Skip to main content
Top
Published in: Current Heart Failure Reports 3/2012

01-09-2012 | Decompensated Heart Failure (MM Givertz, Section editor)

Mid-Regional Pro-Adrenomedullin in Acute Heart Failure: A Better Biomarker or Just Another Biomarker?

Authors: Mihael Potocki, Ronny Ziller, Christian Mueller

Published in: Current Heart Failure Reports | Issue 3/2012

Login to get access

Abstract

Circulating biomarkers have become increasingly important in diagnosing and risk-stratifying patients with heart failure (HF). While the natriuretic peptides have received much focus in the past decade, there is increasing interest in the role of other circulating biomarkers such as mid-regional proadrenomedullin (MR-proADM), a stable peptide of the precursor of adrenomedullin (ADM), responsible for volume regulation and electrolyte homeostasis. Increased levels of MR-proADM are associated with an increased risk of mortality and morbidity in patients with HF, independent of natriuretic peptides. MR-proADM outperforms all other established markers in the identification of patients at highest risk of death, particularly death within 30 days. The prognostic superiority has consistently been shown for various cardiovascular disease states, including acute heart failure. In this article, we discuss the potential role of MR-proADM in the syndrome of acute heart failure and its implication on prognosis and risk stratification.
Literature
1.
go back to reference Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95.
2.
go back to reference 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. Rapid measurement of b-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161–7.PubMedCrossRef 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. Rapid measurement of b-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161–7.PubMedCrossRef
3.
go back to reference Januzzi Jr JL, Sakhuja R, O’Donoghue M, Baggish AL, Anwaruddin S, Chae CU, Cameron R, Krauser DG, Tung R, Camargo Jr CA, Lloyd-Jones DM. Utility of amino-terminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department. Arch Intern Med. 2006;166:315–20.PubMedCrossRef Januzzi Jr JL, Sakhuja R, O’Donoghue M, Baggish AL, Anwaruddin S, Chae CU, Cameron R, Krauser DG, Tung R, Camargo Jr CA, Lloyd-Jones DM. Utility of amino-terminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department. Arch Intern Med. 2006;166:315–20.PubMedCrossRef
4.
go back to reference Peacock WFt, De Marco T, Fonarow GC, Diercks D, Wynne J, Apple FS, Wu AH. Cardiac troponin and outcome in acute heart failure. N Engl J Med. 2008;358:2117–26.PubMedCrossRef Peacock WFt, De Marco T, Fonarow GC, Diercks D, Wynne J, Apple FS, Wu AH. Cardiac troponin and outcome in acute heart failure. N Engl J Med. 2008;358:2117–26.PubMedCrossRef
5.
go back to reference Weinberg EO, Shimpo M, Hurwitz S, Tominaga S, Rouleau JL, Lee RT. Identification of serum soluble st2 receptor as a novel heart failure biomarker. Circulation. 2003;107:721–6.PubMedCrossRef Weinberg EO, Shimpo M, Hurwitz S, Tominaga S, Rouleau JL, Lee RT. Identification of serum soluble st2 receptor as a novel heart failure biomarker. Circulation. 2003;107:721–6.PubMedCrossRef
6.
go back to reference Morrow DA, de Lemos JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation. 2007;115:949–52.PubMedCrossRef Morrow DA, de Lemos JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation. 2007;115:949–52.PubMedCrossRef
7.
go back to reference Nakamura M, Yoshida H, Makita S, Arakawa N, Niinuma H, Hiramori K. Potent and long-lasting vasodilatory effects of adrenomedullin in humans. Comparisons between normal subjects and patients with chronic heart failure. Circulation. 1997;95:1214–21.PubMedCrossRef Nakamura M, Yoshida H, Makita S, Arakawa N, Niinuma H, Hiramori K. Potent and long-lasting vasodilatory effects of adrenomedullin in humans. Comparisons between normal subjects and patients with chronic heart failure. Circulation. 1997;95:1214–21.PubMedCrossRef
8.
go back to reference Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Eto T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun. 1993;192:553–60.PubMedCrossRef Kitamura K, Kangawa K, Kawamoto M, Ichiki Y, Nakamura S, Matsuo H, Eto T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun. 1993;192:553–60.PubMedCrossRef
9.
go back to reference Nicholls MG, Charles CJ, Lainchbury JG, Lewis LK, Rademaker MT, Richards AM, Yandle TG. Adrenomedullin in heart failure. Hypertens Res. 2003;26(Suppl):S135–40.PubMedCrossRef Nicholls MG, Charles CJ, Lainchbury JG, Lewis LK, Rademaker MT, Richards AM, Yandle TG. Adrenomedullin in heart failure. Hypertens Res. 2003;26(Suppl):S135–40.PubMedCrossRef
10.
go back to reference Kato J, Kobayashi K, Etoh T, Tanaka M, Kitamura K, Imamura T, Koiwaya Y, Kangawa K, Eto T. Plasma adrenomedullin concentration in patients with heart failure. J Clin Endocrinol Metab. 1996;81:180–3.PubMedCrossRef Kato J, Kobayashi K, Etoh T, Tanaka M, Kitamura K, Imamura T, Koiwaya Y, Kangawa K, Eto T. Plasma adrenomedullin concentration in patients with heart failure. J Clin Endocrinol Metab. 1996;81:180–3.PubMedCrossRef
11.
go back to reference Richards AM, Nicholls MG, Yandle TG, Frampton C, Espiner EA, Turner JG, Buttimore RC, Lainchbury JG, Elliott JM, Ikram H, Crozier IG, Smyth DW. Plasma n-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. Circulation. 1998;97:1921–9.PubMedCrossRef Richards AM, Nicholls MG, Yandle TG, Frampton C, Espiner EA, Turner JG, Buttimore RC, Lainchbury JG, Elliott JM, Ikram H, Crozier IG, Smyth DW. Plasma n-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. Circulation. 1998;97:1921–9.PubMedCrossRef
12.
go back to reference Hinson JP, Kapas S, Smith DM. Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev. 2000;21:138–67.PubMedCrossRef Hinson JP, Kapas S, Smith DM. Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev. 2000;21:138–67.PubMedCrossRef
13.
go back to reference Struck J, Tao C, Morgenthaler NG, Bergmann A. Identification of an adrenomedullin precursor fragment in plasma of sepsis patients. Peptides. 2004;25:1369–72.PubMedCrossRef Struck J, Tao C, Morgenthaler NG, Bergmann A. Identification of an adrenomedullin precursor fragment in plasma of sepsis patients. Peptides. 2004;25:1369–72.PubMedCrossRef
14.
go back to reference Khan SQ, O’Brien RJ, Struck J, Quinn P, Morgenthaler N, Squire I, Davies J, Bergmann A, Ng LL. Prognostic value of midregional pro-adrenomedullin in patients with acute myocardial infarction: the lamp (leicester acute myocardial infarction peptide) study. J Am Coll Cardiol. 2007;49:1525–32.PubMedCrossRef Khan SQ, O’Brien RJ, Struck J, Quinn P, Morgenthaler N, Squire I, Davies J, Bergmann A, Ng LL. Prognostic value of midregional pro-adrenomedullin in patients with acute myocardial infarction: the lamp (leicester acute myocardial infarction peptide) study. J Am Coll Cardiol. 2007;49:1525–32.PubMedCrossRef
15.
go back to reference Gegenhuber A, Struck J, Dieplinger B, Poelz W, Pacher R, Morgenthaler NG, Bergmann A, Haltmayer M, Mueller T. 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.PubMedCrossRef Gegenhuber A, Struck J, Dieplinger B, Poelz W, Pacher R, Morgenthaler NG, Bergmann A, Haltmayer M, Mueller T. 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.PubMedCrossRef
16.
go back to reference Behnes M, Papassotiriou J, Walter T, Fiedler E, Sauer T, Lang S, Elmas E, Hoffmann U, Borggrefe M, Brueckmann M. Long-term prognostic value of mid-regional pro-adrenomedullin and c-terminal pro-endothelin-1 in patients with acute myocardial infarction. Clin Chem Lab Med. 2008;46:204–11.PubMedCrossRef Behnes M, Papassotiriou J, Walter T, Fiedler E, Sauer T, Lang S, Elmas E, Hoffmann U, Borggrefe M, Brueckmann M. Long-term prognostic value of mid-regional pro-adrenomedullin and c-terminal pro-endothelin-1 in patients with acute myocardial infarction. Clin Chem Lab Med. 2008;46:204–11.PubMedCrossRef
17.
go back to reference Adlbrecht C, Hulsmann M, Strunk G, Berger R, Mortl D, Struck J, Morgenthaler NG, Bergmann A, Jakowitsch J, Maurer G, Lang IM, Pacher R. Prognostic value of plasma midregional pro-adrenomedullin and c-terminal-pro-endothelin-1 in chronic heart failure outpatients. Eur J Heart Fail. 2009;11:361–6.PubMedCrossRef Adlbrecht C, Hulsmann M, Strunk G, Berger R, Mortl D, Struck J, Morgenthaler NG, Bergmann A, Jakowitsch J, Maurer G, Lang IM, Pacher R. Prognostic value of plasma midregional pro-adrenomedullin and c-terminal-pro-endothelin-1 in chronic heart failure outpatients. Eur J Heart Fail. 2009;11:361–6.PubMedCrossRef
18.
go back to reference Gombos T, Forhecz Z, Pozsonyi Z, Wallentin S, Papassotiriou J, Kunde J, Morgenthaler NG, Janoskuti L, Prohaszka Z. Adrenomedullin and endothelin-1 are related to inflammation in chronic heart failure. Inflamm Res. 2009;58:298–305.PubMedCrossRef Gombos T, Forhecz Z, Pozsonyi Z, Wallentin S, Papassotiriou J, Kunde J, Morgenthaler NG, Janoskuti L, Prohaszka Z. Adrenomedullin and endothelin-1 are related to inflammation in chronic heart failure. Inflamm Res. 2009;58:298–305.PubMedCrossRef
19.
go back to reference Potocki M, Breidthardt T, Reichlin T, Morgenthaler NG, Bergmann A, Noveanu M, Schaub N, Uthoff H, Freidank H, Buser L, Bingisser R, Christ M, Mebazaa A, Mueller C. Midregional pro-adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study. Crit Care. 2009;13:R122.PubMedCrossRef Potocki M, Breidthardt T, Reichlin T, Morgenthaler NG, Bergmann A, Noveanu M, Schaub N, Uthoff H, Freidank H, Buser L, Bingisser R, Christ M, Mebazaa A, Mueller C. Midregional pro-adrenomedullin in addition to b-type natriuretic peptides in the risk stratification of patients with acute dyspnea: an observational study. Crit Care. 2009;13:R122.PubMedCrossRef
20.
go back to reference Masson S, Latini R, Carbonieri E, Moretti L, Rossi MG, Ciricugno S, Milani V, Marchioli R, Struck J, Bergmann A, Maggioni AP, Tognoni G, Tavazzi L, Investigators G-H. The predictive value of stable precursor fragments of vasoactive peptides in patients with chronic heart failure: data from the gissi-heart failure (gissi-hf) trial. Eur J Heart Fail. 2010;12:338–47.PubMedCrossRef Masson S, Latini R, Carbonieri E, Moretti L, Rossi MG, Ciricugno S, Milani V, Marchioli R, Struck J, Bergmann A, Maggioni AP, Tognoni G, Tavazzi L, Investigators G-H. The predictive value of stable precursor fragments of vasoactive peptides in patients with chronic heart failure: data from the gissi-heart failure (gissi-hf) trial. Eur J Heart Fail. 2010;12:338–47.PubMedCrossRef
21.
go back to reference von Haehling S, Filippatos GS, Papassotiriou J, Cicoira M, Jankowska EA, Doehner W, Rozentryt P, Vassanelli C, Struck J, Banasiak W, Ponikowski P, Kremastinos D, Bergmann A, Morgenthaler NG, Anker SD. Mid-regional pro-adrenomedullin as a novel predictor of mortality in patients with chronic heart failure. Eur J Heart Fail. 2010;12:484–91.CrossRef von Haehling S, Filippatos GS, Papassotiriou J, Cicoira M, Jankowska EA, Doehner W, Rozentryt P, Vassanelli C, Struck J, Banasiak W, Ponikowski P, Kremastinos D, Bergmann A, Morgenthaler NG, Anker SD. Mid-regional pro-adrenomedullin as a novel predictor of mortality in patients with chronic heart failure. Eur J Heart Fail. 2010;12:484–91.CrossRef
22.
go back to reference Klip IT, Voors AA, Anker SD, Hillege HL, Struck J, Squire I, van Veldhuisen DJ, Dickstein K, OPTIMAAL Investigators. Prognostic value of mid-regional pro-adrenomedullin in patients with heart failure after an acute myocardial infarction. Heart. 2011;97:892–8. Klip IT, Voors AA, Anker SD, Hillege HL, Struck J, Squire I, van Veldhuisen DJ, Dickstein K, OPTIMAAL Investigators. Prognostic value of mid-regional pro-adrenomedullin in patients with heart failure after an acute myocardial infarction. Heart. 2011;97:892–8.
23.
go back to reference •• Maisel A, Mueller C, Nowak RM, Peacock WF, Ponikowski P, Mockel M, Hogan C, Wu AH, Richards M, Clopton P, Filippatos GS, Di Somma S, Anand I, Ng LL, Daniels LB, Neath SX, Christenson R, Potocki M, McCord J, Hartmann O, Morgenthaler NG, Anker SD. 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. This prospective, multicenter, international study included 1,641 patients presenting to the emergency department with dyspnea. In the subgroup of 568 patients diagnosed with acute heart failure, MR-proADM was superior to BNP and NT-proBNP for predicting 90-day mortality and especially 30-day mortality.PubMedCrossRef •• Maisel A, Mueller C, Nowak RM, Peacock WF, Ponikowski P, Mockel M, Hogan C, Wu AH, Richards M, Clopton P, Filippatos GS, Di Somma S, Anand I, Ng LL, Daniels LB, Neath SX, Christenson R, Potocki M, McCord J, Hartmann O, Morgenthaler NG, Anker SD. 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. This prospective, multicenter, international study included 1,641 patients presenting to the emergency department with dyspnea. In the subgroup of 568 patients diagnosed with acute heart failure, MR-proADM was superior to BNP and NT-proBNP for predicting 90-day mortality and especially 30-day mortality.PubMedCrossRef
24.
go back to reference Peacock WF, Nowak R, Christenson R, DiSomma S, Neath SX, Hartmann O, Mueller C, Ponikowski P, Mockel M, Hogan C, Wu AH, Richards M, Filippatos GS, Anand I, Ng LL, Daniels LB, Morgenthaler N, Anker SD, Maisel AS. Short-term mortality risk in emergency department acute heart failure. Acad Emerg Med. 2011;18:947–58.PubMedCrossRef Peacock WF, Nowak R, Christenson R, DiSomma S, Neath SX, Hartmann O, Mueller C, Ponikowski P, Mockel M, Hogan C, Wu AH, Richards M, Filippatos GS, Anand I, Ng LL, Daniels LB, Morgenthaler N, Anker SD, Maisel AS. Short-term mortality risk in emergency department acute heart failure. Acad Emerg Med. 2011;18:947–58.PubMedCrossRef
25.
go back to reference Maisel A, Mueller C, Nowak R, Peacock WF, Landsberg JW, Ponikowski P, Mockel M, Hogan C, Wu AH, Richards M, Clopton P, Filippatos GS, Di Somma S, Anand I, Ng L, Daniels LB, Neath SX, Christenson R, Potocki M, McCord J, Terracciano G, Kremastinos D, Hartmann O, von Haehling S, Bergmann A, Morgenthaler NG, Anker SD. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the bach (biomarkers in acute heart failure) trial. J Am Coll Cardiol. 2010;55:2062–76.PubMedCrossRef Maisel A, Mueller C, Nowak R, Peacock WF, Landsberg JW, Ponikowski P, Mockel M, Hogan C, Wu AH, Richards M, Clopton P, Filippatos GS, Di Somma S, Anand I, Ng L, Daniels LB, Neath SX, Christenson R, Potocki M, McCord J, Terracciano G, Kremastinos D, Hartmann O, von Haehling S, Bergmann A, Morgenthaler NG, Anker SD. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the bach (biomarkers in acute heart failure) trial. J Am Coll Cardiol. 2010;55:2062–76.PubMedCrossRef
26.
27.
go back to reference Kitamura K, Kangawa K, Ishiyama Y, Washimine H, Ichiki Y, Kawamoto M, Minamino N, Matsuo H, Eto T. Identification and hypotensive activity of proadrenomedullin n-terminal 20 peptide (pamp). FEBS Lett. 1994;351:35–7.PubMedCrossRef Kitamura K, Kangawa K, Ishiyama Y, Washimine H, Ichiki Y, Kawamoto M, Minamino N, Matsuo H, Eto T. Identification and hypotensive activity of proadrenomedullin n-terminal 20 peptide (pamp). FEBS Lett. 1994;351:35–7.PubMedCrossRef
28.
go back to reference Watanabe TX, Itahara Y, Inui T, Yoshizawa-Kumagaye K, Nakajima K, Sakakibara S. Vasopressor activities of n-terminal fragments of adrenomedullin in anesthetized rat. Biochem Biophys Res Commun. 1996;219:59–63.PubMedCrossRef Watanabe TX, Itahara Y, Inui T, Yoshizawa-Kumagaye K, Nakajima K, Sakakibara S. Vasopressor activities of n-terminal fragments of adrenomedullin in anesthetized rat. Biochem Biophys Res Commun. 1996;219:59–63.PubMedCrossRef
29.
go back to reference Gumusel B, Hao Q, Hyman AL, Kadowitz PJ, Champion HC, Chang JK, Mehta JL, Lippton H. Analysis of responses to adrenomedullin-(13–52) in the pulmonary vascular bed of rats. Am J Physiol. 1998;274:H1255–63.PubMed Gumusel B, Hao Q, Hyman AL, Kadowitz PJ, Champion HC, Chang JK, Mehta JL, Lippton H. Analysis of responses to adrenomedullin-(13–52) in the pulmonary vascular bed of rats. Am J Physiol. 1998;274:H1255–63.PubMed
30.
go back to reference Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, Foord SM. International union of pharmacology. Xxxii. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev. 2002;54:233–46.PubMedCrossRef Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, Foord SM. International union of pharmacology. Xxxii. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev. 2002;54:233–46.PubMedCrossRef
31.
go back to reference Lopez J, Martinez A. Cell and molecular biology of the multifunctional peptide, adrenomedullin. Int Rev Cytol. 2002;221:1–92.PubMedCrossRef Lopez J, Martinez A. Cell and molecular biology of the multifunctional peptide, adrenomedullin. Int Rev Cytol. 2002;221:1–92.PubMedCrossRef
32.
go back to reference Tomoda Y, Isumi Y, Katafuchi T, Minamino N. Regulation of adrenomedullin secretion from cultured cells. Peptides. 2001;22:1783–94.PubMedCrossRef Tomoda Y, Isumi Y, Katafuchi T, Minamino N. Regulation of adrenomedullin secretion from cultured cells. Peptides. 2001;22:1783–94.PubMedCrossRef
33.
go back to reference Zhou M, Chaudry IH, Wang P. The small intestine is an important source of adrenomedullin release during polymicrobial sepsis. Am J Physiol Regul Integr Comp Physiol. 2001;281:R654–60.PubMed Zhou M, Chaudry IH, Wang P. The small intestine is an important source of adrenomedullin release during polymicrobial sepsis. Am J Physiol Regul Integr Comp Physiol. 2001;281:R654–60.PubMed
34.
go back to reference Zhou M, Chaudry IH, Wang P. Adrenomedullin is upregulated in the heart and aorta during the early and late stages of sepsis. Biochim Biophys Acta. 1999;1453:273–83.PubMedCrossRef Zhou M, Chaudry IH, Wang P. Adrenomedullin is upregulated in the heart and aorta during the early and late stages of sepsis. Biochim Biophys Acta. 1999;1453:273–83.PubMedCrossRef
35.
go back to reference Washimine H, Asada Y, Kitamura K, Ichiki Y, Hara S, Yamamoto Y, Kangawa K, Sumiyoshi A, Eto T. Immunohistochemical identification of adrenomedullin in human, rat, and porcine tissue. Histochem Cell Biol. 1995;103:251–4.PubMedCrossRef Washimine H, Asada Y, Kitamura K, Ichiki Y, Hara S, Yamamoto Y, Kangawa K, Sumiyoshi A, Eto T. Immunohistochemical identification of adrenomedullin in human, rat, and porcine tissue. Histochem Cell Biol. 1995;103:251–4.PubMedCrossRef
36.
go back to reference Ishimitsu T, Miyata A, Matsuoka H, Kangawa K. Transcriptional regulation of human adrenomedullin gene in vascular endothelial cells. Biochem Biophys Res Commun. 1998;243:463–70.PubMedCrossRef Ishimitsu T, Miyata A, Matsuoka H, Kangawa K. Transcriptional regulation of human adrenomedullin gene in vascular endothelial cells. Biochem Biophys Res Commun. 1998;243:463–70.PubMedCrossRef
37.
go back to reference Sugo S, Minamino N, Kangawa K, Miyamoto K, Kitamura K, Sakata J, Eto T, Matsuo H. Endothelial cells actively synthesize and secrete adrenomedullin. Biochem Biophys Res Commun. 1994;201:1160–6.PubMedCrossRef Sugo S, Minamino N, Kangawa K, Miyamoto K, Kitamura K, Sakata J, Eto T, Matsuo H. Endothelial cells actively synthesize and secrete adrenomedullin. Biochem Biophys Res Commun. 1994;201:1160–6.PubMedCrossRef
38.
go back to reference Meeran K, O’Shea D, Upton PD, Small CJ, Ghatei MA, Byfield PH, Bloom SR. 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.PubMedCrossRef Meeran K, O’Shea D, Upton PD, Small CJ, Ghatei MA, Byfield PH, Bloom SR. 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.PubMedCrossRef
39.
go back to reference Lewis LK, Smith MW, Yandle TG, Richards AM, Nicholls MG. Adrenomedullin(1–52) measured in human plasma by radioimmunoassay: plasma concentration, adsorption, and storage. Clin Chem. 1998;44:571–7.PubMed Lewis LK, Smith MW, Yandle TG, Richards AM, Nicholls MG. Adrenomedullin(1–52) measured in human plasma by radioimmunoassay: plasma concentration, adsorption, and storage. Clin Chem. 1998;44:571–7.PubMed
40.
go back to reference Morgenthaler NG, Struck J, Alonso C, Bergmann A. Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay. Clin Chem. 2005;51:1823–9.PubMedCrossRef Morgenthaler NG, Struck J, Alonso C, Bergmann A. Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay. Clin Chem. 2005;51:1823–9.PubMedCrossRef
41.
go back to reference Ishiyama Y, Kitamura K, Ichiki Y, Nakamura S, Kida O, Kangawa K, Eto T. Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats. Eur J Pharmacol. 1993;241:271–3.PubMedCrossRef Ishiyama Y, Kitamura K, Ichiki Y, Nakamura S, Kida O, Kangawa K, Eto T. Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats. Eur J Pharmacol. 1993;241:271–3.PubMedCrossRef
42.
go back to reference Jougasaki M, Stevens TL, Borgeson DD, Luchner A, Redfield MM, Burnett Jr JC. Adrenomedullin in experimental congestive heart failure: cardiorenal activation. Am J Physiol. 1997;273:R1392–9.PubMed Jougasaki M, Stevens TL, Borgeson DD, Luchner A, Redfield MM, Burnett Jr JC. Adrenomedullin in experimental congestive heart failure: cardiorenal activation. Am J Physiol. 1997;273:R1392–9.PubMed
43.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
44.
go back to reference Tsuruda T, Kato J, Kitamura K, Kuwasako K, Imamura T, Koiwaya Y, Kangawa K, Eto T. Secretion of proadrenomedullin n-terminal 20 peptide from cultured neonatal rat cardiac cells. Life Sci. 2001;69:239–45.PubMedCrossRef Tsuruda T, Kato J, Kitamura K, Kuwasako K, Imamura T, Koiwaya Y, Kangawa K, Eto T. Secretion of proadrenomedullin n-terminal 20 peptide from cultured neonatal rat cardiac cells. Life Sci. 2001;69:239–45.PubMedCrossRef
45.
go back to reference Chun TH, Itoh H, Saito T, Yamahara K, Doi K, Mori Y, Ogawa Y, Yamashita J, Tanaka T, Inoue M, Masatsugu K, Sawada N, Fukunaga Y, Nakao K. Oxidative stress augments secretion of endothelium-derived relaxing peptides, c-type natriuretic peptide and adrenomedullin. J Hypertens. 2000;18:575–80.PubMedCrossRef Chun TH, Itoh H, Saito T, Yamahara K, Doi K, Mori Y, Ogawa Y, Yamashita J, Tanaka T, Inoue M, Masatsugu K, Sawada N, Fukunaga Y, Nakao K. Oxidative stress augments secretion of endothelium-derived relaxing peptides, c-type natriuretic peptide and adrenomedullin. J Hypertens. 2000;18:575–80.PubMedCrossRef
46.
go back to reference Chun TH, Itoh H, Ogawa Y, Tamura N, Takaya K, Igaki T, Yamashita J, Doi K, Inoue M, Masatsugu K, Korenaga R, Ando J, Nakao K. Shear stress augments expression of c-type natriuretic peptide and adrenomedullin. Hypertension. 1997;29:1296–302.PubMedCrossRef Chun TH, Itoh H, Ogawa Y, Tamura N, Takaya K, Igaki T, Yamashita J, Doi K, Inoue M, Masatsugu K, Korenaga R, Ando J, Nakao K. Shear stress augments expression of c-type natriuretic peptide and adrenomedullin. Hypertension. 1997;29:1296–302.PubMedCrossRef
47.
go back to reference Cormier-Regard S, Nguyen SV, Claycomb WC. Adrenomedullin gene expression is developmentally regulated and induced by hypoxia in rat ventricular cardiac myocytes. J Biol Chem. 1998;273:17787–92.PubMedCrossRef Cormier-Regard S, Nguyen SV, Claycomb WC. Adrenomedullin gene expression is developmentally regulated and induced by hypoxia in rat ventricular cardiac myocytes. J Biol Chem. 1998;273:17787–92.PubMedCrossRef
48.
go back to reference Nishikimi T, Yoshihara F, Mori Y, Kangawa K, Matsuoka H. Cardioprotective effect of adrenomedullin in heart failure. Hypertens Res. 2003;26(Suppl):S121–7.PubMedCrossRef Nishikimi T, Yoshihara F, Mori Y, Kangawa K, Matsuoka H. Cardioprotective effect of adrenomedullin in heart failure. Hypertens Res. 2003;26(Suppl):S121–7.PubMedCrossRef
49.
go back to reference Hirata Y, Hayakawa H, Suzuki Y, Suzuki E, Ikenouchi H, Kohmoto O, Kimura K, Kitamura K, Eto T, Kangawa K, et al. Mechanisms of adrenomedullin-induced vasodilation in the rat kidney. Hypertension. 1995;25:790–5.PubMedCrossRef Hirata Y, Hayakawa H, Suzuki Y, Suzuki E, Ikenouchi H, Kohmoto O, Kimura K, Kitamura K, Eto T, Kangawa K, et al. Mechanisms of adrenomedullin-induced vasodilation in the rat kidney. Hypertension. 1995;25:790–5.PubMedCrossRef
50.
go back to reference Tsuruda T, Kato J, Kitamura K, Kuwasako K, Imamura T, Koiwaya Y, Tsuji T, Kangawa K, Eto T. Adrenomedullin: a possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes. Hypertension. 1998;31:505–10.PubMedCrossRef Tsuruda T, Kato J, Kitamura K, Kuwasako K, Imamura T, Koiwaya Y, Tsuji T, Kangawa K, Eto T. Adrenomedullin: a possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes. Hypertension. 1998;31:505–10.PubMedCrossRef
51.
go back to reference Inatsu H, Sakata J, Shimokubo T, Kitani M, Nishizono M, Washimine H, Kitamura K, Kangawa K, Matsuo H, Eto T. Distribution and characterization of rat immunoreactive proadrenomedullin n-terminal 20 peptide (pamp) and the augmented cardiac pamp in spontaneously hypertensive rat. Biochem Mol Biol Int. 1996;38:365–72.PubMed Inatsu H, Sakata J, Shimokubo T, Kitani M, Nishizono M, Washimine H, Kitamura K, Kangawa K, Matsuo H, Eto T. Distribution and characterization of rat immunoreactive proadrenomedullin n-terminal 20 peptide (pamp) and the augmented cardiac pamp in spontaneously hypertensive rat. Biochem Mol Biol Int. 1996;38:365–72.PubMed
52.
go back to reference Romppanen H, Marttila M, Magga J, Vuolteenaho O, Kinnunen P, Szokodi I, Ruskoaho H. Adrenomedullin gene expression in the rat heart is stimulated by acute pressure overload: blunted effect in experimental hypertension. Endocrinology. 1997;138:2636–9.PubMedCrossRef Romppanen H, Marttila M, Magga J, Vuolteenaho O, Kinnunen P, Szokodi I, Ruskoaho H. Adrenomedullin gene expression in the rat heart is stimulated by acute pressure overload: blunted effect in experimental hypertension. Endocrinology. 1997;138:2636–9.PubMedCrossRef
53.
go back to reference Nishikimi T, Horio T, Sasaki T, Yoshihara F, Takishita S, Miyata A, Matsuo H, Kangawa K. Cardiac production and secretion of adrenomedullin are increased in heart failure. Hypertension. 1997;30:1369–75.PubMedCrossRef Nishikimi T, Horio T, Sasaki T, Yoshihara F, Takishita S, Miyata A, Matsuo H, Kangawa K. Cardiac production and secretion of adrenomedullin are increased in heart failure. Hypertension. 1997;30:1369–75.PubMedCrossRef
54.
go back to reference Niu P, Shindo T, Iwata H, Iimuro S, Takeda N, Zhang Y, Ebihara A, Suematsu Y, Kangawa K, Hirata Y, Nagai R. Protective effects of endogenous adrenomedullin on cardiac hypertrophy, fibrosis, and renal damage. Circulation. 2004;109:1789–94.PubMedCrossRef Niu P, Shindo T, Iwata H, Iimuro S, Takeda N, Zhang Y, Ebihara A, Suematsu Y, Kangawa K, Hirata Y, Nagai R. Protective effects of endogenous adrenomedullin on cardiac hypertrophy, fibrosis, and renal damage. Circulation. 2004;109:1789–94.PubMedCrossRef
55.
go back to reference Kawai J, Ando K, Tojo A, Shimosawa T, Takahashi K, Onozato ML, Yamasaki M, Ogita T, Nakaoka T, Fujita T. Endogenous adrenomedullin protects against vascular response to injury in mice. Circulation. 2004;109:1147–53.PubMedCrossRef Kawai J, Ando K, Tojo A, Shimosawa T, Takahashi K, Onozato ML, Yamasaki M, Ogita T, Nakaoka T, Fujita T. Endogenous adrenomedullin protects against vascular response to injury in mice. Circulation. 2004;109:1147–53.PubMedCrossRef
56.
go back to reference Jougasaki M, Wei CM, McKinley LJ, Burnett Jr JC. Elevation of circulating and ventricular adrenomedullin in human congestive heart failure. Circulation. 1995;92:286–9.PubMedCrossRef Jougasaki M, Wei CM, McKinley LJ, Burnett Jr JC. Elevation of circulating and ventricular adrenomedullin in human congestive heart failure. Circulation. 1995;92:286–9.PubMedCrossRef
57.
go back to reference Hamada M, Shigematsu Y, Kawakami H, Minamino N, Kangawa K, Matsuo H, Hiwada K. Increased plasma levels of adrenomedullin in patients with hypertrophic cardiomyopathy: its relation to endothelin-i, natriuretic peptides and noradrenaline. Clin Sci (Lond). 1998;94:21–8. Hamada M, Shigematsu Y, Kawakami H, Minamino N, Kangawa K, Matsuo H, Hiwada K. Increased plasma levels of adrenomedullin in patients with hypertrophic cardiomyopathy: its relation to endothelin-i, natriuretic peptides and noradrenaline. Clin Sci (Lond). 1998;94:21–8.
58.
go back to reference Lainchbury JG, Cooper GJ, Coy DH, Jiang NY, Lewis LK, Yandle TG, Richards AM, Nicholls MG. Adrenomedullin: a hypotensive hormone in man. Clin Sci (Lond). 1997;92:467–72. Lainchbury JG, Cooper GJ, Coy DH, Jiang NY, Lewis LK, Yandle TG, Richards AM, Nicholls MG. Adrenomedullin: a hypotensive hormone in man. Clin Sci (Lond). 1997;92:467–72.
59.
go back to reference Nagaya N, Satoh T, Nishikimi T, Uematsu M, Furuichi S, Sakamaki F, Oya H, Kyotani S, Nakanishi N, Goto Y, Masuda Y, Miyatake K, Kangawa K. Hemodynamic, renal, and hormonal effects of adrenomedullin infusion in patients with congestive heart failure. Circulation. 2000;101:498–503.PubMedCrossRef Nagaya N, Satoh T, Nishikimi T, Uematsu M, Furuichi S, Sakamaki F, Oya H, Kyotani S, Nakanishi N, Goto Y, Masuda Y, Miyatake K, Kangawa K. Hemodynamic, renal, and hormonal effects of adrenomedullin infusion in patients with congestive heart failure. Circulation. 2000;101:498–503.PubMedCrossRef
60.
go back to reference Bhandari SS, Davies JE, Struck J, Ng LL. Influence of confounding factors on plasma mid-regional pro-adrenomedullin and mid-regional pro-a-type natriuretic peptide concentrations in healthy individuals. Biomarkers. 2011;16:281–7.PubMedCrossRef Bhandari SS, Davies JE, Struck J, Ng LL. Influence of confounding factors on plasma mid-regional pro-adrenomedullin and mid-regional pro-a-type natriuretic peptide concentrations in healthy individuals. Biomarkers. 2011;16:281–7.PubMedCrossRef
61.
go back to reference Li Y, Jiang C, Wang X, Zhang Y, Shibahara S, Takahashi K. Adrenomedullin is a novel adipokine: adrenomedullin in adipocytes and adipose tissues. Peptides. 2007;28:1129–43.PubMedCrossRef Li Y, Jiang C, Wang X, Zhang Y, Shibahara S, Takahashi K. Adrenomedullin is a novel adipokine: adrenomedullin in adipocytes and adipose tissues. Peptides. 2007;28:1129–43.PubMedCrossRef
62.
go back to reference Shimosawa T, Ogihara T, Matsui H, Asano T, Ando K, Fujita T. Deficiency of adrenomedullin induces insulin resistance by increasing oxidative stress. Hypertension. 2003;41:1080–5.PubMedCrossRef Shimosawa T, Ogihara T, Matsui H, Asano T, Ando K, Fujita T. Deficiency of adrenomedullin induces insulin resistance by increasing oxidative stress. Hypertension. 2003;41:1080–5.PubMedCrossRef
63.
go back to reference Dieplinger B, Mueller T, Kollerits B, Struck J, Ritz E, von Eckardstein A, Haltmayer M, Kronenberg F, Group MS. Pro-a-type natriuretic peptide and pro-adrenomedullin predict progression of chronic kidney disease: the mmkd study. Kidney Int. 2009;75:408–14.PubMedCrossRef Dieplinger B, Mueller T, Kollerits B, Struck J, Ritz E, von Eckardstein A, Haltmayer M, Kronenberg F, Group MS. Pro-a-type natriuretic peptide and pro-adrenomedullin predict progression of chronic kidney disease: the mmkd study. Kidney Int. 2009;75:408–14.PubMedCrossRef
64.
go back to reference Richards AM, Nicholls MG, Espiner EA, Lainchbury JG, Troughton RW, Elliott J, Frampton C, Turner J, Crozier IG, Yandle TG. B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation. 2003;107:2786–92.PubMedCrossRef Richards AM, Nicholls MG, Espiner EA, Lainchbury JG, Troughton RW, Elliott J, Frampton C, Turner J, Crozier IG, Yandle TG. B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation. 2003;107:2786–92.PubMedCrossRef
65.
go back to reference Heeschen C, Hamm CW, Mitrovic V, Lantelme NH, White HD. N-terminal pro-b-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes. Circulation. 2004;110:3206–12.PubMedCrossRef Heeschen C, Hamm CW, Mitrovic V, Lantelme NH, White HD. N-terminal pro-b-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes. Circulation. 2004;110:3206–12.PubMedCrossRef
66.
go back to reference Morrow DA, de Lemos JA, Sabatine MS, Murphy SA, Demopoulos LA, DiBattiste PM, McCabe CH, Gibson CM, Cannon CP, Braunwald E. Evaluation of b-type natriuretic peptide for risk assessment in unstable angina/non-st-elevation myocardial infarction: B-type natriuretic peptide and prognosis in tactics-timi 18. J Am Coll Cardiol. 2003;41:1264–72.PubMedCrossRef Morrow DA, de Lemos JA, Sabatine MS, Murphy SA, Demopoulos LA, DiBattiste PM, McCabe CH, Gibson CM, Cannon CP, Braunwald E. Evaluation of b-type natriuretic peptide for risk assessment in unstable angina/non-st-elevation myocardial infarction: B-type natriuretic peptide and prognosis in tactics-timi 18. J Am Coll Cardiol. 2003;41:1264–72.PubMedCrossRef
67.
go back to reference Wild PS, Schnabel RB, Lubos E, Zeller T, Sinning CR, Keller T, Tzikas S, Lackner KJ, Peetz D, Rupprecht HJ, Bickel C, Morgenthaler NG, Papassotiriou J, Tiret L, Munzel T, Blankenberg S. Midregional proadrenomedullin for prediction of cardiovascular events in coronary artery disease: results from the atherogene study. Clin Chem. 2012;58:226–36.PubMedCrossRef Wild PS, Schnabel RB, Lubos E, Zeller T, Sinning CR, Keller T, Tzikas S, Lackner KJ, Peetz D, Rupprecht HJ, Bickel C, Morgenthaler NG, Papassotiriou J, Tiret L, Munzel T, Blankenberg S. Midregional proadrenomedullin for prediction of cardiovascular events in coronary artery disease: results from the atherogene study. Clin Chem. 2012;58:226–36.PubMedCrossRef
68.
go back to reference Nishikimi T, Saito Y, Kitamura K, Ishimitsu T, Eto T, Kangawa K, Matsuo H, Omae T, Matsuoka H. Increased plasma levels of adrenomedullin in patients with heart failure. J Am Coll Cardiol. 1995;26:1424–31.PubMedCrossRef Nishikimi T, Saito Y, Kitamura K, Ishimitsu T, Eto T, Kangawa K, Matsuo H, Omae T, Matsuoka H. Increased plasma levels of adrenomedullin in patients with heart failure. J Am Coll Cardiol. 1995;26:1424–31.PubMedCrossRef
69.
go back to reference Richards AM, Doughty R, Nicholls MG, MacMahon S, Sharpe N, Murphy J, Espiner EA, Frampton C, Yandle TG. 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. 2001;37:1781–7.PubMedCrossRef Richards AM, Doughty R, Nicholls MG, MacMahon S, Sharpe N, Murphy J, Espiner EA, Frampton C, Yandle TG. 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. 2001;37:1781–7.PubMedCrossRef
70.
go back to reference Pousset F, Masson F, Chavirovskaia O, Isnard R, Carayon A, Golmard JL, Lechat P, Thomas D, Komajda M. Plasma adrenomedullin, a new independent predictor of prognosis in patients with chronic heart failure. Eur Heart J. 2000;21:1009–14.PubMedCrossRef Pousset F, Masson F, Chavirovskaia O, Isnard R, Carayon A, Golmard JL, Lechat P, Thomas D, Komajda M. Plasma adrenomedullin, a new independent predictor of prognosis in patients with chronic heart failure. Eur Heart J. 2000;21:1009–14.PubMedCrossRef
71.
go back to reference Lee DS, Schull MJ, Alter DA, Austin PC, Laupacis A, Chong A, Tu JV, Stukel TA. Early deaths in patients with heart failure discharged from the emergency department: a population-based analysis. Circ Heart Fail. 2010;3:228–35.PubMedCrossRef Lee DS, Schull MJ, Alter DA, Austin PC, Laupacis A, Chong A, Tu JV, Stukel TA. Early deaths in patients with heart failure discharged from the emergency department: a population-based analysis. Circ Heart Fail. 2010;3:228–35.PubMedCrossRef
Metadata
Title
Mid-Regional Pro-Adrenomedullin in Acute Heart Failure: A Better Biomarker or Just Another Biomarker?
Authors
Mihael Potocki
Ronny Ziller
Christian Mueller
Publication date
01-09-2012
Publisher
Current Science Inc.
Published in
Current Heart Failure Reports / Issue 3/2012
Print ISSN: 1546-9530
Electronic ISSN: 1546-9549
DOI
https://doi.org/10.1007/s11897-012-0096-6

Other articles of this Issue 3/2012

Current Heart Failure Reports 3/2012 Go to the issue

Investigative Therapies (J.-L. Balligand, Section editor)

AMP-activated Protein Kinase in the Control of Cardiac Metabolism and Remodeling

Investigative Therapies (J.-L. Balligand, Section editor)

New Treatment Options for Late Na Current, Arrhythmias, and Diastolic Dysfunction

Investigative Therapies (J.-L. Balligand, Section editor)

Cardiac Side Effects of Anticancer Treatments: New Mechanistic Insights

Decompensated Heart Failure (MM Givertz, Section editor)

Management of Acute Right Ventricular Failure in the Intensive Care Unit