Russian Heart Failure Journal 2009year Interrelation between levels of pro-inflammatory factors and severity of heart failure in ischemic heart disease

To access this material please log in or register

Register Authorize

Interrelation between levels of pro-inflammatory factors and severity of heart failure in ischemic heart disease

Belenkov Yu. N., Tatenkulova S. N., Mareev V. Yu., Masenko V. P., Balakhonova T. V., Tripoten M. I., Kaznacheeva E. I., Belyavsky E. A., Tkachev G. A., Zykov K. A.



Urgency. Available literature data suggest that cytokines play an important role in the pathogenesis of inflammation in patients with IHD. However mechanisms underlying development of the inflammation response are not studied in detail; peculiarities of interrelations between components of the immune system are not established; and whether immune disorders are primary or secondary to the CHF pathogenesis in IHD is not known. Aim. Investigation of correlation of proinflammatory factors levels and CHF signs intensity in IHD patients. Materials and methods. Markers of endothelial and left ventricular function and immune activation were studied in 43 patients (41 men (95%) and 2 women (5%)) with I-IIb stage IHD and I–IV FC (NYHA) CHF. Age of patients ranged from 33 to 64 years. Blood levels of high-sensitivity C-reactive protein (hsCRP), immunoglobulins (IgG, IgA, IgM), sIL-2R, IL-8, IL-6, IL-18, IL-10, IFN-γ, NT-proBNP, endothelin (ET), and nitric oxide (NO) were measured. EchoCG was recorded using standard techniques with assessmen of LV systolic and diastolic function. Vasoregulatory endothelial function was studied using a reactive hyperemia (RH) test. Results. Patients were divided into two groups based on the NT-proBNP level. Group 1 included patients with NT-proBNP levels equal to or lower than median (725 pg/mL); Group 2 consisted of patients with NT-proBNP levels higher than median. An association of higher levels of proinflammatory factors (CRP, IL-6, NO metabolites) and severity of heart failure was observed. Endothelial dysfunction and impaired systolic and diastolic heart function were related to elevated markers of inflammation process (Group 1: CRP to ESR and EF; IL-18 to flow-dependent vasodilation and the diastolic function index, Decel time; Group 2: CRP to ESR; IFN-γ to EDV and Decel time). Therefore the data obtained have documented an association between elevated blood levels of inflammation markers and severity of heart failure.
  1. Smith W. Epidemiology of congestive heart failure. Am J Cardiol. 1985; 55 (2):3A-8A.
  2. Czuriga I. Chronic heart failure – the epidemic of the 21st century. Orv Hetil. 2005; 146 (20 Suppl 2):1075–1087.
  3. Kosmala W, Derzhko R, Przewlocka-Kosmala M et al. Plasma levels of TNF-alpha, IL-6, and IL-10 and their relationship with left ventricular diastolic function in patients with stable angina pectoris and preserved left ventricular systolic performance. Coron Artery Dis. 2008; 19 (6):375‑382.
  4. Rugina M, Caras I, Jurcut R et al. Systemic inflammatory markers in patients with aortic sclerosis. Roum Arch Microbiol Immunol. 2007; 66 (1–2):10–16.
  5. Gotsman I, Stabholz A, Planer D et al. Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden? Isr Med Assoc J. 2008; 10 (7):494‑498.
  6. Greig D, Castro P, Gabrielli L et al. [Inflammation and endothelial dysfunction in patients with chronic heart failure] Rev Med Chil. 2008; 136 (6):687‑693.
  7. Guyatt GH, Sullivan MJ, Thompson PJ et al. The 6‑minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J. 1985; 132 (8):919‑923.
  8. Иванова О. В., Балахонова Т. В., Соболева Г. Н. и др. Состояние эндотелийзависимой вазодилатации плечевой артерии у больных гипертонической болезнью, оцениваемое с помощью ультразвука высокого разрешения. Кардиология. 1997; 37 (7):41–45.
  9. Беленков Ю. Н., Агеев Ф. Т., Мареев В. Ю. Нейрогормоны и цитокины при сердечной недостаточности: новая теория старого заболевания? Журнал Сердечная Недостаточность. 2000; 1 (4):35–38.
  10. Bozkurt B, Kribbs SB, Clubb FJ Jr et al. Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats. Circulation. 1998; 97 (14):1382–1391.
  11. Habib FM, Springall DR, Davies GJ et al. Tumour necrosis factor and inducible nitric oxide synthase in dilated cardiomyopathy. Lancet. 1996; 347 (9009):1151–1155.
  12. Torre-Amione G. Immune activation in chronic heart failure. Am J Cardiol 2005; 95 (11A):38C-40C.
  13. Anker SD, Egerer KR, Volk HD et al. Elevated soluble CD14 receptors and altered cytokines in chronic heart failure. Am J Cardiol. 1997; 79 (10):1426–1430.
  14. Niebauer J, Volk HD, Kemp M et al. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet. 1999; 353 (9167):1838–1842.
  15. Michowitz Y, Arbel Y, Wexler D et al. Predictive value of high sensitivity CRP in patients with diastolic heart failure. Int J Cardiol 2008; 125 (3):347‑351.
  16. Ndrepepa G, Kastrati A, Braun S et al. N-terminal probrain natriuretic peptide and C-reactive protein in stable coronary heart disease. Am J Med. 2006 Apr; 119 (4):355.e1-8.
  17. Shlipak MG, Ix JH, Bibbins-Domingo K et al. Biomarkers to predict recurrent cardiovascular disease: the Heart and Soul Study. Am J Med. 2008; 121 (1):50–57.
  18. Ingle L, Rigby AS, Nabb S et al. Clinical determinants of poor six-minute walk test performance in patients with left ventricular systolic dysfunction and no major structural heart disease. Eur J Heart Fail. 2006; 8 (3):321‑325.
  19. Dini FL, Conti U, Fontanive P et al. Prognostic value of N-terminal pro-type-B natriuretic peptide and Doppler left ventricular diastolic variables in patients with chronic systolic heart failure stabilized by therapy. Am J Cardiol. 2008; 102 (4):463‑468.
  20. Iwai Y, Hemmi H, Mizenina O et al. An IFN-gamma-IL-18 signaling loop accelerates memory CD8+ T cell proliferation. PLoS ONE. 2008; 3 (6):e2404.
  21. Kleemann R, Zadelaar S, Kooistra T. Cytokines and atherosclerosis: a comprehensive review of studies in mice. Cardiovasc Res. 2008; 79 (3):360‑376.
  22. Okamoto M, Kato S, Oizumi K et al. Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia. Blood. 2002; 99 (4):1289–1298.
  23. Yamaoka-Tojo M, Tojo T, Inomata T et al. Circulating levels of interleukin 18 reflect etiologies of heart failure: Th1 / Th2 cytokine imbalance exaggerates the pathophysiology of advanced heart failure. J Card Fail. 2002; 8 (1):21–27.
  24. Jurcuţ R, Arsenescu I, Puşcariu T et al. Is interleukin-18 correlated with endothelial dysfunction and platelet activation in patients with unstable angina? Rom J Intern Med. 2005; 43 (3–4):199‑209.
  25. Vanderheyden M, Kersschot E, Paulus WJ. Pro-inflammatory cytokines and endothelium-dependent vasodilation in the forearm. Serial assessment in patients with congestive heart failure. Eur Heart J. 1998; 19 (5):747‑752.
  26. Amosova EN, Shpak YV, Nedozhdij AV, Produsevich LV. Proinflammatory cytokine levels in patients with diastolic heart failure. Kardiol Pol. 2004; 61 (7):17–20.
  27. Fukunaga T, Soejima H, Irie A et al. Relation between CD4+ T-cell activation and severity of chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2007; 100 (3):483‑488.

To access this material please log in or register

Register Authorize
Ru En