Aktuelle Ernährungsmedizin 2009; 34(4): e1-e10
DOI: 10.1055/s-0028-1090235
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Von der Herzinsuffizienz zur kardialen Kachexie: Klinik und pathophysiologische Mechanismen

From Heart Failure to Cardiac Cachexia: Clinical Aspects and PathophysiologyT.  Kung1 , S. von  Haehling1
  • 1Medizinische Klinik mit Schwerpunkt Kardiologie, Angewandte Kachexieforschung, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
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Publikationsverlauf

Publikationsdatum:
03. Juli 2009 (online)

Zusammenfassung

Eine Kachexie entwickelt sich im Verlauf vieler chronischer Krankheiten wie maligner Tumoren, Sepsis, chronischer Herz- oder Niereninsuffizienz, rheumatoider Arthritis oder AIDS. Bei oftmals bereits schlechter Prognose der Grunderkrankung ist das Auftreten einer Kachexie meist nochmals mit einer Erhöhung der Morbidität und Mortalität assoziert. Leider ist die Kachexie noch nicht Bestandteil des alltäglichen Sprachgebrauchs des Klinikers geworden, obwohl ihre klinische Bedeutung kaum zu überschätzen ist. Die Ursachen sind sicherlich in der schwierigen Frage der eindeutigen Definition der Kachexie, aber auch im Fehlen einer spezifischen Therapie zu suchen. Das Ziel dieses Artikels ist es, die klinische Relevanz des Problems Kachexie bei chronischer Herzinsuffizienz aufzuzeigen. Darüber hinaus diskutieren wir pathophysiologische Mechanismen der Kachexie unter besonderer Beachtung der inflammatorischen Stimuli und der Regulation des Appetits. Einige mögliche Therapieansätze werden diskutiert.

Abstract

Cachexia develops in the course of many chronic diseases such as malign tumours, chronic heart failure, chronic kidney failure, rheumatoid arthritis, or AIDS. In most cases, the development of cachexia worsens morbidity and mortality of the underlying disease. Unfortunately, the term „cachexia” is still not routinely used by clinicians, although the clinical impact of cachexia is difficult to overestimate. The reasons include the difficult question of a uniform definition of cachexia, but also the absence of specific therapies. The aim of this article is to provide an overview of the pathophysiology and potential therapeutic approaches to cachexia in chronic heart failure. We particularly discuss the role of inflammation and the regulation of appetite.

Literatur

  • 1 Haehling S von, Lainscak M, Springer J. et al . Cardiac cachexia: A systematic overview.  Pharmacol Ther. 2009;  121 227-252
  • 2 Springer J, Haehling S von, Anker S D. The need for a standartized definition for cachexia in chronic illness.  Nat Clin Pract Endocrinol Metab. 2006;  2 416-417
  • 3 Evans W J, Morley J E, Argilés J. et al . Cachexia: A new definition.  Clin Nutr. 2008;  27 793-799
  • 4 Mann J, Hilgers K F, Veelken R. et al . The kidneys and the heart.  Dtsch Med Wochenschr. 2008;  133 1839-1843
  • 5 Dalla Libera L, Vescovo G, Volterrani M. Physiological basis for contractile dysfunction in heart failure.  Curr Pharm Des. 2008;  14 2572-2581
  • 6 Ventura-Clapier R, Garnier A, Veksler V. Energy metabolism in heart failure.  J Physiol. 2004;  555 1-13
  • 7 Kjaer A, Hesse B. Heart failure and neuroendocrine activation: diagnostic, prognostic and therapeutic perspectives.  Clin Physiol. 2001;  21 661-672
  • 8 Haehling S von, Jankowska E A, Anker S D. Tumour necrosis factor-α and the failing heart – pathophysiology and therapeutic implications.  Basic Res Cardiol. 2004;  99 18-28
  • 9 Wolfe R R. Control of muscle protein breakdown: effects of activity and nutritional states.  Int J Sport Nutr Exerc Metab. 2001;  11 164-169
  • 10 Fearon K C, Voss A C, Hustead D S. Cancer Cachexia Study Group . Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis.  Am J Clin Nutr. 2006;  83 1345-1350
  • 11 Anker S D, Coats A J. Cachexia in heart failure is bad for you.  Eur Heart J. 1998;  19 191-193
  • 12 Mulligan K, Tai V W, Schambelan M. Cross-sectional and longitudinal evaluation of body composition in men with HIV infection.  J Acquir Immune Defic Syndr Hum Retrovirol. 1997;  15 43-48
  • 13 Kalantar-Zadeh K, Kopple J D. Obesity paradox in patients on maintenance dialysis.  Contrib Nephrol. 2006;  151 57-69
  • 14 Cowie M R, Mosterd A, Wood D A. et al . The epidemiology of heart failure.  Eur Heart J. 1997;  18 208-225
  • 15 Davies M, Hobbs F, Davis R. et al . Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study.  Lancet. 2001;  358 439-444
  • 16 Ho K K, Pinsky J L, Kannel W B, Levy D. The epidemiology of heart failure: the Framingham Study.  J Am Coll Cardiol. 1993;  22 6A-13A
  • 17 Anker S D, Ponikowski P, Varney S. et al . Wasting as independent risk factor for mortality in chronic heart failure.  Lancet. 1997;  349 1050-1053
  • 18 Cowie M R, Wood D A, Coats A J. et al . Incidence and aetiology of heart failure; a population-based study.  Eur Heart J. 1999;  20 421-428
  • 19 Kannel W B. Vital epidemiologic clues in heart failure.  J Clin Epidemiol. 2000;  53 229-235
  • 20 Giles T. The cost-effective way forward for the management of the patient with heart failure.  Cardiology. 1996;  67 33-39
  • 21 Stewart S, MacIntyre K, Hole D J. et al . More „malignant” than cancer? Five-year survival following a first admission for heart failure.  Eur J Heart Fail. 2001;  3 315-322
  • 22 Owan T E, Hodge D O, Herges R M. et al . Trends in prevalence and outcome of heart failure with preserved ejection fraction.  N Engl J Med. 2006;  355 251-259
  • 23 Haehling S von, Doehner W, Anker S D. Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure.  Cardiovasc Res. 2007;  73 298-309
  • 24 Toth M J, Matthews D E. Whole-body protein metabolism in chronic heart failure: relationship to anabolic and catabolic hormones.  J Parenter Enteral Nutr. 2006;  30 194-201
  • 25 Strassburg S, Springer J, Anker S D. Muscle wasting in cardiac cachexia.  Int J Biochem Cell Biol. 2005;  37 1938-1947
  • 26 Meltzer J S, Moitra V K. The nutritional and metabolic support of heart failure in the intensive care unit.  Curr Opin Clin Nutr Metab Care. 2008;  11 140-146
  • 27 Anker S D, Clark A L, Teixeira M M. et al . Loss of bone mineral in patients with cachexia due to chronic heart failure.  Am J Cardiol. 1999;  83 612-615
  • 28 Doehner W, Anker S D. Cardiac cachexia in early literature: a review of research prior to Medline.  Int J Cardiol. 2002;  85 7-14
  • 29 Lainscak M, Keber I, Anker S D. Body composition changes in patients with systolic heart failure treated with beta blockers: a pilot study.  Int J Cardiol. 2006;  112 234-242
  • 30 Anker S D, Clark A L, Winkler R. et al . Statin use and survival in patients with chronic heart failure – results from two observational studies with 5200 patients.  Int J Cardiol. 2006;  112 234-242
  • 31 Yusuf S. The global problem of cardiovascular disease.  Int J Clin Pract Suppl. 1998;  94 3-6
  • 32 Pardo Silva M C, De Laet C, Nusselder W J. et al . Adult obesity and number of years lived with and without cardiovascular disease.  Obesity (Silver Spring). 2006;  14 1264-1273
  • 33 Darnton-Hill I, Coyne E T. Feast and famine: socioeconomic disparities in global nutrition and health.  Public Health Nutr. 1998;  1 23-31
  • 34 Menotti A, Blackburn H, Kromhout D. et al . Cardiovascular risk factors as determinants of 25-year all-cause mortality in the seven countries study.  Eur J Epidemiol. 2001;  17 337-346
  • 35 Horwich T B, Fonarow G C. Reverse epidemiology beyond dialysis patients: chronic heart failure, geriatrics, rheumatoid arthritis, COPD, and AIDS.  Semin Dial. 2007;  20 549-553
  • 36 Kalantar-Zadeh K, Anker S D, Coats A J. et al . Obesity paradox as a component of reverse epidemiology in heart failure.  Arch Intern Med. 2005;  165 1797
  • 37 Kalantar-Zadeh K, Kilpatrick R D, Kuwae N. et al . Reverse epidemiology: a spurious hypothesis or a hardcore reality?.  Blood Purif. 2005;  23 57-63
  • 38 Davos C H, Doehner W, Rauchhaus M. et al . Body mass and survival in patients with chronic heart failure without cachexia: the importance of obesity.  J Card Fail. 2003;  9 29-35
  • 39 Horwich T B, Fonarow G C, Hamilton M A. et al . The relationship between obesity and mortality in patients with heart failure.  J Am Coll Cardiol. 2001;  38 789-795
  • 40 Rauchhaus M, Clark A L, Doehner W. et al . The relationship between cholesterol and survival in patients with chronic heart failure.  J Am Coll Cardiol. 2003;  42 1933-1940
  • 41 Horwich T B, Hamilton M A, Maclellan W R. et al . Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure.  J Card Fail. 2002;  8 216-224
  • 42 Stanley W C, Sabbah H N. Metabolic therapy for ischemic heart disease: the rationale for inhibition of fatty acid oxidation.  Heart Fail Rev. 2005;  10 275-279
  • 43 Osorio J C, Stanley W C, Linke A. et al . Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid X receptor-α in pacing-induced heart failure.  Circulation. 2002;  106 606-612
  • 44 Remondino A, Rosenblatt-Velin N, Montessuit C. et al . Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction.  J Mol Cell Cardiol. 2000;  32 2025-2034
  • 45 Nascimben L, Ingwall J S, Lorell B H. et al . Mechanisms for increased glycolysis in the hypertrophied rat heart.  Hypertension. 2004;  44 662-667
  • 46 Kalsi K K, Smolenski R T, Pritchard R D. et al . Energetics and function of the failing human heart with dilated or hypertrophic cardiomyopathy.  Eur J Clin Invest. 1999;  29 469-477
  • 47 Razeghi P, Young M E, Alcorn J L. et al . Metabolic gene expression in fetal and failing human heart.  Circulation. 2001;  104 2923-2931
  • 48 Taylor M, Wallhaus T R, Degrado T R. et al . An evaluation of myocardial fatty acid and glucose uptake using PET with [18F]fluoro-6-thia-heptadecanoic acid and [18F]FDG in Patients with Congestive Heart Failure.  J Nucl Med. 2001;  42 55-62
  • 49 Stanley W C, Recchia F A, Lopaschuk G D. Myocardial substrate metabolism in the normal and failing heart.  Physiol Rev. 2005;  85 1093-1129
  • 50 Levine B, Kalman J, Mayer L. et al . Elevated circulating levels of tumor necrosis factor in severe chronic heart failure.  N Engl J Med. 1990;  323 236-241
  • 51 Rauchhaus M, Doehner W, Francis D P. et al . Plasma cytokine parameters and mortality in patients with chronic heart failure.  Circulation. 2000;  102 3060-3067
  • 52 Chen D, Assad-Kottner C, Orrego C. et al . Cytokines and acute heart failure.  Crit Care Med. 2008;  36 9-16
  • 53 Celis R, Torre-Martinez G, Torre-Amione G. Evidence for activation of immune system in heart failure: is there a role for anti-inflammatory therapy?.  Curr Opin Cardiol. 2008;  23 254-260
  • 54 Anker S D, Haehling S von. Inflammatory mediators in chronic heart failure: an overview.  Heart. 2004;  90 464-470
  • 55 Deswal A, Petersen N J, Feldman A M. et al . Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST).  Circulation. 2001;  103 2055-2059
  • 56 Ferrari R, Bachetti T, Confortini R. et al . Tumor necrosis factor soluble receptors in patients with various degrees of congestive heart failure.  Circulation. 1995;  92 1479-1486
  • 57 Sharma R, Coats A J, Anker S D. The role of inflammatory mediators in chronic heart failure: cytokines, nitric oxide, and endothelin-1.  Int J Cardiol. 2000;  72 175-186
  • 58 Giroir B P, Johnson J H, Brown T. et al . The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia.  J Clin Invest. 1992;  90 693-698
  • 59 Kapadia S, Lee J, Torre-Amione G. et al . Tumor necrosis factor-α gene and protein expression in adult feline myocardium after endotoxin administration.  J Clin Invest. 1995;  96 1042-1052
  • 60 Meldrum D R. Tumor necrosis factor in the heart.  Am J Physiol. 1998;  274 577-595
  • 61 Jankowska E A, Haehling S von, Czarny A. et al . Activation of the NF-κB system in peripheral blood leukocytes from patients with chronic heart failure.  Eur J Heart Fail. 2005;  7 984-990
  • 62 Niebauer J, Volk H D, Kemp M. et al . Endotoxin and immune activation in chronic heart failure: a prospective cohort study.  Lancet. 1999;  353 1838-1842
  • 63 Baumann H, Gauldie J. The acute phase response.  Immunol Today. 1994;  15 74-80
  • 64 Kotler D P. Cachexia.  Ann Intern Med. 2000;  133 622-634
  • 65 Adams J. The proteasome: structure, function, and role in the cell.  Cancer Treat Rev. 2003;  29 3-9
  • 66 Lecker S H, Goldberg A L, Mitch W E. Protein degradation by the ubiquitin-proteasome pathway in normal and disease states.  J Am Soc Nephrol. 2006;  17 1807-1819
  • 67 Llovera M, Garcia-Martinez C, Agell N. et al . Ubiquitin and proteasome gene expression is increased in skeletal muscle of slim AIDS patients.  Int J Mol Med. 1998;  2 69-73
  • 68 Klaude M, Fredriksson K, Tjäder I. et al . Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis.  Clin Sci (Lond). 2007;  112 499-506
  • 69 Wang W J, Li Q Q, Xu J D. et al . Over-expression of ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells.  Int J Oncol. 2008;  33 1037-1045
  • 70 Rajan V R, Mitch W E. Muscle wasting in chronic kidney disease: the role of the ubiquitin proteasome system and its clinical impact.  Pediatr Nephrol. 2008;  23 527-535
  • 71 Zamir O, Hasselgren P O, Kunkel S L. et al . Evidence that tumor necrosis factor participates in the regulation of muscle proteolysis during sepsis.  Arch Surg. 1992;  127 170-174
  • 72 Goodman M N. Tumor necrosis factor induces skeletal muscle protein breakdown in rats.  Am J Physiol. 1991;  260 727-730
  • 73 Zamir O, Hasselgren P O, Allmen D von. et al . In vivo administration of interleukin-1α induces muscle proteolysis in normal and adrenalectomized rats.  Metabolism. 1993;  42 204-208
  • 74 Goodman M N. Interleukin-6 induces skeletal muscle protein breakdown in rats.  Proc Soc Exp Biol Med. 1994;  205 182-185
  • 75 Hall-Angerås M, Angerås U, Zamir O. et al . Interaction between corticosterone and tumor necrosis factor stimulated protein breakdown in rats skeletal muscle, similar to sepsis.  Surgery. 1990;  108 460-466
  • 76 Richardson P G, Mitsiades C, Schlossman R. et al . Bortezomib in the front-line treatment of multiple myeloma.  Expert Rev Anticancer Ther. 2008;  8 1053-1072
  • 77 San Miguel J F, Schlag R, Khuageva N K. et al, VISTA Trial Investigators . Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.  N Engl J Med. 2008;  359 906-917
  • 78 Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences.  Cell. 1986;  46 705-716
  • 79 Baeuerle P A, Baltimore D. IκB: a specific inhibitor of the NF-κ B transcription factor.  Science. 1988;  242 540-546
  • 80 Ghosh S, May M J, Kopp E B. NF-κ B and Rel proteins: evolutionarily conserved mediators of immune responses.  Annu Rev Immunol. 1998;  16 225-260
  • 81 Langen R C, Schols A M, Kelders M C. et al . Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-κB.  FASEB J. 2001;  15 1169-1180
  • 82 Wisdom R. AP-1: one switch for many signals.  Exp Cell Res. 1999;  253 180-185
  • 83 Kaminska B, Pyrzynska B, Ciechomska I. et al . Modulation of the composition of AP-1 complex and its impact on transcriptional activity.  Acta Neurobiol Exp (Wars). 2000;  60 395-402
  • 84 Moore K W, Waal Malefyt R de, Coffman R L. et al . Interleukin-10 and the interleukin-10 receptor.  Annu Rev Immunol. 2001;  19 683-765
  • 85 Cassatella M A, Meda L, Gasperini S. et al . Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation.  J Exp Med. 1994;  179 1695-1699
  • 86 Hart P H, Hunt E K, Bonder C S. et al . Regulation of surface and soluble TNF receptor expression on human monocytes and synovial fluid macrophages by IL-4 and IL-10.  J Immunol. 1996;  157 3672-3680
  • 87 Bogdan C, Vodovotz Y, Nathan C. Macrophage deactivation by interleukin 10.  J Exp Med. 1991;  174 1549-1555
  • 88 Opal S M, Huber C E. The role of interleukin-10 in critical illness.  Curr Opin Infect Dis. 2000;  13 221-226
  • 89 Bolger A P, Sharma R, Haehling S von. et al . Effect of interleukin-10 on the production of tumor necrosis factor-α by peripheral blood mononuclear cells from patients with chronic heart failure.  Am J Cardiol. 2002;  90 384-389
  • 90 Gullestad L, Aass H, Fjeld J G. et al . Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure.  Circulation. 2001;  103 220-225
  • 91 Guirao X, Kumar A, Katz J. et al . Catecholamines increase monocyte TNF receptors and inhibit TNF through beta 2-adrenoreceptor activation.  Am J Physiol. 1997;  273 1203-1208
  • 92 van der Poll T, Lowry S F. Epinephrine inhibits endotoxin-induced IL-1 beta production: roles of tumor necrosis factor-α and IL-10.  Am J Physiol. 1997;  273 R1885-R1890
  • 93 Haehling S von, Genth-Zotz S, Bolger A P. et al . Effect of noradrenaline and isoproterenol on lipopolysaccharide-induced tumor necrosis factor-α production in whole blood from patients with chronic heart failure and the role of beta-adrenergic receptors.  Am J Cardiol. 2005;  95 885-889
  • 94 Van der Poll T, Coyle S M, Barbosa K. et al . Epinephrine inhibits tumor necrosis factor-α and potentiates interleukin 10 production during human endotoxemia.  J Clin Invest. 1996;  97 713-719
  • 95 Beck I M, Vanden Berghe W, Vermeulen L. et al . Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-κB inhibition.  EMBO J. 2008;  27 1682-1693
  • 96 Auphan N, Donato J A Di, Rosette C. et al . Immunosuppression by glucocorticoids: inhibition of NF-κ B activity through induction of I κ B synthesis.  Science. 1995;  270 286-290
  • 97 Scheinman R I, Cogswell P C, Lofquist A K. et al . Role of transcriptional activation of I κ B α in mediation of immunosuppression by glucocorticoids.  Science. 1995;  270 283-286
  • 98 Pekkarinen A, Ilsalo E, Kasanen A. et al . The adrenosympathetic and adrenocortical function in cardiac insufficiency.  Am J Cardiol. 1960;  5 604-612
  • 99 Anker S D, Clark A L, Kemp M. et al . Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting.  J Am Coll Cardiol. 1997;  30 997-1001
  • 100 Schulze P C, Gielen S, Adams V. et al . Muscular levels of proinflammatory cytokines correlate with a reduced expression of insulinlike growth factor-I in chronic heart failure.  Basic Res Cardiol. 2003;  98 267-274
  • 101 Rauchhaus M, Coats A J, Anker S D. The endotoxin-lipoprotein hypothesis.  Lancet. 2000;  356 930-933
  • 102 Flegel W A, Baumstark M W, Weinstock C. et al . Prevention of endotoxin-induced monokine release by human low- and high-density lipoproteins and by apolipoprotein A-I.  Infect Immun. 1993;  61 5140-5146
  • 103 Wurfel M M, Kunitake S T, Lichenstein H. et al . Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS.  J Exp Med. 1994;  180 1025-1035
  • 104 Genth-Zotz S, Haehling S von, Bolger A P. et al . Pathophysiologic quantities of endotoxin-induced tumor necrosis factor-α release in whole blood from patients with chronic heart failure.  Am J Cardiol. 2002;  90 1226-1230
  • 105 Marín Caro M M, Laviano A, Pichard C. Impact of nutrition on quality of life during cancer.  Curr Opin Clin Nutr Metab Care. 2007;  10 480-487
  • 106 Tatemoto K, Carlquist M, Mutt V. Neuropeptide Y – a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide.  Nature. 1982;  296 659-660
  • 107 Vardatsikos G, Sahu A, Srivastava A. The insulin-like growth factor family: Molecular mechanisms, redox regulation and clinical implications.  Antioxid Redox Signal. 2008 17 Nov;  , doi: DOI: 10.1089/ARS.2008.2161
  • 108 Anker S D, Chua T P, Ponikowski P. et al . Hormonal changes and catabolic / anabolic imbalance in chronic heart failure and their importance for cardiac cachexia.  Circulation. 1997;  96 526-534
  • 109 Anker S D, Volterrani M, Pflaum C D. et al . Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone.  J Am Coll Cardiol. 2001;  38 443-452
  • 110 Cicoira M, Kalra P R, Anker S D. Growth hormone resistance in chronic heart failure and its therapeutic implications.  J Card Fail. 2003;  9 219-226
  • 111 Isgaard J, Bergh C H, Caidahl K. et al . A placebo-controlled study of growth hormone in patients with congestive heart failure.  Eur Heart J. 1998;  19 1704-1711
  • 112 Osterziel K J, Strohm O, Schuler J. et al . Randomised, double-blind, placebo-controlled trial of human recombinant growth hormone in patients with chronic heart failure due to dilated cardiomyopathy.  Lancet. 1998;  351 1233-1237
  • 113 Houseknecht K L, Baile C A, Matteri R. et al . The biology of leptin: a review.  J Anim Sci. 1998;  76 1405-1420
  • 114 Doehner W, Rauchhaus M, Godsland I F. et al . Insulin resistance in moderate chronic heart failure is related to hyperleptinaemia, but not to norepinephrine or TNF-α.  Int J Cardiol. 2002;  83 73-81
  • 115 Doehner W, Pflaum C D, Rauchhaus M. et al . Leptin, insulin sensitivity and growth hormone binding protein in chronic heart failure with and without cardiac cachexia.  Eur J Endocrinol. 2001;  145 727-735
  • 116 Kennedy A, Gettys T W, Watson P. et al . The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure.  J Clin Endocrinol Metab. 1997;  82 1293-1300
  • 117 Considine R V, Sinha M K, Heiman M L. et al . Serum immunoreactive-leptin concentrations in normal-weight and obese humans.  N Engl J Med. 1996;  334 292-295
  • 118 Tschöp M, Smiley D L, Heiman M L. Ghrelin induces adiposity in rodents.  Nature. 2000;  407 908-913
  • 119 Druce M R, Wren A M, Park A J. et al . Ghrelin increases food intake in obese as well as lean subjects.  Int J Obes (Lond). 2005;  29 1130-1136
  • 120 Tschöp M, Weyer C, Tataranni P A. et al . Circulating ghrelin levels are decreased in human obesity.  Diabetes. 2001;  50 707-709
  • 121 Nagaya N, Uematsu M, Kojima M. et al . Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic / catabolic factors.  Circulation. 2001;  104 2034-2038
  • 122 Vadell C, Seguí M A, Giménez-Arnau J M. et al . Anticachectic efficacy of megestrol acetate at different doses and versus placebo in patients with neoplastic cachexia.  Am J Clin Oncol. 1998;  21 347-351
  • 123 Loprinzi C L, Kugler J W, Sloan J A. et al . Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia / cachexia.  J Clin Oncol. 1999;  17 3299-3306

Dr. med. Stephan von Haehling

Angewandte Kachexieforschung, Medizinische Klinik mit Schwerpunkt Kardiologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum

Augustenburger Platz 1

13353 Berlin

Telefon: +49/30/450553-506

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eMail: stephan.von.haehling@web.de