Multibiomarker analysis in patients with acute myocardial infarction
Corresponding Author
Christiana Schernthaner
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Correspondence to: Christiana Schernthaner, Department of Cardiology, Salzburger Landeskliniken, Paracelsus Medical University, Muellner Hauptstrasse 48, A-5020 Salzburg, Austria. Tel.: +43 (0) 5 7255 55880; fax: +43 (0) 5 7255 25788; e-mail: [email protected]Search for more papers by this authorMichael Lichtenauer
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorBernhard Wernly
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorVera Paar
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorRudin Pistulli
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorIlonka Rohm
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorChristian Jung
Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany
Search for more papers by this authorHans-Reiner Figulla
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorAttila Yilmaz
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorJanne Cadamuro
Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorElisabeth Haschke-Becher
Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorJohn Pernow
Division of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Schweden
Search for more papers by this authorPaul Christian Schulze
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorUta C. Hoppe
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorDaniel Kretzschmar
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorCorresponding Author
Christiana Schernthaner
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Correspondence to: Christiana Schernthaner, Department of Cardiology, Salzburger Landeskliniken, Paracelsus Medical University, Muellner Hauptstrasse 48, A-5020 Salzburg, Austria. Tel.: +43 (0) 5 7255 55880; fax: +43 (0) 5 7255 25788; e-mail: [email protected]Search for more papers by this authorMichael Lichtenauer
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorBernhard Wernly
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorVera Paar
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorRudin Pistulli
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorIlonka Rohm
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorChristian Jung
Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf, Germany
Search for more papers by this authorHans-Reiner Figulla
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorAttila Yilmaz
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorJanne Cadamuro
Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorElisabeth Haschke-Becher
Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorJohn Pernow
Division of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Schweden
Search for more papers by this authorPaul Christian Schulze
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorUta C. Hoppe
Department of Cardiology, Paracelsus Medical University, Salzburg, Austria
Search for more papers by this authorDaniel Kretzschmar
Division of Cardiology, Angiology, Pneumology and Intensive MedicalCare, Department of Internal Medicine I, Friedrich-Schiller-University Jena, Jena, Germany
Search for more papers by this authorAbstract
Background
Novel biomarkers representing different pathobiological pathways and their role in patients with acute myocardial infarction (AMI) were studied.
Methods
We retrospectively analysed serum levels of soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR), heart-type fatty acid-binding protein (H-FABP) and plasma fetuin A in blood of patients with AMI (STEMI, n = 61; NSTEMI, n = 57) compared to controls with excluded coronary artery disease (n = 76). Furthermore, detailed correlation analysis was performed.
Results
Compared with controls, in patients with STEMI and NSTEMI higher levels expressed as median of sST2 in pg/mL (STEMI: 13210·9, NSTEMI: 11989·1, control: 5248; P < 0·001), GDF-15 in pg/mL (STEMI: 818·8, NSTEMI 677·5, control 548·6; P < 0·001), suPAR in pg/mL (STEMI: 3461·1, NSTEMI: 3466·7, control: 2463·6; P < 0·001), H-FABP in ng/mL (STEMI: 5·8, NSTEMI: 5·4, control: 0·0; P < 0·001) and lower plasma fetuin A levels in μg/mL (STEMI: 95, NSTEMI: 54, control: 116·6; P < 0·001) were detected. Correlation analysis found clinical and biochemical parameters such as ejection fraction, length of hospital stay, creatine kinase, NT-proBNP and hs Troponin T levels as well as inflammatory markers (CRP, leucocytes) to be significantly correlated with novel biomarkers.
Conclusion
Plasma levels of novel biomarkers were significantly elevated (sST2, GDF-15, H-FABP, suPAR) or inversely downregulated (fetuin A) in patients with AMI compared to a control group with excluded coronary artery disease. Significant correlations with various clinical parameters and standard biochemical markers were found.
Supporting Information
| Filename | Description |
|---|---|
| eci12785-sup-0001-FigS1.pptxapplication/mspowerpoint, 140.9 KB | Figure S1. Serum concentrations of soluble suppression of tumorigenicity (sST2) in pg/mL, growth-differentiation factor-15 (GDF-15) in pg/mL, soluble urokinase plasminogen activator receptor (suPAR) in pg/mL, heart-type fatty acid-binding protein (H-FABP) in ng/mL at 0-2 hours and 72 hours post acute myocardial infarction (n = 20). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Christia P, Frangogiannis NG. Targeting inflammatory pathways in myocardial infarction. Eur J Clin Invest 2013; 43: 986–95.
- 2Feistritzer HJ, Klug G, Reinstadler SJ, Reindl M, Mayr A, Mair J et al. Novel biomarkers predicting cardiac function after acute myocardial infarction. Br Med Bull 2016; 119: 63–74.
- 3Bhardwaj A, Januzzi JL. ST2: a novel biomarker for heart failure. Expert Rev Mol Diagn 2010; 10: 459–64.
- 4Broch K, Andreassen AK, Ueland T, Michelsen AE, Stueflotten W, Aukrust P et al. Soluble ST2 reflects hemodynamic stress in non-ischemic heart failure. Int J Cardiol 2015; 179: 378–84.
- 5Shimpo M, Morrow DA, Weinberg EO, Sabatine MS, Murphy SA, Antman EM et al. Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction. Circulation 2004; 109: 2186–90.
- 6Kohli P, Bonaca MP, Kakkar R, Kudinova AY, Scirica BM, Sabatine MS et al. Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial. Clin Chem 2012; 58: 257–66.
- 7O'Donoghue ML, Morrow DA, Cannon CP, Jarolim P, Desai NR, Sherwood MW et al. Multimarker risk stratification in patients with acute myocardial infarction. J Am Heart Assoc 2016; 5: e002586.
- 8Tominaga S. A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor. FEBS Lett 1989; 258: 301–4.
- 9Werenskiold AK, Hoffmann S, Klemenz R. Induction of a mitogen-responsive gene after expression of the Ha-ras oncogene in NIH 3T3 fibroblasts. Mol Cell Biol 1989; 9: 5207–14.
- 10Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK 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: 479–90.
- 11Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J et al. The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ Res 2006; 98: 351–60.
- 12Wollert KC, Kempf T. Growth differentiation factor 15 in heart failure: an update. Curr Heart Fail Rep 2012; 9: 337–45.
- 13Lindahl B. The story of growth differentiation factor 15: another piece of the puzzle. Clin Chem 2013; 59: 1550–2.
- 14Schlittenhardt D, Schober A, Strelau J, Bonaterra GA, Schmiedt W, Unsicker K et al. Involvement of growth differentiation factor-15/macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in oxLDL-induced apoptosis of human macrophages in vitro and in arteriosclerotic lesions. Cell Tissue Res 2004; 318: 325–33.
- 15Wollert KC, Kempf T, Lagerqvist B, Lindahl B, Olofsson S, Allhoff T et al. Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome. Circulation 2007; 116: 1540–8.
- 16Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily. Proc Natl Acad Sci USA 1997; 94: 11514–9.
- 17Wollert KC, Kempf T, Peter T, Olofsson S, James S, Johnston N et al. Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome. Circulation 2007; 115: 962–71.
- 18Farhan S, Freynhofer MK, Brozovic I, Bruno V, Vogel B, Tentzeris I et al. Determinants of growth differentiation factor 15 in patients with stable and acute coronary artery disease. A prospective observational study. Cardiovasc Diabetol 2016; 15: 60.
- 19Damman P, Kempf T, Windhausen F, van Straalen JP, 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: 356–63.
- 20Nakata T, Hashimoto A, Hase M, Tsuchihashi K, Shimamoto K. Human heart-type fatty acid-binding protein as an early diagnostic and prognostic marker in acute coronary syndrome. Cardiology 2003; 99: 96–104.
- 21Hamza M, Demerdash S, Ibrahim M. Heart-type fatty acid-binding protein as a diagnostic biochemical marker for early detection of myocardial infarction. Acta Cardiol 2016; 71: 537–41.
- 22Niizeki T, Takeishi Y, Arimoto T, Nozaki N, Hirono O, Watanabe T et al. Persistently increased serum concentration of heart-type fatty acid-binding protein predicts adverse clinical outcomes in patients with chronic heart failure. Circ J 2008; 72: 109–14.
- 23Boscheri A, Wunderlich C, Langer M, Schoen S, Wiedemann B, Stolte D et al. Correlation of heart-type fatty acid-binding protein with mortality and echocardiographic data in patients with pulmonary embolism at intermediate risk. Am Heart J 2010; 160: 294–300.
- 24Huai Q, Mazar AP, Kuo A, Parry GC, Shaw DE, Callahan J et al. Structure of human urokinase plasminogen activator in complex with its receptor. Science 2006; 311: 656–9.
- 25Thunø M, Macho B, Eugen-Olsen J. suPAR: the molecular crystal ball. Dis Markers 2009; 27: 157–72.
- 26Eugen-Olsen J, Andersen O, Linneberg A, Ladelund S, Hansen TW, 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.
- 27Lyngbæk S, Marott JL, Møller DV, Christiansen M, Iversen KK, Clemmensen PM et al. Usefulness of soluble urokinase plasminogen activator receptor to predict repeat myocardial infarction and mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention. Am J Cardiol 2012; 110: 1756–63.
- 28Feistritzer HJ, Klug G, Reinstadler SJ, Gröber MT, Mair J, Kirchmair R, et al. Fetuin A is related to infarct size, left ventricular function and remodelling after acute STEMI. Open Heart 2015; 2: e000244.
- 29Lim P, Collet JP, Moutereau S, Guigui N, Mitchell-Heggs L, Loric S et al. Fetuin-A is an independent predictor of death after ST-elevation myocardial infarction. Clin Chem 2007; 53: 1835–40.
- 30Ix JH, Barrett-Connor E, Wassel CL, Cummins K, Bergstrom J, Daniels LB et al. The associations of fetuin-A with subclinical cardiovascular disease in community-dwelling persons: the Rancho Bernardo Study. J Am Coll Cardiol 2011; 58: 2372–9.
- 31Kretzschmar D, Betge S, Windisch A, Pistulli R, Rohm I, Fritzenwanger M et al. Recruitment of circulating dendritic cell precursors into the infracted myocardium and pro-inflammatory response in acute myocardial infarction. Clin Sci (Lond) 2012; 23: 387–98.
- 32Mueller T, Zimmermann M, Dieplinger B, Ankersmit HJ, Haltmayer M. Comparison of plasma concentrations of soluble ST2 measured by three different commercially available assays: the MBL ST2 assay, the Presage ST2 assay, and the R&D ST2 assay. Clin Chim Acta 2012; 413: 1493–4.
- 33Kakoti A, Goswami P. Heart type fatty acid binding protein: structure, function and biosensing applications for early detection of myocardial infarction. Biosens Bioelectron 2013; 43: 400–11.
- 34Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med 2007; 13: 1096–101.
- 35Cobos E, Jumper C, Lox C. Pretreatment determination of the serum urokinase plasminogen activator and its soluble receptor in advanced small-cell lung cancer or non-small-cell lung cancer. Clin Appl Thromb Hemost 2003; 9: 241–6.
- 36Simera I, Moher D, Hoey J, Schulz KF, Altman DG. A catalogue of reporting guidelines for health research. Eur J Clin Invest 2010; 40: 35–53.
- 37Mueller C, Giannitsis E, Christ M, Ordóñez-Llanos J, deFilippi C, McCord J et al. Multicenter evaluation of a 0-hour/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin T. Ann Emerg Med 2016; 68: 76–87.e4.
- 38Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009; 361: 858–67.
- 39Felker GM, Hasselblad V, Hernandez AF, O'Connor CM. Biomarker-guided therapy in chronic heart failure: a meta-analysis of randomized controlled trials. Am Heart J 2009; 158: 422–30.
- 40Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD et al. ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J 2012; 33: 2551–67.
- 41Roubille F, Samri A, Cornillet L, Sportouch-Dukhan C, Davy JM, Raczka F et al. Routinely-feasible multiple biomarkers score to predict prognosis after revascularized STEMI. Eur J Intern Med 2010; 21: 131–6.
- 42Sherwood MW, Morrow DA, Scirica BM, Jiang S, Bode C, Rifai N et al. Early dynamic risk stratification with baseline troponin levels and 90-minute ST-segment resolution to predict 30-day cardiovascular mortality in ST-segment elevation myocardial infarction:analysis from CLopidogrel as Adjunctive ReperfusIon TherapY (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28. Am Heart J 2010; 159: 964–71.e1.
- 43Lindahl B, Venge P, James S. The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes. Am Heart J 2010; 160: 224–9. Erratum in: Am Heart J 2011;161:425.
- 44Barbarash O, Gruzdeva O, Uchasova E, Dyleva Y, Belik E, Akbasheva O et al. Prognostic value of soluble ST2 during hospitalization for ST-segment elevation myocardial infarction. Ann Lab Med 2016; 36: 313–9.
- 45Ciccone MM, Cortese F, Gesualdo M, Riccardi R, Di Nunzio D, Moncelli M et al. A novel cardiac bio-marker: ST2: a review. Molecules 2013; 18: 15314–28.
- 46Koller L, Stojkovic S, Richter B, Sulzgruber P, Potolidis C, Liebhart F et al. Soluble urokinase-type plasminogen activator receptor improves risk prediction in patients with chronic heart failure. JACC Heart Fail 2017; 5: 268–77.
