Prognostic value of depression, anxiety disorders and inflammatory markers in patients with reduced and mildly reduced ejection fraction heart failure

Emine Gazi 1, Elif Karaahmet 2, Hakan Türkön 3, Ahmet Barutçu 1, Uğur Küçük 1 *
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1 Department of Cardiology, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale, Turkey
2 Department of Psychiatry, Sağlık Bilimleri University, Okmeydanı Research and Education Hospital
3 Department of Biochemistry, Meddem Hospital, Isparta
* Corresponding Author
J CLIN MED KAZ, Volume 19, Issue 4, pp. 4-12.
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Aim: Patients with heart failure (HF) have greater rates of depression and anxiety than the general public. The researchers wanted to investigate if there was a relationship between depression, anxiety, and inflammatory markers, as well as survival and hospitalization, in HF patients with reduced and mildly reduced ejection fractions (HFrEF and HFmrEF).
Materials and methods: This prospective research comprised 122 consecutive individuals having a left ventricular ejection fraction (LVEF) of less than 50%. The inflammatory system was investigated using the specific markers. Hamilton Depression and Anxiety Rating Scales (HAM-D and HAM-A) were used to diagnose of depression and anxiety.
Results: The median duration of follow-up was 36.4 months. Non-survivors had lower glomerular filtration rate, LVEF, and blood sodium levels than survivors, while they were older. Age, LVEF, and GFR are independent predictors for mortality. No independent relation was found between depression, anxiety, inflammatory parameters and mortality. Anxiety was found as independent predictors for hospitalization.
Conclusion: Anxiety, depression, and inflammatory conditions indicators were not associated with mortality in people with HFrEF and HFmrEF. Neutrophil-to-lymphocyte ratio (NLR) and anxiety were found as independent predictors for hospitalization.


Gazi E, Karaahmet E, Türkön H, Barutçu A, Küçük U. Prognostic value of depression, anxiety disorders and inflammatory markers in patients with reduced and mildly reduced ejection fraction heart failure. J CLIN MED KAZ. 2022;19(4):4-12.


  • Haworth JE, Moniz-Cook E, Clark AL, Wang M, Waddington R, Cleland JG. Prevalence and predictors of anxiety and depression in a sample of chronic heart failure patients with left ventricular systolic dysfunction. Eur J Heart Fail. 2005;7(5):803-8.
  • Griez EJ, Mammar N, Loirat JC, Djega N, Trochut JN, Bouhour JB. Panic disorder and idiopathic cardiomyopathy. J Psychosom Res. 2000;48(6):585-7.
  • Rutledge T, Reis VA, Linke SE, Greenberg BH, Mills PJ. Depression in heart failure a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes. J Am Coll Cardiol. 2006;48(8):1527-37.
  • Rector TS. A conceptual model of quality of life in relation to heart failure. J Card Fail. 2005;11(3):173-6.
  • Reynolds SL, Haley WE, Kozlenko N. The impact of depressive symptoms and chronic diseases on active life expectancy in older Americans. Am J Geriatr Psychiatry. 2008;16(5):425-32.
  • Sherwood A, Blumenthal JA, Trivedi R, Johnson KS, O'Connor CM, Adams KF Jr, et al. Relationship of depression to death or hospitalization in patients with heart failure. Arch Intern Med. 2007;167(4):367-73.
  • Jiang W, Kuchibhatla M, Clary GL, Cuffe MS, Christopher EJ, Alexander JD, et al. Relationship between depressive symptoms and long-term mortality in patients with heart failure. Am Heart J. 2007;154(1):102-8.
  • Pelle AJ, Pedersen SS, Schiffer AA, Szabó B, Widdershoven JW, Denollet J. Psychological distress and mortality in systolic heart failure. Circ Heart Fail. 2010;3(2):261-7.
  • Torre-Amione G. Immune activation in chronic heart failure. Am J Cardiol. 2005;95(11A):3C-8C; discussion 38C-40C.
  • Sun M, Chen M, Dawood F, Zurawska U, Li JY, Parker T, et al. Tumor necrosis factor-alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state. Circulation. 2007;115(11):1398-407.
  • Penninx BW, Kritchevsky SB, Yaffe K, Newman AB, Simonsick EM, Rubin S, et al. Inflammatory markers and depressed mood in older persons: results from the Health, Aging and Body Composition study. Biol Psychiatry. 2003;54(5):566-72.
  • Bremmer MA, Beekman AT, Deeg DJ, Penninx BW, Dik MG, Hack CE, et al. Inflammatory markers in late-life depression: results from a population-based study. J Affect Disord. 2008;106(3):249-55.
  • Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56-62.
  • Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-5.
  • Ware J E, Kosinski M. SF-36 Physical & Mental Health Summary Scales: A Manual for Users of Version 1. Second ed. Lincoln, Rohode Island: QualityMetric; 2001.
  • Ghosh RK, Ball S, Prasad V, Gupta A. Depression in heart failure: Intricate relationship, pathophysiology and most updated evidence of interventions from recent clinical studies. Int J Cardiol. 2016;224:170-77.
  • Williams SA, Kasl SV, Heiat A, Abramson JL, Krumholz HM, Vaccarino V. Depression and risk of heart failure among the elderly: a prospective community-based study. Psychosom Med. 2002;64(1):6-12.
  • Jünger J, Schellberg D, Müller-Tasch T, Raupp G, Zugck C, Haunstetter A, et al. Depression increasingly predicts mortality in the course of congestive heart failure. Eur J Heart Fail. 2005;7(2):261-7.
  • Mommersteeg PMC, Schoemaker RG, Naudé PJW, Eisel ULM, Garrelds IM, Schalkwijk CG, et al. Depression and markers of inflammation as predictors of all-cause mortality in heart failure. Brain Behav Immun. 2016;57:144-50.
  • Shen BJ, Xu Y, Eisenberg S. Psychosocial and Physiological Predictors of Mortality in Patients of Heart Failure: Independent Effects of Marital Status and C-Reactive Protein. Int J Behav Med. 2017;24(1):83-91.
  • Pelle AJ, Pedersen SS, Schiffer AA, Szabó B, Widdershoven JW, Denollet J. Psychological distress and mortality in systolic heart failure. Circ Heart Fail. 2010;3(2):261-7.
  • Freedland KE, Carney RM, Rich MW, Steinmeyer BC, Skala JA, Dávila-Román VG. Depression and Multiple Rehospitalizations in Patients With Heart Failure. Clin Cardiol. 2016;39(5):257-62.
  • McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, et al. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726.
  • Gottlieb SS, Kop WJ, Ellis SJ, Binkley P, Howlett J, O'Connor C et al. HF-ACTION Investigators. Relation of depression to severity of illness in heart failure (from Heart Failure And a Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]). Am J Cardiol. 2009;103(9):1285-9.
  • Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18-e209.
  • Mann DL. Innate immunity and the failing heart: the cytokine hypothesis revisited. Circ Res. 2015;116(7):1254-68.
  • Horckmans M, Ring L, Duchene J, Santovito D, Schloss MJ, Drechsler M, et al. Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype. Eur Heart J. 2017;38(3):187-197.
  • Kop WJ, Synowski SJ, Gottlieb SS. Depression in heart failure: biobehavioral mechanisms. Heart Fail Clin. 2011;7(1):23-38.
  • Valkanova V, Ebmeier KP, Allan CL. CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord. 2013;150(3):736-44.
  • Högye M, Mándi Y, Csanády M, Sepp R, Buzás K. Comparison of circulating levels of interleukin-6 and tumor necrosis factor-alpha in hypertrophic cardiomyopathy and in idiopathic dilated cardiomyopathy. Am J Cardiol. 2004;94(2):249-51.
  • Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation. 2001;103(16):2055-9.
  • Moorman AJ, Mozaffarian D, Wilkinson CW, Lawler RL, McDonald GB, Crane BA, et al. In patients with heart failure elevated soluble TNF-receptor 1 is associated with higher risk of depression. J Card Fail. 2007;13(9):738-43.
  • Parissis JT, Farmakis D, Nikolaou M, Birmpa D, Bistola V, Paraskevaidis I, et al. Plasma B-type natriuretic peptide and anti-inflammatory cytokine interleukin-10 levels predict adverse clinical outcome in chronic heart failure patients with depressive symptoms: a 1-year follow-up study. Eur J Heart Fail. 2009;11(10):967-72.
  • Redwine LS, Mills PJ, Hong S, Rutledge T, Reis V, Maisel A, et al. Cardiac-related hospitalization and/or death associated with immune dysregulation and symptoms of depression in heart failure patients. Psychosom Med. 2007;69(1):23-9.
  • Johansson P, Lesman-Leegte I, Svensson E, Voors A, van Veldhuisen DJ, Jaarsma T. Depressive symptoms and inflammation in patients hospitalized for heart failure. Am Heart J. 2011;161(6):1053-9.