A comparative analysis of novel cardiovascular biomarkers in patients with chronic heart failure


      • 4 Novel cardiovascular biomarkers (sST2, GDF-15, suPAR and H-FABP) were analyzed in a collective of heart failure patients.
      • Levels of sST2, suPAR and H-FABP were significantly higher in ICM and DCM patients compared to the control group.
      • H-FABP was found to be the most promising biomarker for the prediction of heart failure.



      Heart failure (HF) with reduced ejection fraction remains a major therapeutic challenge. The aim of this study was to investigate the role of novel cardiovascular biomarkers, i.e. soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) in patients with ischaemic (ICM) or dilative cardiomyopathy (DCM).

      Materials and methods

      A total of 200 patients were enrolled in this study: 65 were diagnosed with DCM and 59 patients suffering from ICM were included. 76 patients without coronary artery disease or signs of heart failure were included as controls. Plasma samples of all patients were analyzed by use of ELISA.


      Levels of sST2, suPAR and H-FABP were significantly higher in ICM and DCM patients compared to the control group (p < 0.0001). However, there were no significant differences between ICM and DCM in biomarker levels. Ejection fraction correlated inversely with cardiac biomarkers (sST2 p < 0.0001, GDF-15 p = 0.0394, suPAR p = 0.0029, H-FABP p < 0.0001). Similarly, CRP levels also showed a positive correlation with cardiac biomarkers. Renal insufficiency (p < 0.0001) and diabetes (sST2 p = 0.0021, GDF-15 p = 0.0055, suPAR p = 0.0339, H-FABP p = 0.0010) were significantly associated with a rise in cardiac biomarkers.


      Novel cardiovascular biomarkers such as ST2, GDF-15, uPAR and H-FABP could offer a great potential for more precise diagnostic in ICM and DCM patients. H-FABP was the most promising marker in our study, followed by sST2, uPAR and GDF-15. Additional prospective studies will be necessary to further evaluate the potential clinical benefits in routine treatment of HF.


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        • Andersson C.
        • Enserro D.
        • Sullivan L.
        • Wang T.J.
        • Januzzi Jr., J.L.
        • Benjamin E.J.
        • et al.
        Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community: the Framingham heart study.
        Atherosclerosis. 2016; 248: 245-251
        • Ben-Gal Y.
        • Mohr R.
        • Feit F.
        • Ohman E.M.
        • Kirtane A.
        • Xu K.
        • et al.
        Surgical versus percutaneous coronary revascularization for multivessel disease in diabetic patients with non-ST-segment-elevation acute coronary syndrome: analysis from the acute catheterization and early intervention triage strategy trial.
        Circulation, Cardiovascular Interventions2015
        • Bleumink G.S.
        • Knetsch A.M.
        • Sturkenboom M.C.
        • Straus S.M.
        • Hofman A.
        • Deckers J.W.
        • et al.
        Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure the Rotterdam study.
        Eur Heart J. 2004; 25: 1614-1619
        • Briasoulis A.
        • Androulakis E.
        • Christophides T.
        • Tousoulis D.
        The role of inflammation and cell death in the pathogenesis, progression and treatment of heart failure.
        Heart Fail Rev. 2016; 21: 169-176
        • Carson P.
        • Wertheimer J.
        • Miller A.
        • O'Connor C.M.
        • Pina I.L.
        • Selzman C.
        • et al.
        The STICH trial (surgical treatment for ischemic heart failure): mode-of-death results.
        JACC Heart Fail. 2013; 1: 400-408
        • Ciccone M.M.
        • Cortese F.
        • Gesualdo M.
        • Riccardi R.
        • Di Nunzio D.
        • Moncelli M.
        • et al.
        A novel cardiac bio-marker: ST2: a review.
        Molecules. 2013; 18: 15314-15328
        • Cook C.
        • Cole G.
        • Asaria P.
        • Jabbour R.
        • Francis D.P.
        The annual global economic burden of heart failure.
        Int J Cardiol. 2014; 171: 368-376
        • Damman P.
        • Kempf T.
        • Windhausen F.
        • van Straalen J.P.
        • Guba-Quint A.
        • Fischer J.
        • et al.
        Growth-differentiation factor 15 for long-term prognostication in patients with non-ST-elevation acute coronary syndrome: an invasive versus conservative treatment in unstable coronary syndromes (ICTUS) substudy.
        Int J Cardiol. 2014; 172: 356-363
        • Eugen-Olsen J.
        • Andersen O.
        • Linneberg A.
        • Ladelund S.
        • Hansen T.W.
        • Langkilde A.
        • et al.
        Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population.
        J Intern Med. 2010; 268: 296-308
        • Hacker S.
        • Lambers C.
        • Pollreisz A.
        • Hoetzenecker K.
        • Lichtenauer M.
        • Mangold A.
        • et al.
        Increased soluble serum markers caspase-cleaved cytokeratin-18, histones, and ST2 indicate apoptotic turnover and chronic immune response in COPD.
        J Clin Lab Anal. 2009; 23: 372-379
        • Hanley J.A.
        • McNeil B.J.
        The meaning and use of the area under a receiver operating characteristic (ROC) curve.
        Radiology. 1982; 143: 29-36
        • Hausenloy D.J.
        • Botker H.E.
        • Engstrom T.
        • Erlinge D.
        • Heusch G.
        • Ibanez B.
        • et al.
        Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations.
        Eur Heart J. 2016;
        • Japp A.G.
        • Gulati A.
        • Cook S.A.
        • Cowie M.R.
        • Prasad S.K.
        The diagnosis and evaluation of dilated cardiomyopathy.
        J Am Coll Cardiol. 2016; 67: 2996-3010
        • Kabekkodu S.P.
        • Mananje S.R.
        • Saya R.P.
        A study on the role of heart type fatty acid binding protein in the diagnosis of acute myocardial infarction.
        J Clin Diagn Res. 2016; 10: OC07-OC10
        • Kakkar R.
        • Lee R.T.
        The IL-33/ST2 pathway: therapeutic target and novel biomarker.
        Nat Rev Drug Discov. 2008; 7: 827-840
        • Kempf T.
        • Sinning J.M.
        • Quint A.
        • Bickel C.
        • Sinning C.
        • Wild P.S.
        • et al.
        Growth-differentiation factor-15 for risk stratification in patients with stable and unstable coronary heart disease: results from the AtheroGene study.
        Circ Cardiovasc Genet. 2009; 2: 286-292
        • Kempf T.
        • Wollert K.C.
        Growth-differentiation factor-15 in heart failure.
        Heart Fail Clin. 2009; 5: 537-547
        • Mildner M.
        • Storka A.
        • Lichtenauer M.
        • Mlitz V.
        • Ghannadan M.
        • Hoetzenecker K.
        • et al.
        Primary sources and immunological prerequisites for sST2 secretion in humans.
        Cardiovasc Res. 2010; 87: 769-777
        • Miller A.M.
        • Liew F.Y.
        The IL-33/ST2 pathway–a new therapeutic target in cardiovascular disease.
        Pharmacol Ther. 2011; 131: 179-186
        • Mosterd A.
        • Hoes A.W.
        Clinical epidemiology of heart failure.
        Heart. 2007; 93: 1137-1146
        • Niizeki T.
        • Takeishi Y.
        • Arimoto T.
        • Takabatake N.
        • Nozaki N.
        • Hirono O.
        • et al.
        Heart-type fatty acid-binding protein is more sensitive than troponin T to detect the ongoing myocardial damage in chronic heart failure patients.
        J Card Fail. 2007; 13: 120-127
        • Pistulli R.
        • Konig S.
        • Drobnik S.
        • Kretzschmar D.
        • Rohm I.
        • Lichtenauer M.
        • et al.
        Decrease in dendritic cells in endomyocardial biopsies of human dilated cardiomyopathy.
        Eur J Heart Fail. 2013; 15: 974-985
        • Ponikowski P.
        • Voors A.A.
        • Anker S.D.
        • Bueno H.
        • Cleland J.G.
        • Coats A.J.
        • et al.
        2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
        Eur Heart J. 2016; 37: 2129-2200
        • Pouleur A.C.
        Which biomarkers do clinicians need for diagnosis and management of heart failure with reduced ejection fraction?.
        Clin Chim Acta. 2015; 443: 9-16
        • Reiter M.
        • Twerenbold R.
        • Reichlin T.
        • Mueller M.
        • Hoeller R.
        • Moehring B.
        • et al.
        Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction.
        Heart. 2013; 99: 708-714
        • Ruan L.B.
        • He L.
        • Zhao S.
        • Zhu P.
        • Li W.Y.
        Prognostic value of plasma heart-type fatty acid-binding protein in patients with acute pulmonary embolism: a meta-analysis.
        Chest. 2014; 146: 1462-1467
        • Schmieder A.
        • Multhoff G.
        • Radons J.
        Interleukin-33 acts as a pro-inflammatory cytokine and modulates its receptor gene expression in highly metastatic human pancreatic carcinoma cells.
        Cytokine. 2012; 60: 514-521
        • Schmitz J.
        • Owyang A.
        • Oldham E.
        • Song Y.
        • Murphy E.
        • McClanahan T.K.
        • et al.
        IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines.
        Immunity. 2005; 23: 479-490
        • Sehestedt T.
        • Lyngbaek S.
        • Eugen-Olsen J.
        • Jeppesen J.
        • Andersen O.
        • Hansen T.W.
        • et al.
        Soluble urokinase plasminogen activator receptor is associated with subclinical organ damage and cardiovascular events.
        Atherosclerosis. 2011; 216: 237-243
        • Thuno M.
        • Macho B.
        • Eugen-Olsen J.
        suPAR: the molecular crystal ball.
        Dis Markers. 2009; 27: 157-172
        • van Riet E.E.
        • Hoes A.W.
        • Wagenaar K.P.
        • Limburg A.
        • Landman M.A.
        • Rutten F.H.
        Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review.
        Eur J Heart Fail. 2016; 18: 242-252
        • Wach S.
        • Al-Janabi O.
        • Weigelt K.
        • Fischer K.
        • Greither T.
        • Marcou M.
        • et al.
        The combined serum levels of miR-375 and urokinase plasminogen activator receptor are suggested as diagnostic and prognostic biomarkers in prostate cancer.
        Int J Cancer. 2015; 137: 1406-1416
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • Butler J.
        • Casey Jr., D.E.
        • Colvin M.M.
        • et al.
        ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America Circulation 2017.
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • Butler J.
        • Casey Jr., D.E.
        • Drazner M.H.
        • et al.
        2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines.
        J Am Coll Cardiol. 2013; 62: e147-e239
        • Zeyda M.
        • Wernly B.
        • Demyanets S.
        • Kaun C.
        • Hammerle M.
        • Hantusch B.
        • et al.
        Severe obesity increases adipose tissue expression of interleukin-33 and its receptor ST2, both predominantly detectable in endothelial cells of human adipose tissue.
        Int J Obes (Lond). 2013; 37: 658-665