Neurohormonal activation and inflammation in chronic cardiopulmonary disease: a brief systematic review

  • Wolfram Doehner
  • Stephan von Haehling
  • Stefan D. Anker
  • Mitja Lainscak
Review article


Chronic cardiopulmonary disease typically induces and maintains (over)activation of several phylogenetically old adaptational and defensive mechanisms. Activation was usually needed for a limited period during acute danger or injury. In chronic disease conditions, however, those mechanisms are kept activated for longer periods. Eventually, irreversible damage is done and this contributes to impaired function and worse prognosis in a variety of chronic disease. Landmark trials in chronic heart failure have provided robust evidence for prognostic benefit for neurohormonal antagonists. Retrospective and epidemiological data for their beneficial effect in chronic obstructive pulmonary disease begin to accumulate and new fields (e.g. cancer and stroke) could be pending in the future.


Cachexia Cancer Chronic heart failure Chronic obstructive pulmonary disease Inflammation Neurohormones Renin-angiotensin-aldosterone Stroke Sympatethic system 


  1. von Haehling S, Lainscak M, Springer J, Anker SD (2009) Cardiac Cachexia: a systematic overview. Pharmacol Ther 121: 227–252PubMedCrossRefGoogle Scholar
  2. Andreas S, Anker SD, Scanlon PD, Somers VK (2005) Neurohumoral activation as a link to systemic manifestations of chronic lung disease. Chest 128: 3618–3624PubMedCrossRefGoogle Scholar
  3. Swedberg K, Eneroth P, Kjekshus J, Snapinn S (1990) Effects of enalapril and neuroendokrine activation on prognosis in severe congestive heart failure (follow-up of the CONSENSUS trial). CONSENSUS Trial Study Group. Am J Cardiol 66: 40D–44DPubMedCrossRefGoogle Scholar
  4. Strassburg S, Anker SD (2006) Metabolic and immunologic derangements in cardiac cachexia: where to from here? Heart Fail Rev 11: 57–64PubMedCrossRefGoogle Scholar
  5. Filippatos GS, Anker SD, Kremastinos DT (2005) Pathophysiology of peripheral muscle wasting in cardiac cachexia. Curr Opin Clin Nutr Metab Care 8: 249–254PubMedCrossRefGoogle Scholar
  6. Hawkins NM, Petrie MC, Jhund PS, Chalmers GW, Dunn FG, McMurray JJV (2009) Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology. Eur J Heart Fail 11: 130–139PubMedCrossRefGoogle Scholar
  7. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ (2006) Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367: 1747–1757PubMedCrossRefGoogle Scholar
  8. Firlei N, Lamprecht B, Schirnhofer L, Kaiser B, Studnicka M (2007) The prevalence of COPD in Austria – the expected change over the next decade. Wien Klin Wochenschr 119: 513–518PubMedCrossRefGoogle Scholar
  9. Lainscak M, Majc Hodoscek L, Düngen HD, Rauchhaus M, Doehner W, Anker SD, et al (2009) The burden of chronic obstructive pulmonary disease in patients hospitalized for heart failure. Wien Klin Wochenschrift 121: 309–313Google Scholar
  10. Staszewsky L, Wong M, Masson S, Barlera S, Carretta E, Maggioni AP, et al (2007) Clinical, neurohormonal, and inflammatory markers and overall prognostic role of chronic obstructive pulmonary disease in patients with heart failure: data from the Val-HeFT heart failure trial. J Card Fail 13: 797–804PubMedCrossRefGoogle Scholar
  11. Narins RG, Jones ER, Stom MC, Rudnick MR, Bastl CP (1982) Diagnostic strategies in disorders of fluid, electrolyte and acid-base homeostasis. Am J Med 72: 496–520PubMedCrossRefGoogle Scholar
  12. Anand IS, Fisher LD, Chiang YT, Latini R, Masson S, Maggioni AP, et al (2003) Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation 107: 1278–1283PubMedCrossRefGoogle Scholar
  13. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, et al (2008) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur J Heart Fail 10: 933–989PubMedCrossRefGoogle Scholar
  14. Grassi G, Seravalle G, Calhoun DA, Matturri M, Mancia G, Zanchetti A (1992) Monitoring of sympathetic activity in man: physiology and pharmacology. Eur Heart J 13 [Suppl A]: 22–25PubMedGoogle Scholar
  15. Watson AM, Hood SG, May CN (2006) Mechanisms of sympathetic activation in heart failure. Clin Exp Pharmacol Physiol 33: 1269–1274PubMedCrossRefGoogle Scholar
  16. Waagstein F, Hjalmarson A, Varnauskas E, Wallentin I (1975) Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J 37: 1022–1036PubMedCrossRefGoogle Scholar
  17. Straub RH, Besedovsky HO, Del Rey A (2007) Why are there analogous disease mechanisms in chronic inflammatory diseases? Wien Klin Wochenschr 119: 444–454PubMedCrossRefGoogle Scholar
  18. Lainscak M, von Haehling S, Anker SD (2009) Natriuretic peptides and other biomarkers in chronic heart failure: from BNP, NT-proBNP, and MR-proANP to routine biochemical markers. Int J Cardiol 132: 303–311PubMedCrossRefGoogle Scholar
  19. Tang YD, Katz SD (2006) Anemia in chronic heart failure: prevalence, etiology, clinical correlates, and treatment options. Circulation 113: 2454–2461PubMedCrossRefGoogle Scholar
  20. Lainscak M, von Haehling S, Sarc I, Ziherl K, Doehner W, Suskovic S, et al (2008) Anemia predicts survival in patients with chronic obstructive pulmonary disease. Eur Respir J 32 [Suppl]: 43sGoogle Scholar
  21. Rauchhaus M, Doehner W, Francis DP, Davos C, Kemp M, Liebenthal C, et al (2000) Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation 102: 3060–3070PubMedGoogle Scholar
  22. Fabbri LM, Luppi F, Beghe B, Rabe KF (2008) Complex chronic comorbidities of COPD. Eur Respir J 31: 204–212PubMedCrossRefGoogle Scholar
  23. Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al for the Global Initiative for Chronic Obstructive Lung Disease (2007) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 176: 532–555PubMedCrossRefGoogle Scholar
  24. Sin DD, Man SFP (2006) Pharmacotherapy for mortality reduction in chronic obstructive pulmonary disease. Proc Am Thorac Soc 3: 624–629PubMedCrossRefGoogle Scholar
  25. Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB (2008) Risk for death associated with medicatins for recently diagnosed chronic obstructive pulmonary disease. Ann Intern Med 149: 380–390PubMedGoogle Scholar
  26. Calverly PMA, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al (2007) Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 356: 775–789CrossRefGoogle Scholar
  27. Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ (2008) Comorbidities in chronic obstructive pulmonary disease. Proc AM Thorac Soc 5: 549–555PubMedCrossRefGoogle Scholar
  28. Sin DD, Anthonisen NR, Soriano JB, Agusti AG (2006) Mortality in COPD: role of comorbidities. Eur Respir J 28: 1245–1257PubMedCrossRefGoogle Scholar
  29. Mancini GBJ, Etminan M, Zhang B, Levesque LE, FitzGerald JM, Brophy JM (2006) Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol 47: 2554–2560PubMedCrossRefGoogle Scholar
  30. Lainscak M, Cleland JG, Lenzen MJ, Follath F, Komajda M, Swedberg K (2007) International variations in the treatment and co-morbidity of left ventricular systolic dysfunction: data from the EuroHeart Failure Survey. Eur J Heart Fail 9: 292–299PubMedCrossRefGoogle Scholar
  31. Lainscak M, Moullet C, Schön N, Tendera M (2007) Treatment of chronic heart failure with carvedilol in daily practice: the SATELLITE survey experience. Int J Cardiol 122: 149–155PubMedCrossRefGoogle Scholar
  32. Gottlieb SS, McCarter RJ, Vogel RA (1998) Effects of beta-blockade on mortality among high-risk and low-risk patietns after myocardial infarction. N Engl J Med 339: 489–497PubMedCrossRefGoogle Scholar
  33. Van Gestel YRBM, Hoeks SE, Sin DD, Welten GMJM, Schouten O, Witteveen HJ, et al (2008) Impact of cardioselective β-blockers on mortality in patients with chronic obstructive pulmonary disease and atherosclerosis. Am J Respir Crit Care Med 178: 695–700PubMedCrossRefGoogle Scholar
  34. Dransfield MT, Rowe SM, Johnson JE, Bailey WC, Gerald LB (2008) Use of β blockers and the risk of death in hospitalized patients with acute exacerbations of COPD. Thorax 63: 301–305PubMedCrossRefGoogle Scholar
  35. von Haehling S, Anker SD (2005) Statins for heart failure: at the crossroads between cholesterol reduction and pleiotropism? Heart 91: 1–2PubMedCrossRefGoogle Scholar
  36. Keddissi JI, Younis WG, Chbeir EA, Daher NN, Dernaika TA, Kinasewitz GT (2007) The use of statins and lung function in current and former smokers. Chest 132: 1764–1771PubMedCrossRefGoogle Scholar
  37. Rauchhaus M, Coats AJS, Anker SD (2000) The endotoxin-lipoprotein hypothesis. Lancet 356: 930–933PubMedCrossRefGoogle Scholar
  38. Andreas S, Herrmann-Lingen C, Raupach T, Lüthje L, Fabricius JA, Hruska N, et al (2006) Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled trial. Eur Respir J 27: 972–979PubMedGoogle Scholar
  39. Lainscak M, Andreas S, Scanlon PD, Somers VK, Anker SD (2006) Ghrelin and neurohormonal antagonists in the treatment of cachexia associated with cardiopulmonary disease. Int Med 45: 837CrossRefGoogle Scholar
  40. Düngen HD, Apostolović S, Inkrot S, Tahirovic E, Krackhardt F, Pavlovic M, et al; CIBIS-ELD Investigators, Subproject Multicenter Trials in the Competence Network Heart Failure (2008) Bisoprolol vs. carvedilol in elderly patients with heart failure: rationale and design of the CIBIS-ELD trial. Clin Res Cardiol 97: 578–586PubMedCrossRefGoogle Scholar
  41. Schuler J, Dückelmann C, Beindl W, Prinz E, Michalski T, Pichler M (2008) Polypharmacy and inappropriate prescribing in elderly internal-medicine patients in Austria. Wien Klin Wochenschr 120: 733–741PubMedCrossRefGoogle Scholar
  42. Schünemann M, Anker SD, Rauchhaus M (2008) Cancer fatigue syndrome reflects clinically non-overt heart failure: an approach towards onco-cardiology. Nat Clin Pract Oncol 5: 632–633PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Wolfram Doehner
    • 1
    • 2
  • Stephan von Haehling
    • 2
  • Stefan D. Anker
    • 2
    • 3
  • Mitja Lainscak
    • 2
    • 4
  1. 1.Center for Stroke Research BerlinCharitéBerlinGermany
  2. 2.Applied Cachexia ResearchCharité UniversitätsmedizinBerlinGermany
  3. 3.Center for Clinical and Basic ResearchIRCCS San RaffaeleRomeItaly
  4. 4.Division of CardiologyUniversity Clinic of Respiratory and Allergic Diseases GolnikGolnikSlovenia

Personalised recommendations