Biomarkers for risk prediction in acute decompensated heart failure

Current Heart Failure Reports

Volumn 11, Issue 3, 2014, Pages 246-259

  Van Der Velde, A Rogier ^a   Meijers, Wouter C ^a   De Boer, Rudolf A ^a  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

Acute heart failure; Biomarker; BIVA; Cardiac remodeling; Copeptin; CRP; Fibrosis; Galectin 3; GDF 15; HE4; IL 6; MR proADM; Neuroendocrine activation; NGAL; NT proANP; NT proBNP; Procalcitonin; Prognosis; sST2; Syndecan 1; Troponin

Indexed keywords

BIOLOGICAL MARKER; C REACTIVE PROTEIN; CHROMOGRANIN A; COPEPTIN; CYSTATIN C; GALECTIN 3; GROWTH DIFFERENTIATION FACTOR 15; INTERLEUKIN 6; NATRIURETIC FACTOR; NATRIURETIC PEPTIDE TYPE C; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; PROADRENOMEDULLIN; PROCALCITONIN; SYNDECAN 1; TROPONIN;

ACUTE HEART FAILURE; CARDIOVASCULAR RISK; DISEASE MARKER; GOLD STANDARD; HUMAN; IMPEDANCE; INFLAMMATION; KIDNEY INJURY; MUSCLE CELL; PATHOPHYSIOLOGY; PREDICTIVE VALUE; PROGNOSIS; REVIEW; RISK ASSESSMENT; SEX DIFFERENCE; STRATIFICATION; TISSUE REGENERATION; ACUTE DISEASE; BLOOD; HEALTH; HEART FAILURE; HEART VENTRICLE REMODELING; INCIDENCE;

ACUTE DISEASE; BIOLOGICAL MARKERS; GLOBAL HEALTH; HEART FAILURE; HUMANS; INCIDENCE; PROGNOSIS; RISK ASSESSMENT; VENTRICULAR REMODELING;

EID: 84906043541     PISSN: 15469530     EISSN: 15469549     Source Type: Journal    
DOI: 10.1007/s11897-014-0207-7     Document Type: Review

References (153)

1. •• Follath F, Yilmaz MB, Delgado JF, et al. Clinical presentation, management and outcomes in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). Intensive Care Med. 2011;37:619-26. ALARM-HF was a large survey among 4,953 patients with AHF in nine different countries and described characteristics and management of acute heart failure in these patients.
2. Rudiger A, Harjola VP, Muller A, et al. Acute heart failure: clinical presentation, one-year mortality and prognostic factors. Eur J Heart Fail. 2005;7:662-70. (Pubitemid 40733001)
3. • Harjola VP, Follath F, Nieminen MS, et al. Characteristics, outcomes, and predictors of mortality at 3 months and 1 year in patients hospitalized for acute heart failure. Eur J Heart Fail. 2010;12:239-48. The EuroHeart Failure Survey (EHFS) II evaluated 3-month and 12-month mortality in 2,981 patients with acute heart failure from 30 different countries and identified clinical risk markers.
4. • Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89-95. The Biomarkers Definitions Working Group defined biomarkers as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention.
5. Lee CS, Tkacs NC. Current concepts of neurohormonal activation in heart failure:mediators andmechanisms.AACN Adv Crit Care. 2008;19:364-85. quiz 386-7.
6. Misra A, Mann DL. Treatment of heart failure beyond practice guidelines. Role of cardiac remodeling. Circ J. 2008;72(Suppl A):A1-7.
7. Jougasaki M, Burnett Jr JC. Adrenomedullin: potential in physiology and pathophysiology. Life Sci. 2000;66:855-72. (Pubitemid 30084473)
8. Sata M, Kakoki M, Nagata D, et al. Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a cyclic GMP-independent mechanism. Hypertension. 2000;36:83-8. (Pubitemid 30602157)
9. .• Lainchbury JG, Troughton RW, Lewis LK, Yandle TG, Richards AM, Nicholls MG. Hemodynamic, hormonal, and renal effects of short-term adrenomedullin infusion in healthy volunteers. J Clin Endocrinol Metab. 2000;85:1016-20. This article describes the hemodynamic effects of systemic infusion of adrenomedullin up to pathophysiological plasma levels in healthy volunteers. (Pubitemid 32269342)
10. Nicholls MG, Charles CJ, Lainchbury JG, et al. Adrenomedullin in heart failure. Hypertens Res. 2003;26(Suppl):S135-40. (Pubitemid 36372329)
11. Meeran K, O'Shea D, Upton PD, et al. Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study. J Clin Endocrinol Metab. 1997;82:95-100. (Pubitemid 27021277)
12. Morgenthaler NG, Struck J, Alonso C, Bergmann A. Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay. Clin Chem. 2005;51:1823-9. (Pubitemid 41368172)
13. Travaglino F, Russo V, De Berardinis B, et al. Thirty and ninety days mortality predictive value of admission and in-hospital procalcitonin and mid-regional pro-adrenomedullin testing in patients with dyspnea. Results from the VERyfing DYspnea trial. Am J Emerg Med. 2014;32:334-41.
14. Cinar O, Cevik E, Acar A, et al. Evaluation of mid-regional proatrial natriuretic peptide, procalcitonin, and mid-regional pro-adrenomedullin for the diagnosis and risk stratification of dyspneic ED patients. Am J Emerg Med. 2012;30:1915-20.
15. Shah RV, Truong QA, Gaggin HK, Pfannkuche J, Hartmann O, Januzzi Jr JL. Mid-regional pro-atrial natriuretic peptide and pro-adrenomedullin testing for the diagnostic and prognostic evaluation of patients with acute dyspnoea. Eur Heart J. 2012;33:2197-205.
16. .• Maisel A, Mueller C, Nowak RM, et al. Midregion prohormone adrenomedullin and prognosis in patients presenting with acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. J Am Coll Cardiol. 2011;58:1057-67. The BACH trial was a prospective, multicenter, international study of 1,641 ADHF patients presenting with dyspnea at the emergency department and studied the diagnostic and prognostic value of various biomarkers.
17. Peacock WF, Nowak R, Christenson R, et al. Short-term mortality risk in emergency department acute heart failure. Acad Emerg Med. 2011;18:947-58.
18. .• Chatterjee K. Neurohormonal activation in congestive heart failure and the role of vasopressin. Am J Cardiol. 2005;95:8B-13. This review focuses on the different components of neurohormonal activation in heart failure.
19. Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation. 1990;82:1724-9. (Pubitemid 20367975)
20. Stoiser B, Mortl D, Hulsmann M, et al. Copeptin, a fragment of the vasopressin precursor, as a novel predictor of outcome in heart failure. Eur J Clin Invest. 2006;36:771-8. (Pubitemid 44569965)
21. Morgenthaler NG, Struck J, Alonso C, Bergmann A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem. 2006;52:112-9. (Pubitemid 43032474)
22. Struck J, Morgenthaler NG, Bergmann A. Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients. Peptides. 2005;26:2500-4. (Pubitemid 41676723)
23. Meijer E, Bakker SJ, Halbesma N, de Jong PE, Struck J, Gansevoort RT. Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort. Kidney Int. 2010;77:29-36.
24. .• Gegenhuber A, Struck J, Dieplinger B, et al. Comparative evaluation of B-type natriuretic peptide, mid-regional pro-A-type natriuretic peptide, mid-regional pro-adrenomedullin, and Copeptin to predict 1-year mortality in patients with acute destabilized heart failure. J Card Fail. 2007;13:42-9. This study compares the prognostic value of different novel biomarkers and concludes some have similar predictive properties compared with BNP for 1-year all-cause mortality.
25. Neuhold S, Huelsmann M, Strunk G, et al. Prognostic value of emerging neurohormones in chronic heart failure during optimization of heart failure-specific therapy. Clin Chem. 2010;56:121-6.
26. .• Miller WL, Hartman KA, Grill DE, Struck J, Bergmann A, Jaffe AS. Serial measurements of midregion proANP and copeptin in ambulatory patients with heart failure: incremental prognostic value of novel biomarkers in heart failure. Heart. 2012;98:389-94. The authors studied serial monitoring of MR-proANP and copeptin and concluded this was useful for detecting the highest-risk outpatients with HF.
27. • Taupenot L, Harper KL, O 'Connor DT. The chromogranin- secretogranin family. N Engl J Med. 2003;348:1134-49. This is an extensive review about the functions and mechanisms of the chromogranin-secretogranin family.
28. Mazza R, Imbrogno S, Tota B. The interplay between chromogranin A-derived peptides and cardiac natriuretic peptides in cardioprotection against catecholamine-evoked stress. Regul Pept. 2010;165:86-94.
29. Pieroni M, Corti A, Tota B, et al. Myocardial production of chromogranin A in human heart: a new regulatory peptide of cardiac function. Eur Heart J. 2007;28:1117-27. (Pubitemid 47343865)
30. .• Dieplinger B, Gegenhuber A, Struck J, et al. Chromogranin A and C-terminal endothelin-1 precursor fragment add independent prognostic information to amino-terminal proBNP in patients with acute destabilized heart failure. Clin Chim Acta. 2009;400:91-6. In 137 patients with acute destabilized heart failure, increased chromogranin A and CT-proET-1 plasma concentrations add independent prognostic information to NT-proBNP.
31. Teiger E, Than VD, Richard L, et al. Apoptosis in pressure overload-induced heart hypertrophy in the rat. J Clin Invest. 1996;97:2891-7. (Pubitemid 26197104)
32. .•• Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis. Cell Mol Life Sci. 2014;71:549-74. This review discusses the molecular pathways that are involved in myocardial fibrosis.
33. Weinberg EO, Shimpo M, De Keulenaer GW, et al. Expression and regulation of ST2, an interleukin-1 receptor familymember, in cardiomyocytes andmyocardial infarction. Circulation. 2002;106:2961-6. (Pubitemid 35424749)
34. Shimpo M, Morrow DA,Weinberg EO, 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. (Pubitemid 38625395)
35. .•• Adams Jr KF, Fonarow GC, Emerman CL, et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005;149:209-16. The ADHERE registry describes characteristics and outcome of 100,000 patients hospitalized for acute decompensated heart failure.
36. Tago K, Noda T, Hayakawa M, et al. Tissue distribution and subcellular localization of a variant form of the human ST2 gene product, ST2V. Biochem Biophys Res Commun. 2001;285:1377-83. (Pubitemid 32912936)
37. Sanada S, Hakuno D, Higgins LJ, Schreiter ER, McKenzie AN, Lee RT. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest. 2007;117:1538-49. (Pubitemid 46871338)
38. Seki K, Sanada S, Kudinova AY, et al. Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail. 2009;2:684-91.
39. Januzzi Jr JL, Peacock WF, Maisel AS, et al. Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study. J Am Coll Cardiol. 2007;50:607-13. (Pubitemid 47199007)
40. Mueller T, Dieplinger B, Gegenhuber A, Poelz W, Pacher R, Haltmayer M. Increased plasma concentrations of soluble ST2 are predictive for 1-year mortality in patients with acute destabilized heart failure. Clin Chem. 2008;54:752-6. (Pubitemid 351573718)
41. .• Pascual-Figal DA, Manzano-Fernandez S, Boronat M, et al. Soluble ST2, high-sensitivity troponin T- and N-terminal pro-Btype natriuretic peptide: complementary role for risk stratification in acutely decompensated heart failure. Eur J Heart Fail. 2011;13: 718-25. This study investigated the use of ST2 and hs-Troponin and concluded these markers provide superior risk stratification over NT-proBNP.
42. Shah RV, Chen-Tournoux AA, Picard MH, van Kimmenade RR, Januzzi JL. Serum levels of the interleukin-1 receptor family member ST2, cardiac structure and function, and long-term mortality in patients with acute dyspnea. Circ Heart Fail. 2009;2:311-9.
43. Shah RV, Januzzi Jr JL. ST2: a novel remodeling biomarker in acute and chronic heart failure. Curr Heart Fail Rep. 2010;7:9-14.
44. Breidthardt T, Balmelli C, Twerenbold R, et al. Heart failure therapy-induced early ST2 changes may offer long-term therapy guidance. J Card Fail. 2013;19:821-8.
45. .• Gaggin HK, Szymonifka J, Bhardwaj A, et al. Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highly-sensitive troponin T measurements in patients with chronic heart failure. JACC Heart Fail. 2014;2:65-72. This article performed a head-to-head comparison of three promising biomarkers in chronic heart failure and concluded only serial ST2 measurements added prognostic information to baseline values.
46. Sharma UC, Pokharel S, van Brakel TJ, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004;110:3121-8. (Pubitemid 39492008)
47. .• de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ. Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail. 2009;11:811-7. This review describes the mechanisms of galectin-3 in development of heart failure.
48. • Calvier L, Miana M, Reboul P, et al. Galectin-3 mediates aldosterone-induced vascular fibrosis. Arterioscler Thromb Vasc Biol. 2013;33:67-75. The authors conclude that aldosterone might induce fibrosis via a galectin-3 dependent pathway.
49. Sasaki T, Brakebusch C, Engel J, Timpl R.Mac-2 binding protein is a cell-adhesive protein of the extracellular matrix which self-assembles into ring-like structures and binds beta1 integrins, collagens and fibronectin. EMBO J. 1998;17:1606-13. (Pubitemid 28119114)
50. Song L, Tang JW, Owusu L, Sun MZ, Wu J, Zhang J. Galectin-3 in cancer. Clin Chim Acta. 2014;431C:185-91.
51. Henderson NC, Sethi T. The regulation of inflammation by galectin-3. Immunol Rev. 2009;230:160-71.
52. Carrasco-Sanchez FJ, Aramburu-Bodas O, Salamanca-Bautista P, et al. Predictive value of serum galectin-3 levels in patients with acute heart failure with preserved ejection fraction. Int J Cardiol. 2013;169:177-82.
53. Meijers WC, Januzzi JL, de Filippi C, et al. Elevated plasma galectin-3 is associated with near-term rehospitalization in heart failure: a pooled analysis of 3 clinical trials. Am Heart J. 2014;167:853-60.
54. .• van Kimmenade RR, Januzzi Jr JL, Ellinor PT, et al. Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure. J Am Coll Cardiol. 2006;48:1217-24. This substudy of the PRIDE demonstrated the clinical utility of galectin-3 for the first time, showing that galectin-3 was the best predictor for 60-day mortality.
55. Eurlings LW, Sanders-van Wijk S, van Kimmenade R, et al. Multimarker strategy for short-term risk assessment in patients with dyspnea in the emergency department: the MARKED (Multi mARKer Emergency Dyspnea)-risk score. J Am Coll Cardiol. 2012;60:1668-77.
56. van der Velde AR, Gullestad L, Ueland T, et al. Prognostic value of changes in galectin-3 levels over time in patients with heart failure: data from CORONA and COACH. Circ Heart Fail. 2013;6:219-26.
57. .•• Yu L, Ruifrok WP, Meissner M, et al. Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis. Circ Heart Fail. 2013;6:107-17. This article showed that galectin-3 could also serve as a "target for therapy". Inhibition of galectin-3 resulted in attenuation of fibrosis in animal models of heart failure.
58. .• Xu J, Kimball TR, Lorenz JN, et al. GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation. Circ Res. 2006;98:342-50. The authors identified GDF-15 as a novel antagonist of hypertrophic response.
59. Kempf T, Eden M, Strelau J, et al. The transforming growth factor-beta superfamilymember growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ Res. 2006;98:351-60.
60. de Jager SC, Bermudez B, Bot I, et al. Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis. J Exp Med. 2011;208:217-25.
61. Kempf T, von Haehling S, Peter T, et al. Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol. 2007;50:1054-60. (Pubitemid 47348231)
62. Foley PW, Stegemann B, Ng K, et al. Growth differentiation factor-15 predicts mortality and morbidity after cardiac resynchronization therapy. Eur Heart J. 2009;30:2749-57.
63. Anand IS, Kempf T, Rector TS, et al. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial. Circulation. 2010;122:1387-95.
64. Lok DJ, Klip IT, Lok SI, et al. Incremental prognostic power of novel biomarkers (growth-differentiation factor-15, high-sensitivity C-reactive protein, galectin-3, and high-sensitivity troponin-T) in patients with advanced chronic heart failure. Am J Cardiol. 2013;112:831-7.
65. Izumiya Y, Hanatani S, Kimura Y, et al. Growth differentiation factor-15 is a useful prognostic marker in patients with heart failure with preserved ejection fraction. Can J Cardiol. 2014;30:338-44.
66. .•• Doust JA, Pietrzak E, Dobson A, Glasziou P. How well does Btype natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. BMJ. 2005;330:625. This systematic review concludes that BNP is a strong prognostic factor in patients with heart failure.
67. Brunner-La Rocca HP, Kaye DM, Woods RL, Hastings J, Esler MD. Effects of intravenous brain natriuretic peptide on regional sympathetic activity in patients with chronic heart failure as compared with healthy control subjects. J Am Coll Cardiol. 2001;37:1221-7.
68. Kimura K, Yamaguchi Y, Horii M, et al. ANP is cleared much faster than BNP in patients with congestive heart failure. Eur J Clin Pharmacol. 2007;63:699-702. (Pubitemid 46911345)
69. .• Moertl D, Berger R, Struck J, et al. Comparison of midregional pro-atrial and B-type natriuretic peptides in chronic heart failure: influencing factors, detection of left ventricular systolic dysfunction, and prediction of death. J Am Coll Cardiol. 2009;53:1783-90. MR-proANP was found to be a better predictor for death in patients with chronic heart failure, compared to BNP and NTproBNP.
70. Morgenthaler NG, Struck J, Thomas B, Bergmann A. Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma. Clin Chem. 2004;50:234-6. (Pubitemid 38125732)
71. Mueller T, Gegenhuber A, Poelz W, Haltmayer M. Diagnostic accuracy of B type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure. Heart. 2005;91:606-12. (Pubitemid 40559349)
72. Maisel A, Hollander JE, Guss D, et al. Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath. J Am Coll Cardiol. 2004;44:1328-33. (Pubitemid 39208893)
73. Baggish AL, van Kimmenade RR, Pinto Y, et al. New York Heart Association class versus amino-terminal pro-B type natriuretic peptide for acute heart failure prognosis. Biomarkers. 2010;15:307-14.
74. Bayes-Genis A, Santalo-Bel M, Zapico-Muniz E, et al. N-terminal probrain natriuretic peptide (NT-proBNP) in the emergency diagnosis and in-hospital monitoring of patients with dyspnoea and ventricular dysfunction. Eur J Heart Fail. 2004;6:301-8. (Pubitemid 38253049)
75. Bettencourt P, Azevedo A, Pimenta J, Frioes F, Ferreira S, Ferreira A. N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients. Circulation. 2004;110:2168-74. (Pubitemid 39372496)
76. Januzzi Jr JL, Rehman SU, Mohammed AA, et al. Use of aminoterminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction. J Am Coll Cardiol. 2011;58:1881-9.
77. .• Schou M, Gustafsson F, Videbaek L, et al. Adding serial N-terminal pro brain natriuretic peptide measurements to optimal clinical management in outpatients with systolic heart failure: a multicentre randomized clinical trial (NorthStar monitoring study). Eur J Heart Fail. 2013;15:818-27. When serial measurements of NT-proBNP were added to optimal clinical management, this was not associated with improved outcome.
78. Waldo SW, Beede J, Isakson S, et al. Pro-B-type natriuretic peptide levels in acute decompensated heart failure. J Am Coll Cardiol. 2008;51:1874-82. (Pubitemid 351615249)
79. Mueller C, Laule-Kilian K, Scholer A, et al. B-type natriuretic peptide for acute dyspnea in patients with kidney disease: insights from a randomized comparison. Kidney Int. 2005;67:278-84. (Pubitemid 40019250)
80. Das SR, Drazner MH, Dries DL, et al. Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation. 2005;112:2163-8. (Pubitemid 41475811)
81. .• O'Connor CM, Starling RC, Hernandez AF, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011;365:32-43. Infusion of nesiritide in a randomized controlled trial in 7,141 patients did not affect the rate of death or hospitalization.
82. .•• Seronde MF, Gayat E, Logeart D, et al. Comparison of the diagnostic and prognostic values of B-type and atrial-type natriuretic peptides in acute heart failure. Int J Cardiol. 2013;168:3404-11. This study of 710 patients evaluated the diagnostic and prognostic value of four natriuretic peptides and concluded that MR-proANP had the best prognostic value at five years.
83. Testa G, Della-Morte D, Cacciatore F, et al. Precipitating factors in younger and older adults with decompensated chronic heart failure: are they different? J Am Geriatr Soc. 2013;61:1827-8.
84. Steele IC, Nugent AM, Maguire S, et al. Cytokine profile in chronic cardiac failure. Eur J Clin Invest. 1996;26:1018-22. (Pubitemid 26386314)
85. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102:2165-8.
86. Du Clos TW, Mold C. C-reactive protein: an activator of innate immunity and a modulator of adaptive immunity. Immunol Res. 2004;30:261-77. (Pubitemid 39546229)
87. Zairis MN, Tsiaousis GZ, Georgilas AT, et al. Multimarker strategy for the prediction of 31 days cardiac death in patients with acutely decompensated chronic heart failure. Int J Cardiol. 2010;141:284-90.
88. Kalogeropoulos AP, Tang WH, Hsu A, et al. High sensitivity C-reactive protein in acute heart failure: insights from the ASCENDHF trial. J Card Fail. 2014;20:319-26.
89. .• Lourenco P, Paulo Araujo J, Paulo C, et al. Higher C-reactive protein predicts worse prognosis in acute heart failure only in noninfected patients. Clin Cardiol. 2010;33:708 -14. CRP has prognostic value in acute decompensated heart failure patients without infection but not in patients with infectious complications.
90. Delevaux I, Andre M, Colombier M, et al. Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes? Ann Rheum Dis. 2003;62:337-40. (Pubitemid 36363440)
91. Picariello C, Lazzeri C, Valente S, Chiostri M, Gensini GF. Procalcitonin in acute cardiac patients. Intern Emerg Med. 2011;6:245-52.
92. Picariello C, Lazzeri C, Valente S, Chiostri M, Attana P, Gensini GF. Kinetics of procalcitonin in cardiogenic shock and in septic shock. Preliminary data. Acute Card Care. 2010;12:96-101.
93. Sinning CR, Sinning JM, Schulz A, et al. Association of serum procalcitonin with cardiovascular prognosis in coronary artery disease. Circ J. 2011;75:1184-91.
94. Meisner M, Adina H, Schmidt J. Correlation of procalcitonin and C-reactive protein to inflammation, complications, and outcome during the intensive care unit course of multiple-trauma patients. Crit Care. 2006;10:R1.
95. .• Travaglino F, Russo V, De Berardinis B, et al. Thirty and ninety days mortality predictive value of admission and in-hospital procalcitonin and mid-regional pro-adrenomedullin testing in patients with dyspnea. Results from the VERyfing DYspnea trial. Am J Emerg Med. 2014;32:334-41. In patients with dyspnea, procalcitonin and MR-proADM improved risk stratification and management.
96. Naffaa M, Makhoul BF, Tobia A, et al. Procalcitonin and interleukin 6 for predicting blood culture positivity in sepsis. Am J Emerg Med. 2014;32:448-51.
97. Maisel A, Neath SX, Landsberg J, et al. Use of procalcitonin for the diagnosis of pneumonia in patients presenting with a chief complaint of dyspnoea: results from the BACH (Biomarkers in Acute Heart Failure) trial. Eur J Heart Fail. 2012;14:278-86.
98. Hausfater P, Garric S, Ayed SB, Rosenheim M, Bernard M, Riou B. Usefulness of procalcitonin as a marker of systemic infection in emergency department patients: a prospective study. Clin Infect Dis. 2002;34:895-901. (Pubitemid 34229756)
99. .• Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res. 2002;53:31-47. This review describes the different components of the inflammatory response following myocardial infarction. (Pubitemid 34020764)
100. Schuett H, Luchtefeld M, Grothusen C, Grote K, Schieffer B. How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb Haemost. 2009;102:215-22.
101. Rose-John S, Scheller J, Elson G, Jones SA. Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J Leukoc Biol. 2006;80:227-36. (Pubitemid 44835496)
102. Milo-Cotter O, Cotter-Davison B, Lombardi C, et al. Neurohormonal activation in acute heart failure: results from VERITAS. Cardiology. 2011;119:96-105.
103. Lassus JP, Harjola VP, Peuhkurinen K, et al. Cystatin C, NT-proBNP, and inflammatory markers in acute heart failure: insights into the cardiorenal syndrome. Biomarkers. 2011;16:302-10.
104. .• Miettinen KH, Lassus J, Harjola VP, et al. Prognostic role of pro-and anti-inflammatory cytokines and their polymorphisms in acute decompensated heart failure. Eur J Heart Fail. 2008;10:396-403. Proinflammatory and anti-inflammatory cytokines were measured in 423 patients with acute decompensated heart failure. IL-6, IL-10 and TNF-α provided important prognostic information in these patients.
105. Pudil R, Tichy M, Andrys C, et al. Plasma interleukin-6 level is associated with NT-proBNP level and predicts short- and long-term mortality in patients with acute heart failure. Acta Med (Hradec Kralove). 2010;53:225-8.
106. .• Mann DL, Bristow MR. Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation. 2005;111: 2837-49. This review describes heart failure in different clinical model systems, like a cardiorenal model, a hemodynamic model, and a neurohormonal model. (Pubitemid 40791557)
107. Agewall S, Giannitsis E, Jernberg T, Katus H. Troponin elevation in coronary vs. non-coronary disease. Eur Heart J. 2011;32:404-11.
108. Adams 3rd JE, Bodor GS, Davila-Roman VG, et al. Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation. 1993;88:101-6. (Pubitemid 23195438)
109. Gaze DC, Collinson PO. Multiple molecular forms of circulating cardiac troponin: analytical and clinical significance. Ann Clin Biochem. 2008;45:349-55. (Pubitemid 352031540)
110. Thygesen K, Alpert JS, White HD, et al. Universal definition of myocardial infarction. Circulation. 2007;116:2634-53. (Pubitemid 350182388)
111. Steen H, Giannitsis E, Futterer S,Merten C, Juenger C, Katus HA. Cardiac troponin T at 96 hours after acute myocardial infarction correlates with infarct size and cardiac function. J Am Coll Cardiol. 2006;48:2192-4. (Pubitemid 44855412)
112. Sato Y, Fujiwara H, Takatsu Y. Cardiac troponin and heart failure in the era of high-sensitivity assays. J Cardiol. 2012;60:160-7.
113. .•• Peacock 4th WF, De Marco T, Fonarow GC, et al. Cardiac troponin and outcome in acute heart failure. N Engl J Med. 2008;358: 2117-26. Troponin levels were measured in 84,872 patients who were hospitalized for acute decompensated heart failure. A positive troponin test was associated with higher in-hospital mortality.
114. .• de Antonio M, Lupon J, Galan A, et al. Head-to-head comparison of high-sensitivity troponin Tand sensitive-contemporary troponin I regarding heart failure risk stratification. Clin Chim Acta. 2013;426:18-24. In a head-to-head comparison between troponin Tand troponin I, troponin Tshowed better performance and was a better predictor for death.
115. Kuwabara Y, Sato Y, Miyamoto T, et al. Persistently increased serum concentrations of cardiac troponin in patients with acutely decompensated heart failure are predictive of adverse outcomes. Circ J. 2007;71:1047-51. (Pubitemid 46998018)
116. Damman K, Jaarsma T, Voors AA, et al. Both in- and out-hospital worsening of renal function predict outcome in patients with heart failure: results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH). Eur J Heart Fail. 2009;11:847-54.
117. .• Damman K, Navis G, Voors AA, et al. Worsening renal function and prognosis in heart failure: systematic review and meta-analysis. J Card Fail. 2007;13:599-608. This systematic review and meta-analysis concludes that worsening renal function predicts substantially higher rates of mortality and hospitalization in patients with heart failure. (Pubitemid 47513536)
118. Sarraf M,Masoumi A, Schrier RW. Cardiorenal syndrome in acute decompensated heart failure. Clin J Am Soc Nephrol. 2009;4:2013-26.
119. Laterza OF, Price CP, Scott MG. Cystatin C: an improved estimator of glomerular filtration rate? Clin Chem. 2002;48:699-707. (Pubitemid 34439101)
120. Fliser D, Ritz E. Serum cystatin C concentration as a marker of renal dysfunction in the elderly. Am J Kidney Dis. 2001;37:79-83. (Pubitemid 32055022)
121. Manzano-Fernandez S, Boronat-Garcia M, Albaladejo-Oton MD, et al. Complementary prognostic value of cystatin C, N-terminal pro-B-type natriuretic Peptide and cardiac troponin T in patients with acute heart failure. Am J Cardiol. 2009;103:1753-9.
122. Lassus J, Harjola VP, Sund R, et al. Prognostic value of cystatin C in acute heart failure in relation to other markers of renal function and NT-proBNP. Eur Heart J. 2007;28:1841-7. (Pubitemid 47236639)
123. .• Maisel AS, Mueller C, Fitzgerald R, et al. Prognostic utility of plasma neutrophil gelatinase-associated lipocalin in patients with acute heart failure: the NGAL EvaLuation Along with B-type NaTriuretic Peptide in acutely decompensated heart failure (GALLANT) trial. Eur J Heart Fail. 2011;13:846-51. In this study, NGAL was measured in 186 patients with acute decompensated heart failure. Plasma NGAL was found to be a strong predictor for 30-days outcome and improved reclassification over BNP.
124. Aghel A, Shrestha K, Mullens W, Borowski A, Tang WH. Serum neutrophil gelatinase-associated lipocalin (NGAL) in predicting worsening renal function in acute decompensated heart failure. J Card Fail. 2010;16:49-54.
125. .•• Lassus J, Gayat E, Mueller C, et al. Incremental value of biomarkers to clinical variables for mortality prediction in acutely decompensated heart failure: the Multinational Observational Cohort on Acute Heart Failure (MOCA) study. Int J Cardiol. 2013;168:2186-94. In the MOCA study, 5,306 patients with acute decompensated heart failure were included. Biomarkers including sST2,MR-proADM, natriuretic peptides and CRP added prognostic value to clinical risk factors for predicting mortality.
126. .• Zairis MN, Tsiaousis GZ, Georgilas AT, et al. Multimarker strategy for the prediction of 31 days cardiac death in patients with acutely decompensated chronic heart failure. Int J Cardiol. 2010;141:284-90. This multimarker study concluded that an increasing number of elevated biomarkers increased the risk of cardiac death gradually.
127. Potocki M, Breidthardt T, Mueller A, et al. Copeptin and risk stratification in patients with acute dyspnea. Crit Care. 2010;14:R213.
128. Boffa GM, Zaninotto M, Sartor R, et al. Interleukin-6 and tumor necrosis factor-alpha as biochemical markers of heart failure: a head-to-head clinical comparison with B-type natriuretic peptide. J Cardiovasc Med (Hagerstown). 2009;10:758-64.
129. Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett Jr JC. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol. 2002;40:976-82. (Pubitemid 34994995)
130. Hong M, Yan Q, Tao B, et al. Estradiol, progesterone and testosterone exposures affect the atrial natriuretic peptide gene expression in vivo in rats. Biol Chem Hoppe Seyler. 1992;373:213-8.
131. Deng Y, Kaufman S. The influence of reproductive hormones on ANF release by rat atria. Life Sci. 1993;53:689-96.
132. Ho JE, Gona P, Pencina MJ, et al. Discriminating clinical features of heart failure with preserved vs. reduced ejection fraction in the community. Eur Heart J. 2012;33:1734-41.
133. .• Meyer S, van der Meer P, van Deursen VM, et al. Neurohormonal and clinical sex differences in heart failure. Eur Heart J. 2013;34:2538-47. Female patients presenting with heart failure have a different clinical presentation and better outcome compared to male patients.
134. .• de Boer RA, van Veldhuisen DJ, Gansevoort RT, et al. The fibrosis marker galectin-3 and outcome in the general population. J Intern Med. 2012;272:55- 64. In this large community based cohort, galectin-3 was found to be associated with age and various risk factors of cardiovascular disease, with a strong gender interaction.
135. Coglianese EE, Larson MG, Vasan RS, et al. Distribution and clinical correlates of the interleukin receptor family member soluble ST2 in the Framingham Heart Study. Clin Chem. 2012;58:1673-81.
136. Melander O, Maisel AS, Almgren P, et al. Plasma proneurotensin and incidence of diabetes, cardiovascular disease, breast cancer, and mortality. JAMA. 2012;308:1469-75.
137. Montagnana M, Danese E, Giudici S, et al. HE4 in ovarian cancer: from discovery to clinical application. Adv Clin Chem. 2011;55:1-20.
138. .• de Boer RA, Cao Q, Postmus D, et al. The WAP four-disulfide core domain protein HE4: a novel biomarker for heart failure. JACC Heart Fail. 2013;1:164-9. In the COACH trial, HE4 improved net reclassification when it was added to the clinical model and was correlated with markers of heart failure severity.
139. .•• LeBleu VS, Teng Y, O'Connell JT, et al. Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis. Nat Med. 2013;19:227-31. HE4 was found to be a new potential biomarker of (renal) fibrosis and could serve as a new therapeutic target.
140. Smith GL, Lichtman JH, Bracken MB, et al. Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol. 2006;47:1987-96.
141. Del Ry S, Passino C, Maltinti M, Emdin M, Giannessi D. C-type natriuretic peptide plasma levels increase in patients with chronic heart failure as a function of clinical severity. Eur J Heart Fail. 2005;7:1145-8. (Pubitemid 41721117)
142. Wu C, Wu F, Pan J, Morser J, Wu Q. Furin-mediated processing of Pro-C-type natriuretic peptide. J Biol Chem. 2003;278:25847-52. (Pubitemid 36835344)
143. .• Zakeri R, Sangaralingham SJ, Sandberg SM, Heublein DM, Scott CG, Burnett Jr JC. Urinary C-type natriuretic peptide: a new heart failure biomarker. JACC Heart Fail. 2013;1:170-7. Urinary Ctype natriuretic peptide was detected in patients with heart failure and may have clinical utility as a biomarker.
144. • Tromp J, van der Pol A, Klip IT, et al. The Fibrosis Marker Syndecan-1 and Outcome in Heart Failure Patients with Reduced and Preserved Ejection Fraction. Circ Heart Fail. 2014;7:457-62. Syndecan-1 levels correlate with biomarkers of fibrosis and was a predictor for outcome in patients with HFpEF but not in HFrEF.
145. Castillo-Martinez L, Colin-Ramirez E, Orea-Tejeda A, et al. Cachexia assessed by bioimpedance vector analysis as a prognostic indicator in chronic stable heart failure patients. Nutrition. 2012;28:886-91.
146. Di Somma S, Navarin S, Giordano S, et al. The emerging role of biomarkers and bio-impedance in evaluating hydration status in patients with acute heart failure. Clin Chem Lab Med. 2012;50:2093-105.
147. .• Di Somma S, Lalle I, Magrini L, et al. Additive diagnostic and prognostic value of Bioelectrical Impedance Vector Analysis (BIVA) to brain natriuretic peptide 'grey-zone' in patients with acute heart failure in the emergency department. Eur Heart J Acute Cardiovasc Care. 2014;3:167-75. In 270 patients with acute heart failure, Bioelectrical Impedance Vector Analysis provided additive 30-day prognostic value to BNP.
148. Morrow DA, de Lemos JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation. 2007;115:949-52. (Pubitemid 46328287)
149. van Kimmenade RR, Januzzi Jr JL. Emerging biomarkers in heart failure. Clin Chem. 2012;58:127-38.
150. Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006;355:2631-9. (Pubitemid 44969122)
151. .• Cohen Freue GV, Meredith A, Smith D, et al. Computational biomarker pipeline from discovery to clinical implementation: plasma proteomic biomarkers for cardiac transplantation. PLoS Comput Biol. 2013;9:e1002963. Quantitive proteomics has led to discovery of new biomarkers for various diseases, thus, providing new treatments and diagnostics. This proposed computational pipeline is applicable to other biomarker proteomic studies.
152. Scrutinio D, Ammirati E, Guida P, et al. Clinical utility of N-terminal pro-B-type natriuretic peptide for risk stratification of patients with acute decompensated heart failure. Derivation and validation of the ADHF/NT-proBNP risk score. Int J Cardiol. 2013;168:2120-6.
153. Maisel A, Xue Y, Shah K, et al. Increased 90-day mortality in patients with acute heart failure with elevated copeptin: secondary results fromthe Biomarkers in Acute Heart Failure (BACH) study. Circ Heart Fail. 2011;4:613-20.