Heart Failure Reviews

, Volume 15, Issue 4, pp 251–273

Biomarkers in heart failure: a clinical review

  • J. Paul Rocchiccioli
  • John J. V. McMurray
  • Anna F. Dominiczak
Article
  • 301 Downloads

Abstract

The diagnosis and management of heart failure remains challenging despite considerable clinical advances in recent decades. With greater understanding of the pathophysiology of this complex syndrome, a large number of candidate biomarkers have emerged and duly received scientific and clinical attention. These are frequently a measure of the degree of pathophysiological derangement or counter-regulatory processes occurring in heart failure and include biomarkers of neurohormonal activation, myocyte necrosis and myocardial remodelling amongst others. As such they may serve as an indicator of the presence, severity and possibly therapeutic response of the heart failure syndrome and may complement conventional clinical measurements and acumen. This may in turn lead to tangible clinical benefits and the targeting of intensified and often costly therapies to those most at risk. This article reviews and summarises the most extensively investigated biomarkers currently available, with an emphasis on clinical applicability and discusses the future evaluation of candidate biomarkers in patients with heart failure.

Keywords

Heart failure Biomarkers Neurohormones Remodelling Diagnosis Risk stratification 

References

  1. 1.
    Stewart S, MacIntyre K, Capewell S, McMurray JJ (2003) Heart failure and the aging population: an increasing burden in the 21st century? Heart 89(1):49–53PubMedCrossRefGoogle Scholar
  2. 2.
    Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, Tavazzi L, Smiseth OA, Gavazzi A, Haverich A, Hoes A, Jaarsma T, Korewicki J, Levy S, Linde C, Lopez-Sendon JL, Nieminen MS, Pierard L, WJ Remme (2005) Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): the task force for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology. Eur Heart J 26(11):1115–1140PubMedCrossRefGoogle Scholar
  3. 3.
    Thomas JT, Kelly RF, Thomas SJ, Stamos TD, Albasha K, Parrillo JE, Calvin JE (2002) Utility of history, physical examination, electrocardiogram, and chest radiograph for differentiating normal from decreased systolic function in patients with heart failure. Am J Med 112(6):437–445PubMedCrossRefGoogle Scholar
  4. 4.
    Fung ET, Wright GL Jr, Dalmasso EA (2000) Proteomic strategies for biomarker identification: progress and challenges. Curr Opin Mol Ther 2(6):643–650PubMedGoogle Scholar
  5. 5.
    Mann DL, Bristow MR (2005) Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation 111(21):2837–2849PubMedCrossRefGoogle Scholar
  6. 6.
    de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H (1981) A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 28(1):89–94PubMedCrossRefGoogle Scholar
  7. 7.
    Mukoyama M, Nakao K, Hosoda K, Suga S, Saito Y, Ogawa Y, Shirakami G, Jougasaki M, Obata K, Yasue H et al (1991) Brain natriuretic peptide as a novel cardiac hormone in humans. evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. J Clin Invest 87(4):1402–1412PubMedCrossRefGoogle Scholar
  8. 8.
    Vanderheyden M, Bartunek J, Goethals M (2004) Brain and other natriuretic peptides: molecular aspects. Eur J Heart Fail 6(3):261–268PubMedCrossRefGoogle Scholar
  9. 9.
    Vasan RS (2004) Expanding indications for natriuretic peptides: importance of better new (research) protocols. Am Heart J 148(5):743–746PubMedCrossRefGoogle Scholar
  10. 10.
    Omland T, Aakvaag A, Bonarjee VV, Caidahl K, Lie RT, Nilsen DW, Sundsfjord JA, Dickstein K (1996) Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction comparison with plasma atrial natriuretic peptide and n-terminal proatrial natriuretic peptide. Circulation 93(11):1963–1969PubMedGoogle Scholar
  11. 11.
    Tsutamoto T, Wada A, Maeda K, Hisanaga T, Mabuchi N, Hayashi M, Ohnishi M, Sawaki M, Fujii M, Horie H, Sugimoto Y, Kinoshita M (1999) Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction comparison with plasma angiotensin II and endothelin-1. Eur Heart J 20(24):1799–1807PubMedCrossRefGoogle Scholar
  12. 12.
    Petrie MC, Hillier C, Johnston F, McMurray JJ (2001) Effect of neutral endopeptidase inhibition on the actions of adrenomedullin and endothelin-1 in resistance arteries from patients with chronic heart failure. Hypertension 38(3):412–416PubMedGoogle Scholar
  13. 13.
    Lainchbury JG, Campbell E, Frampton CM, Yandle TG, Nicholls MG, Richards AM (2003) Brain natriuretic peptide and N-terminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath. J Am Coll Cardiol 42(4):728–735PubMedCrossRefGoogle Scholar
  14. 14.
    Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr (2002) Plasma brain natriuretic peptide concentration: impact of age and sex. J Am Coll Cardiol 40:976–982PubMedCrossRefGoogle Scholar
  15. 15.
    Bayes-Genis A, Lloyd-Jones DM, van Kimmenade RR, Lainchbury JG, Richards AM, Ordonez-Llanos J, Santalo M, Pinto YM, Januzzi JL Jr (2007) Effect of body mass index on diagnostic and prognostic usefulness of amino-terminal pro-brain natriuretic peptide in patients with acute dyspnea. Arch Intern Med 167(4):400–407PubMedCrossRefGoogle Scholar
  16. 16.
    McCullough PA, Sandberg KR (2003) B-type natriuretic peptide and renal disease. Heart Fail Rev 8(4):355–358PubMedCrossRefGoogle Scholar
  17. 17.
    Anwaruddin S, Lloyd-Jones DM, Baggish A, Chen A, Krauser D, Tung R, Chae C, Januzzi JL Jr (2006) Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study. J Am Coll Cardiol 47(1):91–97PubMedCrossRefGoogle Scholar
  18. 18.
    Schou M, Gustafsson F, Nielsen PH, Madsen LH, Kjaer A, Hildebrandt PR (2007) Unexplained week-to-week variation in BNP and NT-proBNP is low in chronic heart failure patients during steady state. Eur J Heart Fail 9(1):68–74PubMedCrossRefGoogle Scholar
  19. 19.
    Wu AH (2006) Serial testing of B-type natriuretic peptide and NTpro-BNP for monitoring therapy of heart failure: the role of biologic variation in the interpretation of results. Am Heart J 152(5):828–834PubMedCrossRefGoogle Scholar
  20. 20.
    Schou M, Gustafsson F, Kjaer A, Hildebrandt PR (2007) Long-term clinical variation of NT-proBNP in stable chronic heart failure patients. Eur Heart J 28(2):177–182PubMedCrossRefGoogle Scholar
  21. 21.
    Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B (2005) ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society. Circulation 112(12):e154–e235Google Scholar
  22. 22.
    Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT (2005) Does this dyspneic patient in the emergency department have congestive heart failure? JAMA 294(15):1944–1956PubMedCrossRefGoogle Scholar
  23. 23.
    Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA (2002) Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347(3):161–167PubMedCrossRefGoogle Scholar
  24. 24.
    Januzzi JL Jr, Camargo CA, Anwaruddin S, Baggish AL, Chen AA, Krauser DG, Tung R, Cameron R, Nagurney JT, Chae CU, Lloyd-Jones DM, Brown DF, Foran-Melanson S, Sluss PM, Lee-Lewandrowski E, Lewandrowski KB (2005) The N-terminal Pro-BNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study. Am J Cardiol 95(8):948–954PubMedCrossRefGoogle Scholar
  25. 25.
    Baggish AL, Siebert U, Lainchbury JG, Cameron R, Anwaruddin S, Chen A, Krauser DG, Tung R, Brown DF, Richards AM, Januzzi JL Jr (2006) A validated clinical and biochemical score for the diagnosis of acute heart failure: the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) acute heart failure score. Am Heart J 151(1):48–54PubMedCrossRefGoogle Scholar
  26. 26.
    Mueller T, Gegenhuber A, Poelz W, Haltmayer M (2005) Diagnostic accuracy of B type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure. Heart 91(5):606–612PubMedCrossRefGoogle Scholar
  27. 27.
    British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group (2003) British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 58(6):470–483CrossRefGoogle Scholar
  28. 28.
    Zaphiriou A, Robb S, Murray-Thomas T, Mendez G, Fox K, McDonagh T, Hardman SM, Dargie HJ, Cowie MR (2005) The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study. Eur J Heart Fail 7(4):537–541PubMedCrossRefGoogle Scholar
  29. 29.
    Cowie MR, Struthers AD, Wood DA, Coats AJ, Thompson SG, Poole-Wilson PA, Sutton GC (1997) Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet 350(9088):1349–1353PubMedCrossRefGoogle Scholar
  30. 30.
    Wright SP, Doughty RN, Pearl A, Gamble GD, Whalley GA, Walsh HJ, Gordon G, Bagg W, Oxenham H, Yandle T, Richards M, Sharpe N (2003) Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure diagnosis in primary care: a randomized, controlled trial. J Am Coll Cardiol 42(10):1793–1800PubMedCrossRefGoogle Scholar
  31. 31.
    Craig J, Bradbury I, Cummins E, Downe S, Foster L, Stout A (2005) The use of B-type naturetic peptides (BNP and NT-proBNP) in the investigation of patients with suspected heart failure. 2005 ed. Glasgow: NHS Quality Improvement Scotland; 2005 (Health Technology Assessment Report 6)Google Scholar
  32. 32.
    Scottish Intercollegiate Guidelines Network. Management of chronic heart failure. A national clinical guideline. Edinburgh: SIGN; 2007. Report No.: (SIGN Guideline no 95). Available from url: http://www.sign.ac.uk
  33. 33.
    Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS (2004) Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 350(7):655–663PubMedCrossRefGoogle Scholar
  34. 34.
    Vasan RS, Benjamin EJ, Larson MG, Leip EP, Wang TJ, Wilson PW, Levy D (2002) Plasma natriuretic peptides for community screening for left ventricular hypertrophy and systolic dysfunction: the Framingham Heart Study. JAMA 288(10):1252–1259PubMedCrossRefGoogle Scholar
  35. 35.
    Costello-Boerrigter LC, Boerrigter G, Redfield MM, Rodeheffer RJ, Urban LH, Mahoney DW, Jacobsen SJ, Heublein DM, Burnett JC Jr (2006) Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction. J Am Coll Cardiol 47(2):345–353PubMedCrossRefGoogle Scholar
  36. 36.
    McDonagh TA, Holmer S, Raymond I, Luchner A, Hildebrant P, Dargie HJ (2004) NT-proBNP and the diagnosis of heart failure: a pooled analysis of three European epidemiological studies. Eur J Heart Fail 6(3):269–273PubMedCrossRefGoogle Scholar
  37. 37.
    Jourdain P, Funck F, Bellorini M, Guillard N, Loiret J, Thebault B, Desnos M, Duboc D (2003) Bedside B-type natriuretic peptide and functional capacity in chronic heart failure. Eur J Heart Fail 5(2):155–160PubMedCrossRefGoogle Scholar
  38. 38.
    Berger R, Stanek B, Frey B, Sturm B, Huelsmann M, Bergler-Klein J, Pacher R (2001) B-type natriuretic peptides (BNP and PRO-BNP) predict longterm survival in patients with advanced heart failure treated with atenolol. J Heart Lung Transplant 20(2):251PubMedCrossRefGoogle Scholar
  39. 39.
    Cheng V, Kazanagra R, Garcia A, Lenert L, Krishnaswamy P, Gardetto N, Clopton P, Maisel A (2001) A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study. J Am Coll Cardiol 37(2):386–391PubMedCrossRefGoogle Scholar
  40. 40.
    Fisher C, Berry C, Blue L, Morton JJ, McMurray J (2003) N-terminal pro B type natriuretic peptide, but not the new putative cardiac hormone relaxin, predicts prognosis in patients with chronic heart failure. Heart 89(8):879–881PubMedCrossRefGoogle Scholar
  41. 41.
    Harrison A, Morrison LK, Krishnaswamy P, Kazanegra R, Clopton P, Dao Q, Hlavin P, Maisel AS (2002) B-type natriuretic peptide predicts future cardiac events in patients presenting to the emergency department with dyspnea. Ann Emerg Med 39(2):131–138PubMedCrossRefGoogle Scholar
  42. 42.
    Doust JA, Pietrzak E, Dobson A, Glasziou P (2005) How well does b-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. BMJ 330(7492):625PubMedCrossRefGoogle Scholar
  43. 43.
    Anand IS, Fisher LD, Chiang YT, Latini R, Masson S, Maggioni AP, Glazer RD, Tognoni G, Cohn JN (2003) Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation 107(9):1278–1283PubMedCrossRefGoogle Scholar
  44. 44.
    Hartmann F, Packer M, Coats AJ, Fowler MB, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Anker SD, Amann-Zalan I, Hoersch S, Katus HA (2004) Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Circulation 110(13):1780–1786PubMedCrossRefGoogle Scholar
  45. 45.
    Maisel A, Hollander JE, Guss D, McCullough P, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R (2004) 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 44(6):1328–1333PubMedCrossRefGoogle Scholar
  46. 46.
    Logeart D, Thabut G, Jourdain P, Chavelas C, Beyne P, Beauvais F, Bouvier E, Solal AC (2004) Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure. J Am Coll Cardiol 43(4):635–641PubMedCrossRefGoogle Scholar
  47. 47.
    Dahle TG, Miller LW (2005) Using changes in B-type naturetic peptide levels between hospital admission and discharge to predict mortality of patients with heart failure. J Am Coll Cardiol 45:138AGoogle Scholar
  48. 48.
    Verdiani V, Nozzoli C, Bacci F, Cecchin A, Rutili MS, Paladini S, Olivotto I (2005) Pre-discharge B-type natriuretic peptide predicts early recurrence of decompensated heart failure in patients admitted to a general medical unit. Eur J Heart Fail 7(4):566–571PubMedCrossRefGoogle Scholar
  49. 49.
    Gardner RS, Chong V, Morton I, McDonagh TA (2005) N-terminal brain natriuretic peptide is a more powerful predictor of mortality than endothelin-1, adrenomedullin and tumour necrosis factor-alpha in patients referred for consideration of cardiac transplantation. Eur J Heart Fail 7(2):253–260PubMedCrossRefGoogle Scholar
  50. 50.
    Gardner RS, Ozalp F, Murday AJ, Robb SD, McDonagh TA (2003) N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure. Eur Heart J 24(19):1735–1743PubMedCrossRefGoogle Scholar
  51. 51.
    Gardner RS, Chong KS, Morton JJ, McDonagh TA (2007) A change in N-terminal pro-brain natriuretic peptide is predictive of outcome in patients with advanced heart failure. Eur J Heart Fail 9(3):266–271PubMedCrossRefGoogle Scholar
  52. 52.
    Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-Solal A, Dietz R, Gavazzi A, van Gilst WH, Hobbs R, Korewicki J, Madeira HC, Moiseyev VS, Preda I, Widimsky J, Freemantle N, Eastaugh J, Mason J (2003) The EuroHeart Failure Survey Programme—a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J 24(5):464–474PubMedCrossRefGoogle Scholar
  53. 53.
    Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki M, Fujii M, Matsumoto T, Matsui T, Kinoshita M (2001) Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol 37(5):1228–1233PubMedCrossRefGoogle Scholar
  54. 54.
    Richards AM, Doughty R, Nicholls MG, MacMahon S, Ikram H, Sharpe N, Espiner EA, Frampton C, Yandle TG (1999) Neurohumoral prediction of benefit from carvedilol in ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. Circulation 99(6):786–792PubMedGoogle Scholar
  55. 55.
    Yoshimura M, Mizuno Y, Nakayama M, Sakamoto T, Sugiyama S, Kawano H, Soejima H, Hirai N, Saito Y, Nakao K, Yasue H, Ogawa H (2002) B-type natriuretic peptide as a marker of the effects of enalapril in patients with heart failure. Am J Med 112(9):716–720PubMedCrossRefGoogle Scholar
  56. 56.
    Fung JW, Yu CM, Yip G, Chan S, Yandle TG, Richards AM, Nicholls MG, Sanderson JE (2003) Effect of beta blockade (carvedilol or metoprolol) on activation of the renin-angiotensin-aldosterone system and natriuretic peptides in chronic heart failure. Am J Cardiol 92(4):406–410PubMedCrossRefGoogle Scholar
  57. 57.
    Murdoch DR, McDonagh TA, Byrne J, Blue L, Farmer R, Morton JJ, Dargie HJ (1999) Titration of vasodilator therapy in chronic heart failure according to plasma brain natriuretic peptide concentration: randomized comparison of the hemodynamic and neuroendocrine effects of tailored versus empirical therapy. Am Heart J 138(6 Pt 1):1126–1132PubMedCrossRefGoogle Scholar
  58. 58.
    Richards AM, Doughty R, Nicholls MG, MacMahon S, Sharpe N, Murphy J, Espiner EA, Frampton C, Yandle TG (2001) Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. J Am Coll Cardiol 37(7):1781–1787PubMedCrossRefGoogle Scholar
  59. 59.
    Berger R, Huelsman M, Strecker K, Bojic A, Moser P, Stanek B, Pacher R (2002) B-type natriuretic peptide predicts sudden death in patients with chronic heart failure. Circulation 105(20):2392–2397PubMedCrossRefGoogle Scholar
  60. 60.
    Klingenberg R, Zugck C, Becker R, Schellberg D, Heinze G, Kell R, Remppis A, Schoels W, Katus HA, Dengler TJ (2006) Raised B-type natriuretic peptide predicts implantable cardioverter-defibrillator therapy in patients with ischaemic cardiomyopathy. Heart 92(9):1323–1324PubMedCrossRefGoogle Scholar
  61. 61.
    Sinha AM, Filzmaier K, Breithardt OA, Kunz D, Graf J, Markus KU, Hanrath P, Stellbrink C (2003) Usefulness of brain natriuretic peptide release as a surrogate marker of the efficacy of long-term cardiac resynchronization therapy in patients with heart failure. Am J Cardiol 91(6):755–758PubMedCrossRefGoogle Scholar
  62. 62.
    Molhoek SG, Bax JJ, van Erven L, Bootsma M, Steendijk P, Lentjes E, Boersma E, van der Laarse A, van der Wall EE, Schalij MJ (2004) Atrial and brain natriuretic peptides as markers of response to resynchronisation therapy. Heart 90(1):97–98PubMedCrossRefGoogle Scholar
  63. 63.
    Yu CM, Fung JW, Zhang Q, Chan CK, Chan I, Chan YS, Kong SL, Sanderson JE, Lam CW (2005) Improvement of serum NT-proBNP predicts improvement in cardiac function and favorable prognosis after cardiac resynchronization therapy for heart failure. J Card Fail 11(5 Suppl):S42–S46PubMedCrossRefGoogle Scholar
  64. 64.
    Fruhwald FM, Fahrleitner-Pammer A, Berger R, Leyva F, Freemantle N, Erdmann E, Gras D, Kappenberger L, Tavazzi L, Daubert JC, Cleland JG (2007) Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony. Eur Heart J 28(13):1592–1597PubMedCrossRefGoogle Scholar
  65. 65.
    Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM (2000) Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 355(9210):1126–1130PubMedCrossRefGoogle Scholar
  66. 66.
    Jourdain P, Jondeau G, Funck F, Gueffet P, Le Helloco A, Donal E, Aupetit JF, Aumont MC, Galinier M, Eicher JC, Cohen-Solal A, Juilliere Y (2007) Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP Multicenter Study. J Am Coll Cardiol 49(16):1733–1739PubMedCrossRefGoogle Scholar
  67. 67.
    Lainchbury JG, Troughton RW, Frampton CM, Yandle TG, Hamid A, Nicholls MG, Richards AM (2006) NTproBNP-guided drug treatment for chronic heart failure: design and methods in the “BATTLESCARRED” trial. Eur J Heart Fail 8(5):532–538PubMedCrossRefGoogle Scholar
  68. 68.
    Brunner-La Rocca HP, Buser PT, Schindler R, Bernheim A, Rickenbacher P, Pfisterer M (2006) Management of elderly patients with congestive heart failure—design of the Trial of Intensified versus standard Medical Therapy in Elderly patients with Congestive Heart Failure (TIME-CHF). Am Heart J 151(5):949–955PubMedCrossRefGoogle Scholar
  69. 69.
    Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T (1984) Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 311(13):819–823PubMedGoogle Scholar
  70. 70.
    Benedict CR, Shelton B, Johnstone DE, Francis G, Greenberg B, Konstam M, Probstfield JL, Yusuf S (1996) Prognostic significance of plasma norepinephrine in patients with asymptomatic left ventricular dysfunction. SOLVD investigators. Circulation 94(4):690–697PubMedGoogle Scholar
  71. 71.
    Givertz MM, Braunwald E (2004) Neurohormones in heart failure: predicting outcomes, optimizing care. Eur Heart J 25(4):281–282PubMedCrossRefGoogle Scholar
  72. 72.
    Dzau VJ, Packer M, Lilly LS, Swartz SL, Hollenberg NK, Williams GH (1984) Prostaglandins in severe congestive heart failure. Relation to activation of the renin–angiotensin system and hyponatremia. N Engl J Med 310(6):347–352PubMedGoogle Scholar
  73. 73.
    Lilly LS, Dzau VJ, Williams GH, Rydstedt L, Hollenberg NK (1984) Hyponatremia in congestive heart failure: implications for neurohumoral activation and responses to orthostasis. J Clin Endocrinol Metab 59(5):924–930PubMedCrossRefGoogle Scholar
  74. 74.
    Lee WH, Packer M (1986) Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation 73(2):257–267PubMedGoogle Scholar
  75. 75.
    Levine TB, Franciosa JA, Vrobel T, Cohn JN (1982) Hyponatraemia as a marker for high renin heart failure. Br Heart J 47(2):161–166PubMedCrossRefGoogle Scholar
  76. 76.
    Pulignano G, Del Sindaco D, Tavazzi L, Lucci D, Gorini M, Leggio F, Porcu M, Scherillo M, Opasich C, Di Lenarda A, Senni M, Maggioni AP (2002) Clinical features and outcomes of elderly outpatients with heart failure followed up in hospital cardiology units: data from a large nationwide cardiology database (IN-CHF registry). Am Heart J 143(1):45–55PubMedCrossRefGoogle Scholar
  77. 77.
    Klein L, O’Connor CM, Leimberger JD, Gattis-Stough W, Pina IL, Felker GM, Adams KF Jr, Califf RM, Gheorghiade M (2005) Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study. Circulation 111(19):2454–2460PubMedCrossRefGoogle Scholar
  78. 78.
    Rohde LE, Goldraich L, Polanczyk CA, Borges AP, Biolo A, Rabelo E, Beck-Da-Silva L, Clausell N (2006) A simple clinically based predictive rule for heart failure in-hospital mortality. J Card Fail 12(8):587–593PubMedCrossRefGoogle Scholar
  79. 79.
    Wei CM, Lerman A, Rodeheffer RJ, McGregor CG, Brandt RR, Wright S, Heublein DM, Kao PC, Edwards WD, Burnett JC Jr (1994) Endothelin in human congestive heart failure. Circulation 89(4):1580–1586PubMedGoogle Scholar
  80. 80.
    Krum H, Goldsmith R, Wilshire-Clement M, Miller M, Packer M (1995) Role of endothelin in the exercise intolerance of chronic heart failure. Am J Cardiol 75(17):1282–1283PubMedCrossRefGoogle Scholar
  81. 81.
    Pousset F, Isnard R, Lechat P, Kalotka H, Carayon A, Maistre G, Escolano S, Thomas D, Komajda M (1997) Prognostic value of plasma endothelin-1 in patients with chronic heart failure. Eur Heart J 18(2):254–258PubMedGoogle Scholar
  82. 82.
    Masson S, Latini R, Anand IS, Barlera S, Judd D, Salio M, Perticone F, Perini G, Tognoni G, Cohn JN (2006) The prognostic value of big endothelin-1 in more than 2, 300 patients with heart failure enrolled in the Valsartan Heart Failure Trial (Val-HeFT). J Card Fail 12(5):375–380PubMedCrossRefGoogle Scholar
  83. 83.
    Selvais PL, Robert A, Ahn S, van Linden F, Ketelslegers JM, Pouleur H, Rousseau MF (2000) Direct comparison between endothelin-1, N-terminal proatrial natriuretic factor, and brain natriuretic peptide as prognostic markers of survival in congestive heart failure. J Card Fail 6(3):201–207PubMedCrossRefGoogle Scholar
  84. 84.
    Bunton DC, Petrie MC, Hillier C, Johnston F, McMurray JJ (2004) The clinical relevance of adrenomedullin: a promising profile? Pharmacol Ther 103(3):179–201PubMedCrossRefGoogle Scholar
  85. 85.
    Pousset F, Masson F, Chavirovskaia O, Isnard R, Carayon A, Golmard JL, Lechat P, Thomas D, Komajda M (2000) Plasma adrenomedullin, a new independent predictor of prognosis in patients with chronic heart failure. Eur Heart J 21(12):1009–1014PubMedCrossRefGoogle Scholar
  86. 86.
    Richards AM, Nicholls MG, Yandle TG, Frampton C, Espiner EA, Turner JG, Buttimore RC, Lainchbury JG, Elliott JM, Ikram H, Crozier IG, Smyth DW (1998) Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. Circulation 97(19):1921–1929PubMedGoogle Scholar
  87. 87.
    Nishikimi T, Miyata A, Horio T, Yoshihara F, Nagaya N, Takishita S, Yutani C, Matsuo H, Matsuoka H, Kangawa K (2000) Urocortin, a member of the corticotropin-releasing factor family, in normal and diseased heart. Am J Physiol Heart Circ Physiol 279(6):H3031–H3039PubMedGoogle Scholar
  88. 88.
    Ng LL, Loke IW, O’Brien RJ, Squire IB, Davies JE (2004) Plasma urocortin in human systolic heart failure. Clin Sci (Lond) 106(4):383–388CrossRefGoogle Scholar
  89. 89.
    Goetze JP, Rehfeld JF, Carlsen J, Videbaek R, Andersen CB, Boesgaard S, Friis-Hansen L (2006) Apelin: a new plasma marker of cardiopulmonary disease. Regul Pept 133(1–3):134–138PubMedCrossRefGoogle Scholar
  90. 90.
    Chong KS, Gardner RS, Morton JJ, Ashley EA, McDonagh TA (2006) Plasma concentrations of the novel peptide apelin are decreased in patients with chronic heart failure. Eur J Heart Fail 8(4):355–360PubMedCrossRefGoogle Scholar
  91. 91.
    Chen MM, Ashley EA, Deng DX, Tsalenko A, Deng A, Tabibiazar R, Ben Dor A, Fenster B, Yang E, King JY, Fowler M, Robbins R, Johnson FL, Bruhn L, McDonagh T, Dargie H, Yakhini Z, Tsao PS, Quertermous T (2003) Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Circulation 108(12):1432–1439PubMedCrossRefGoogle Scholar
  92. 92.
    Mann DL (1999) Mechanisms and models in heart failure: a combinatorial approach. Circulation 100(9):999–1008PubMedGoogle Scholar
  93. 93.
    Anwaruddin S, Askari AT, Topol EJ (2007) Redefining risk in acute coronary syndromes using molecular medicine. J Am Coll Cardiol 49(3):279–289PubMedCrossRefGoogle Scholar
  94. 94.
    Aviles RJ, Askari AT, Lindahl B, Wallentin L, Jia G, Ohman EM, Mahaffey KW, Newby LK, Califf RM, Simoons ML, Topol EJ, Berger P, Lauer MS (2002) Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction. N Engl J Med 346(26):2047–2052PubMedCrossRefGoogle Scholar
  95. 95.
    Sato Y, Yamada T, Taniguchi R, Nagai K, Makiyama T, Okada H, Kataoka K, Ito H, Matsumori A, Sasayama S, Takatsu Y (2001) Persistently increased serum concentrations of cardiac troponin t in patients with idiopathic dilated cardiomyopathy are predictive of adverse outcomes. Circulation 103(3):369–374PubMedGoogle Scholar
  96. 96.
    Horwich TB, Patel J, MacLellan WR, Fonarow GC (2003) Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 108(7):833–838PubMedCrossRefGoogle Scholar
  97. 97.
    Del Carlo CH, Pereira-Barretto AC, Cassaro-Strunz C, Latorre MdoR, Ramires JA (2004) Serial measure of cardiac troponin T levels for prediction of clinical events in decompensated heart failure. J Card Fail 10(1):43–48PubMedCrossRefGoogle Scholar
  98. 98.
    Hudson MP, O’Connor CM, Gattis WA, Tasissa G, Hasselblad V, Holleman CM, Gaulden LH, Sedor F, Ohman EM (2004) Implications of elevated cardiac troponin T in ambulatory patients with heart failure: a prospective analysis. Am Heart J 147(3):546–552PubMedCrossRefGoogle Scholar
  99. 99.
    Latini R, Masson S, Anand IS, Missov E, Carlson M, Vago T, Angelici L, Barlera S, Parrinello G, Maggioni AP, Tognoni G, Cohn JN (2007) Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation 116(11):1242–1249PubMedCrossRefGoogle Scholar
  100. 100.
    Ishii J, Cui W, Kitagawa F, Kuno T, Nakamura Y, Naruse H, Mori Y, Ishikawa T, Nagamura Y, Kondo T, Oshima H, Nomura M, Ezaki K, Hishida H (2003) Prognostic value of combination of cardiac troponin T and B-type natriuretic peptide after initiation of treatment in patients with chronic heart failure. Clin Chem 49(12):2020–2026PubMedCrossRefGoogle Scholar
  101. 101.
    Perna ER, Macin SM, Cimbaro Canella JP, Szyszko A, Franciosi V, Vargas , Morales W, Bayol AP, Kriskovich JO, Medina F, Gonzalez AB, Brizuela M (2006) Importance of early combined N-terminal pro-brain natriuretic peptide and cardiac troponin T measurements for long-term risk stratification of patients with decompensated heart failure. J Heart Lung Transplant 25(10):1230–1240PubMedCrossRefGoogle Scholar
  102. 102.
    Sakhuja R, Green S, Oestreicher EM, Sluss PM, Lee-Lewandrowski E, Lewandrowski KB, Januzzi JL Jr (2007) Amino-terminal pro-brain natriuretic peptide, brain natriuretic peptide, and troponin T for prediction of mortality in acute heart failure. Clin Chem 53(3):412–420PubMedCrossRefGoogle Scholar
  103. 103.
    Hansen MS, Stanton EB, Gawad Y, Packer M, Pitt B, Swedberg K, Rouleau JL (2002) Relation of circulating cardiac myosin light chain 1 isoform in stable severe congestive heart failure to survival and treatment with flosequinan. Am J Cardiol 90(9):969–973PubMedCrossRefGoogle Scholar
  104. 104.
    Sugiura T, Takase H, Toriyama T, Goto T, Ueda R, Dohi Y (2005) Circulating levels of myocardial proteins predict future deterioration of congestive heart failure. J Card Fail 11(7):504–509PubMedCrossRefGoogle Scholar
  105. 105.
    Schaap FG, van der Vusse GJ, Glatz JF (1998) Fatty acid-binding proteins in the heart. Mol Cell Biochem 180(1–2):43–51PubMedCrossRefGoogle Scholar
  106. 106.
    Setsuta K, Seino Y, Ogawa T, Arao M, Miyatake Y, Takano T (2002) Use of cytosolic and myofibril markers in the detection of ongoing myocardial damage in patients with chronic heart failure. Am J Med 113(9):717–722PubMedCrossRefGoogle Scholar
  107. 107.
    Niizeki T, Takeishi Y, Arimoto T, Takahashi T, Okuyama H, Takabatake N, Nozaki N, Hirono O, Tsunoda Y, Shishido T, Takahashi H, Koyama Y, Fukao A, Kubota I (2005) Combination of heart-type fatty acid binding protein and brain natriuretic peptide can reliably risk stratify patients hospitalized for chronic heart failure. Circ J 69(8):922–927PubMedCrossRefGoogle Scholar
  108. 108.
    Niizeki T, Takeishi Y, Arimoto T, Takabatake N, Nozaki N, Hirono O, Watanabe T, Nitobe J, Harada M, Suzuki S, Koyama Y, Kitahara T, Sasaki T, Kubota I (2007) 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 13(2):120–127PubMedCrossRefGoogle Scholar
  109. 109.
    Deschamps AM, Spinale FG (2006) Pathways of matrix metalloproteinase induction in heart failure: bioactive molecules and transcriptional regulation. Cardiovasc Res 69(3):666–676PubMedCrossRefGoogle Scholar
  110. 110.
    Sundstrom J, Evans JC, Benjamin EJ, Levy D, Larson MG, Sawyer DB, Siwik DA, Colucci WS, Sutherland P, Wilson PW, Vasan RS (2004) Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study. Circulation 109(23):2850–2856PubMedCrossRefGoogle Scholar
  111. 111.
    Rossi A, Cicoira M, Golia G, Zanolla L, Franceschini L, Marino P, Graziani M, Zardini P (2004) Amino-terminal propeptide of type III procollagen is associated with restrictive mitral filling pattern in patients with dilated cardiomyopathy: a possible link between diastolic dysfunction and prognosis. Heart 90(6):650–654PubMedCrossRefGoogle Scholar
  112. 112.
    Mizon-Gerard F, de Groote P, Lamblin N, Hermant X, Dallongeville J, Amouyel P, Bauters C, Helbecque N (2004) Prognostic impact of matrix metalloproteinase gene polymorphisms in patients with heart failure according to the aetiology of left ventricular systolic dysfunction. Eur Heart J 25(8):688–693PubMedCrossRefGoogle Scholar
  113. 113.
    Sundstrom J, Evans JC, Benjamin EJ, Levy D, Larson MG, Sawyer DB, Siwik DA, Colucci WS, Wilson PW, Vasan RS (2004) Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham Heart Study. Eur Heart J 25(17):1509–1516PubMedCrossRefGoogle Scholar
  114. 114.
    Kelly D, Cockerill G, Ng LL, Thompson M, Khan S, Samani NJ, Squire IB (2007) Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study. Eur Heart J 28(6):711–718PubMedCrossRefGoogle Scholar
  115. 115.
    Anker SD, von Haehling S (2004) Inflammatory mediators in chronic heart failure: an overview. Heart 90(4):464–470PubMedCrossRefGoogle Scholar
  116. 116.
    Vasan RS, Sullivan LM, Roubenoff R, Dinarello CA, Harris T, Benjamin EJ, Sawyer DB, Levy D, Wilson PW, D’Agostino RB (2003) Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study. Circulation 107(11):1486–1491PubMedCrossRefGoogle Scholar
  117. 117.
    Levine B, Kalman J, Mayer L, Fillit HM, Packer M (1990) Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 323(4):236–241PubMedCrossRefGoogle Scholar
  118. 118.
    Cicoira M, Bolger AP, Doehner W, Rauchhaus M, Davos C, Sharma R, Al Nasser FO, Coats AJ, Anker SD (2001) High tumour necrosis factor-alpha levels are associated with exercise intolerance and neurohormonal activation in chronic heart failure patients. Cytokine 15(2):80–86PubMedCrossRefGoogle Scholar
  119. 119.
    Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL (2001) Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone Trial (VEST). Circulation 103(16):2055–2059PubMedGoogle Scholar
  120. 120.
    Gwechenberger M, Hulsmann M, Berger R, Graf S, Springer C, Stanek B, Pacher R (2004) Interleukin-6 and B-type natriuretic peptide are independent predictors for worsening of heart failure in patients with progressive congestive heart failure. J Heart Lung Transplant 23(7):839–844PubMedCrossRefGoogle Scholar
  121. 121.
    Kell R, Haunstetter A, Dengler TJ, Zugck C, Kubler W, Haass M (2002) Do cytokines enable risk stratification to be improved in NYHA functional class III patients? Comparison with other potential predictors of prognosis. Eur Heart J 23(1):70–78PubMedCrossRefGoogle Scholar
  122. 122.
    Maeda K, Tsutamoto T, Wada A, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki M, Fujii M, Matsumoto T, Kinoshita M (2000) High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure. J Am Coll Cardiol 36(5):1587–1593PubMedCrossRefGoogle Scholar
  123. 123.
    Tsutamoto T, Hisanaga T, Fukai D, Wada A, Maeda Y, Maeda K, Kinoshita M (1995) Prognostic value of plasma soluble intercellular adhesion molecule-1 and endothelin-1 concentration in patients with chronic congestive heart failure. Am J Cardiol 76(11):803–808PubMedCrossRefGoogle Scholar
  124. 124.
    Yin WH, Chen JW, Young MS, Lin SJ (2007) Increased endothelial monocyte adhesiveness is related to clinical outcomes in chronic heart failure. Int J Cardiol 121(3):276–283PubMedCrossRefGoogle Scholar
  125. 125.
    Rivera M, Talens-Visconti R, Sirera R, Bertomeu V, Salvador A, Cortes R, Garcia de Burgos F, Climent V, Paya R, Martinez-Dolz L, Sancho-Tello MJ, Gonzalez-Molina A (2004) Soluble TNF-alpha and interleukin-6 receptors in the urine of heart failure patients their clinical value and relationship with plasma levels. Eur J Heart Fail 6(7):877–882PubMedGoogle Scholar
  126. 126.
    Weinberg EO, Shimpo M, Hurwitz S, Tominaga S, Rouleau JL, Lee RT (2003) Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation 107(5):721–726PubMedCrossRefGoogle Scholar
  127. 127.
    Stumpf C, Lehner C, Eskafi S, Raaz D, Yilmaz A, Ropers S, Schmeisser A, Ludwig J, Daniel WG, Garlichs CD (2003) Enhanced levels of CD154 (CD40 ligand) on platelets in patients with chronic heart failure. Eur J Heart Fail 5(5):629–637PubMedCrossRefGoogle Scholar
  128. 128.
    Ingelsson E, Arnlov J, Sundstrom J, Lind L (2005) Inflammation, as measured by the erythrocyte sedimentation rate, is an independent predictor for the development of heart failure. J Am Coll Cardiol 45(11):1802–1806PubMedCrossRefGoogle Scholar
  129. 129.
    Suleiman M, Khatib R, Agmon Y, Mahamid R, Boulos M, Kapeliovich M, Levy Y, Beyar R, Markiewicz W, Hammerman H, Aronson D (2006) Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C-reactive protein. J Am Coll Cardiol 47(5):962–968PubMedCrossRefGoogle Scholar
  130. 130.
    Yin WH, Chen JW, Jen HL, Chiang MC, Huang WP, Feng AN, Young MS, Lin SJ (2004) Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure. Am Heart J 147(5):931–938PubMedCrossRefGoogle Scholar
  131. 131.
    Anand IS, Latini R, Florea VG, Kuskowski MA, Rector T, Masson S, Signorini S, Mocarelli P, Hester A, Glazer R, Cohn JN (2005) C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation 112(10):1428–1434PubMedCrossRefGoogle Scholar
  132. 132.
    Ruilope LM, Van Veldhuisen DJ, Ritz E, Luscher TF (2001) Renal function: the Cinderella of cardiovascular risk profile. J Am Coll Cardiol 38:1782–1787PubMedCrossRefGoogle Scholar
  133. 133.
    Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, Granger CB, Michelson EL, Ostergren J, Cornel JH, de Zeeuw D, Pocock S, van Veldhuisen DJ (2006) Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 113(5):671–678PubMedCrossRefGoogle Scholar
  134. 134.
    Smilde TF, Hillege HL, Voors AA, Dunselman PH, van Veldhuisen DJ (2004) Prognostic importance of renal function in patients with early heart failure and mild left ventricular dysfunction. Am J Cardiol 94:240–243PubMedCrossRefGoogle Scholar
  135. 135.
    National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39:S1–266CrossRefGoogle Scholar
  136. 136.
    Kazama JJ, Kutsuwada K, Ataka K, Maruyama H, Gejyo F (2002) Serum cystatin C reliably detects renal dysfunction in patients with various renal diseases. Nephron 91(1):13–20PubMedCrossRefGoogle Scholar
  137. 137.
    Koenig W, Twardella D, Brenner H, Rothenbacher D (2005) Plasma concentrations of cystatin C in patients with coronary heart disease and risk for secondary cardiovascular events: more than simply a marker of glomerular filtration rate. Clin Chem 51(2):321–327PubMedCrossRefGoogle Scholar
  138. 138.
    Arimoto T, Takeishi Y, Niizeki T, Takabatake N, Okuyama H, Fukui A, Tachibana H, Nozaki N, Hirono O, Tsunoda Y, Miyashita T, Shishido T, Takahashi H, Koyama Y, Kubota I (2005) Cystatin C, a novel measure of renal function, is an independent predictor of cardiac events in patients with heart failure. J Card Fail 11(8):595–601PubMedCrossRefGoogle Scholar
  139. 139.
    Ix JH, Shlipak MG, Chertow GM, Whooley MA (2007) Association of cystatin C with mortality, cardiovascular events, and incident heart failure among persons with coronary heart disease: data from the Heart and Soul Study. Circulation 115(2):173–179PubMedCrossRefGoogle Scholar
  140. 140.
    Lassus J, Harjola VP, Sund R, Siirila-Waris K, Melin J, Peuhkurinen K, Pulkki K, Nieminen MS (2007) Prognostic value of cystatin C in acute heart failure in relation to other markers of renal function and NT-proBNP. Eur Heart J 28(15):1841–1847PubMedCrossRefGoogle Scholar
  141. 141.
    Katz SD (2004) Mechanisms and treatment of anemia in chronic heart failure. Congest Heart Fail 10:243–247PubMedCrossRefGoogle Scholar
  142. 142.
    Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Borenstein J (2002) Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure. J Am Coll Cardiol 39(11):1780–1786PubMedCrossRefGoogle Scholar
  143. 143.
    Ezekowitz JA, McAlister FA, Armstrong PW (2003) Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12065 patients with new-onset heart failure. Circulation 107(2):223–225PubMedCrossRefGoogle Scholar
  144. 144.
    Kosiborod M, Curtis JP, Wang Y, Smith GL, Masoudi FA, Foody JM, Havranek EP, Krumholz HM (2005) Anemia and outcomes in patients with heart failure: a study from the National Heart Care Project. Arch Intern Med 165(19):2237–2244PubMedCrossRefGoogle Scholar
  145. 145.
    Maggioni AP, Opasich C, Anand I, Barlera S, Carbonieri E, Gonzini L, Tavazzi L, Latini R, Cohn J (2005) Anemia in patients with heart failure: prevalence and prognostic role in a controlled trial and in clinical practice. J Card Fail 11(2):91–98PubMedCrossRefGoogle Scholar
  146. 146.
    Mozaffarian D, Nye R, Levy WC (2003) Anemia predicts mortality in severe heart failure: the prospective randomized amlodipine survival evaluation (PRAISE). J Am Coll Cardiol 41(11):1933–1939PubMedCrossRefGoogle Scholar
  147. 147.
    Berry C, Norrie J, Hogg K, Brett M, Stevenson K, McMurray JJ (2006) The prevalence, nature, and importance of hematologic abnormalities in heart failure. Am Heart J 151(6):1313–1321PubMedCrossRefGoogle Scholar
  148. 148.
    Van Veldhuisen DJ, McMurray JJ (2007) Are erythropoietin stimulating proteins safe and efficacious in heart failure? Why we need an adequately powered randomised outcome trial. Eur J Heart Fail 9(2):110–112PubMedCrossRefGoogle Scholar
  149. 149.
    Androne AS, Katz SD, Lund L, LaManca J, Hudaihed A, Hryniewicz K, Mancini DM (2003) Hemodilution is common in patients with advanced heart failure. Circulation 107(2):226–229PubMedCrossRefGoogle Scholar
  150. 150.
    Al Ahmad A, Rand WM, Manjunath G, Konstam MA, Salem DN, Levey AS, Sarnak MJ (2001) Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol 38(4):955–962PubMedCrossRefGoogle Scholar
  151. 151.
    Sharma R, Francis DP, Pitt B, Poole-Wilson PA, Coats AJ, Anker SD (2004) Haemoglobin predicts survival in patients with chronic heart failure: a substudy of the ELITE II trial. Eur Heart J 25(12):1021–1028PubMedCrossRefGoogle Scholar
  152. 152.
    Anand I, McMurray JJ, Whitmore J, Warren M, Pham A, McCamish MA, Burton PB (2004) Anemia and its relationship to clinical outcome in heart failure. Circulation 110(2):149–154PubMedCrossRefGoogle Scholar
  153. 153.
    Anand IS, Kuskowski MA, Rector TS, Florea VG, Glazer RD, Hester A, Chiang YT, Aknay N, Maggioni AP, Opasich C, Latini R, Cohn JN (2005) Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT. Circulation 112(8):1121–1127PubMedCrossRefGoogle Scholar
  154. 154.
    Komajda M, Anker SD, Charlesworth A, Okonko D, Metra M, Di Lenarda A, Remme W, Moullet C, Swedberg K, Cleland JG, Poole-Wilson PA (2006) The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J 27(12):1440–1446PubMedCrossRefGoogle Scholar
  155. 155.
    O’Meara E, Clayton T, McEntegart MB, McMurray JJ, Lang CC, Roger SD, Young JB, Solomon SD, Granger CB, Ostergren J, Olofsson B, Michelson EL, Pocock S, Yusuf S, Swedberg K, Pfeffer MA (2006) Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) program. Circulation 113(7):986–994PubMedCrossRefGoogle Scholar
  156. 156.
    Lauer MS, Evans JC, Levy D (1992) Prognostic implications of subclinical left ventricular dilatation and systolic dysfunction in men free of overt cardiovascular disease (the Framingham Heart Study). Am J Cardiol 70(13):1180–1184PubMedCrossRefGoogle Scholar
  157. 157.
    Gardner RS, Chong KS, Morton JJ, McDonagh TA (2005) N-terminal brain natriuretic peptide, but not anemia, is a powerful predictor of mortality in advanced heart failure. J Card Fail 11(5 Suppl):S47–S53PubMedCrossRefGoogle Scholar
  158. 158.
    Wu AH, Omland T, Wold Knudsen C, McCord J, Nowak RM, Hollander JE, Duc P, Storrow AB, Abraham WT, Clopton P, Maisel AS, McCullough PA (2005) Relationship of B-type natriuretic peptide and anemia in patients with and without heart failure: a substudy from the breathing not properly (BNP) multinational study. Am J Hematol 80(3):174–180PubMedCrossRefGoogle Scholar
  159. 159.
    Baggish AL, van Kimmenade R, Bayes-Genis A, Davis M, Lainchbury JG, Frampton C, Pinto Y, Richards MA, Januzzi JL (2007) Hemoglobin and N-terminal pro-brain natriuretic peptide: independent and synergistic predictors of mortality in patients with acute heart failure results from the International Collaborative of NT-proBNP (ICON) Study. Clin Chim Acta 381(2):145–150PubMedCrossRefGoogle Scholar
  160. 160.
    Ozkalemkas F, Ali R, Ozkocaman V, Ozcelik T, Ozan U, Ozturk H, Kurt E, Evrensel T, Yerci O, Tunali A (2005) The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: a clinical study of 19 cases. BMC Cancer 5:144PubMedCrossRefGoogle Scholar
  161. 161.
    Spell DW, Jones DV Jr, Harper WF, David Bessman J (2004) The value of a complete blood count in predicting cancer of the colon. Cancer Detect Prev 28(1):37–42PubMedCrossRefGoogle Scholar
  162. 162.
    Pierce CN, Larson DF (2005) Inflammatory cytokine inhibition of erythropoiesis in patients implanted with a mechanical circulatory assist device. Perfusion 20(2):83–90PubMedCrossRefGoogle Scholar
  163. 163.
    Hamilton CA, Miller WH, Al Benna S, Brosnan MJ, Drummond RD, McBride MW, Dominiczak AF (2004) Strategies to reduce oxidative stress in cardiovascular disease. Clin Sci (Lond) 106(3):219–234CrossRefGoogle Scholar
  164. 164.
    Berry C, Hamilton CA, Brosnan MJ, Magill FG, Berg GA, McMurray JJ, Dominiczak AF (2000) Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries. Circulation 101(18):2206–2212PubMedGoogle Scholar
  165. 165.
    Hokamaki J, Kawano H, Yoshimura M, Soejima H, Miyamoto S, Kajiwara I, Kojima S, Sakamoto T, Sugiyama S, Hirai N, Shimomura H, Nagayoshi Y, Tsujita K, Shioji I, Sasaki S, Ogawa H (2004) Urinary biopyrrins levels are elevated in relation to severity of heart failure. J Am Coll Cardiol 43(10):1880–1885PubMedCrossRefGoogle Scholar
  166. 166.
    McMurray J, Chopra M, Abdullah I, Smith WE, Dargie HJ (1993) Evidence of oxidative stress in chronic heart failure in humans. Eur Heart J 14(11):1493–1498PubMedGoogle Scholar
  167. 167.
    Keith M, Geranmayegan A, Sole MJ, Kurian R, Robinson A, Omran AS, Jeejeebhoy KN (1998) Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol 31(6):1352–1356PubMedCrossRefGoogle Scholar
  168. 168.
    Nonaka-Sarukawa M, Yamamoto K, Aoki H, Takano H, Katsuki T, Ikeda U, Shimada K (2003) Increased urinary 15-F2t-isoprostane concentrations in patients with non-ischaemic congestive heart failure: a marker of oxidative stress. Heart 89(8):871–874PubMedCrossRefGoogle Scholar
  169. 169.
    Wykretowicz A, Furmaniuk J, Smielecki J, Deskur-Smielecka E, Szczepanik A, Banaszak A, Wysocki H (2004) The oxygen stress index and levels of circulating interleukin-10 and interleukin-6 in patients with chronic heart failure. Int J Cardiol 94(2–3):283–287PubMedCrossRefGoogle Scholar
  170. 170.
    White M, Ducharme A, Ibrahim R, Whittom L, Lavoie J, Guertin MC, Racine N, He Y, Yao G, Rouleau JL, Schiffrin EL, Touyz RM (2006) Increased systemic inflammation and oxidative stress in patients with worsening congestive heart failure: improvement after short-term inotropic support. Clin Sci (Lond) 110(4):483–489CrossRefGoogle Scholar
  171. 171.
    White M, Lepage S, Lavoie J, De Denus S, Leblanc MH, Gossard D, Whittom L, Racine N, Ducharme A, Dabouz F, Rouleau JL, Touyz R (2007) Effects of combined candesartan and ACE inhibitors on BNP, markers of inflammation and oxidative stress, and glucose regulation in patients with symptomatic heart failure. J Card Fail 13(2):86–94PubMedCrossRefGoogle Scholar
  172. 172.
    Doehner W, Anker SD (2005) Uric acid in chronic heart failure. Semin Nephrol 25(1):61–66PubMedCrossRefGoogle Scholar
  173. 173.
    Anker SD, Doehner W, Rauchhaus M, Sharma R, Francis D, Knosalla C, Davos CH, Cicoira M, Shamim W, Kemp M, Segal R, Osterziel KJ, Leyva F, Hetzer R, Ponikowski P, Coats AJ (2003) Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging. Circulation 107(15):1991–1997PubMedCrossRefGoogle Scholar
  174. 174.
    Batin P, Wickens M, McEntegart D, Fullwood L, Cowley AJ (1995) The importance of abnormalities of liver function tests in predicting mortality in chronic heart failure. Eur Heart J 16(11):1613–1618PubMedGoogle Scholar
  175. 175.
    Cicoira M, Zanolla L, Rossi A, Golia G, Franceschini L, Brighetti G, Zeni P, Zardini P (2002) Elevated serum uric acid levels are associated with diastolic dysfunction in patients with dilated cardiomyopathy. Am Heart J 143(6):1107–1111PubMedCrossRefGoogle Scholar
  176. 176.
    Pascual-Figal DA, Hurtado-Martinez JA, Redondo B, Antolinos MJ, Ruiperez JA, Valdes M (2007) Hyperuricaemia and long-term outcome after hospital discharge in acute heart failure patients. Eur J Heart Fail 9(5):518–524PubMedCrossRefGoogle Scholar
  177. 177.
    Jortani SA, Valdes R Jr (2001) Mammalian cardenolides as biomarkers in congestive heart failure. Cardiovasc Toxicol 1(2):165–170PubMedCrossRefGoogle Scholar
  178. 178.
    Balzan S, Neglia D, Ghione S, D’Urso G, Baldacchino MC, Montali U, L’Abbate A (2001) Increased circulating levels of ouabain-like factor in patients with asymptomatic left ventricular dysfunction. Eur J Heart Fail 3(2):165–171PubMedCrossRefGoogle Scholar
  179. 179.
    Sjovall K, Nilsson B, Einhorn N (2002) The significance of serum CA 125 elevation in malignant and nonmalignant diseases. Gynecol Oncol 85(1):175–178PubMedCrossRefGoogle Scholar
  180. 180.
    Kouris NT, Zacharos ID, Kontogianni DD, Goranitou GS, Sifaki MD, Grassos HE, Kalkandi EM, Babalis DK (2005) The significance of CA125 levels in patients with chronic congestive heart failure. Correlation with clinical and echocardiographic parameters. Eur J Heart Fail 7(2):199–203PubMedCrossRefGoogle Scholar
  181. 181.
    D’Aloia A, Faggiano P, Aurigemma G, Bontempi L, Ruggeri G, Metra M, Nodari S, Dei Cas L (2003) Serum levels of carbohydrate antigen 125 in patients with chronic heart failure: relation to clinical severity, hemodynamic and Doppler echocardiographic abnormalities, and short-term prognosis. J Am Coll Cardiol 41(10):1805–1811PubMedCrossRefGoogle Scholar
  182. 182.
    Kosar F, Aksoy Y, Ozguntekin G, Ozerol I, Varol E (2006) Relationship between cytokines and tumour markers in patients with chronic heart failure. Eur J Heart Fail 8(3):270–274PubMedCrossRefGoogle Scholar
  183. 183.
    Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, Andre S, Crijns HJ, Gabius HJ, Maessen J, Pinto YM (2004) Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation 110(19):3121–3128PubMedCrossRefGoogle Scholar
  184. 184.
    van Kimmenade RR, Januzzi JL Jr, Ellinor PT, Sharma UC, Bakker JA, Low AF, Martinez A, Crijns HJ, MacRae CA, Menheere PP, Pinto YM (2006) 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 48(6):1217–1224PubMedCrossRefGoogle Scholar
  185. 185.
    Granger CB, McMurray JJ (2006) Using measures of disease progression to determine therapeutic effect: a sirens’ song. J Am Coll Cardiol 48(3):434–437PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • J. Paul Rocchiccioli
    • 1
  • John J. V. McMurray
    • 1
  • Anna F. Dominiczak
    • 1
  1. 1.BHF Glasgow Cardiovascular Research CentreUniversity of GlasgowGlasgowScotland, UK

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