heart Failure Clinics. 2012;8(1):113–23. DOI: 10.1016/j.hfc.2011.08.002

10. Perry TE, Muehlschlegel JD, Liu K-Y, Fox AA, Collard CD, Shernan SK et al. Plasma Neutrophil Gelatinase-Associated Lipocalin and Acute Postoperative Kidney Injury in Adult Cardiac Surgical Patients. Anesthesia & Analgesia. 2010;110(6):1541–7. DOI: 10.1213/ANE.0b013e3181da938e

11. Ghonemy T, Amro G. Plasma neutrophil gelatinase-associated lipocalin (NGAL) and plasma cystatin C (CysC) as biomarker of acute kidney injury after cardiac surgery. Saudi Journal of Kidney Diseases and Transplantation. 2014;25(3):582–8. DOI: 10.4103/1319-2442.132194

12. Morikawa M, Derynck R, Miyazono K. TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harbor Perspectives in Biology. 2016;8(5):a021873. DOI: 10.1101/cshperspect.a021873

13. Ungogo MA. Targeting Smad-Mediated TGFß Pathway in Coronary Artery Bypass Graft. Journal of Cardiovascular Pharmacology and Therapeutics. 2021;26(2):119–30. DOI: 10.1177/1074248420951037

14. Stahrenberg R, Edelmann F, Mende M, Kockskämper A, Düngen H-D, Lüers C et al. The novel biomarker growth differentiation factor 15 in heart failure with normal ejection fraction. European Journal of Heart Failure. 2010;12(12):1309–16. DOI: 10.1093/eurjhf/hfq151

15. Mendez Fernandez AB, Ferrero‐Gregori A, Garcia‐Osuna A, Mirabet‐Perez S, Pirla‐Buxo MJ, Cinca‐Cuscullola J et al. Growth differentiation factor 15 as mortality predictor in heart failure patients with non‐reduced ejection fraction. ESC Heart Failure. 2020;7(5):2223–9. DOI: 10.1002/ehf2.12621

16. Dakroub A, A. Nasser S, Younis N, Bhagani H, Al-Dhaheri Y, Pintus G et al. Visfatin: A Possible Role in Cardiovasculo-Metabolic Disorders. Cells. 2020;9(11):2444. DOI: 10.3390/cells9112444

17. Duman H, Özyıldız AG, Bahçeci İ, Duman H, Uslu A, Ergül E. Serum visfatin level is associated with complexity of coronary artery disease in patients with stable angina pectoris. Therapeutic Advances in Cardiovascular Disease. 2019;13:1753944719880448. DOI: 10.1177/1753944719880448

18. Dutka M, Bobiński R, Wojakowski W, Francuz T, Pająk C, Zimmer K. Osteoprotegerin and RANKL-RANK-OPG-TRAIL signalling axis in heart failure and other cardiovascular diseases. Heart Failure Reviews. 2022;27(4):1395–411. DOI: 10.1007/s10741-021-10153-2

19. Melnikov IS, Kozlov SG, Saburova OS, Avtaeva YN, Prokofieva LV, Gabbasov ZA. Current Position on the Role of Monomeric C-reactive Protein in Vascular Pathology and Atherothrombosis. Current Pharmaceutical Design. 2020;26(1):37–43. DOI: 10.2174/1381612825666191216144055

20. Zhou R, Xu J, Luan J, Wang W, Tang X, Huang Y et al. Predictive role of C-reactive protein in sudden death: a meta-analysis of prospective studies. Journal of International Medical Research. 2022;50(2):3000605221079547. DOI: 10.1177/03000605221079547

21. Surma S, Banach M. Fibrinogen and Atherosclerotic Cardiovascular Diseases – Review of the Literature and Clinical Studies. International Journal of Molecular Sciences. 2021;23(1):193. DOI: 10.3390/ijms23010193