Evaluation of MR-proADM and Copeptin Levels in Dogs with Heart Disease
Résumé
The measurement of copeptin and MR-proADM for the detection of cardiac dysfunction in humans has come to the fore in recent years. Although troponin and NT-proBNP have been extensively studied, copeptin and MR-proADM have not been studied in dogs. In this study, copeptin and MR-proADM levels were examined in dogs with heart disease. The study included groups B1 (n=15), B2 (n=13) and C (n=22), which were diagnosed with heart disease and classified according to ACVIM, and the control group (n=20), which was classified as healthy (group A). Blood count, biochemistry, electrolyte values, electrocardiographic and echocardiographic findings as well as serum levels of troponin I, troponin T, NT-proBNP, copeptin and MR-proADM were evaluated. In this study, copeptin levels were 71.12±30.06 ng/L in the control group, 85.88±26.25 ng/L in the B1 group, 113.35±36.07 ng/L in the B2 group and 344.63±453 ng/L in the C group. The MR-proADM values were 10.91±5.77 in the control group, 13.55±5.41 ng/L in B1, 14.16±3.94 ng/L in B2 and 54.72±88.89 ng/L in the C group. The increase in copeptin and troponin T in groups B2 and C and in MR-proADM, NT-proBNP and troponin I in group C proved to be statistically significant (p <0.05). The values of troponin T and MR-proADM were moderately negatively correlated in group B2 (r=59.7%), while the values of troponin I and copeptin were moderately positively correlated in group C (r=44.6%). Furthermore, in group C, copeptin and MR-proADM values were more positively correlated than average (r=68.6%). Similar to human studies, copeptin and MR-proADM were significantly elevated in dogs with advanced heart disease. Copeptin and MR-proADM biomarkers can be used in conjunction with other cardiac biomarkers.
Article Details
- Comment citer
-
Gonul, R., & Sağoğlu, H. (2025). Evaluation of MR-proADM and Copeptin Levels in Dogs with Heart Disease. Journal of the Hellenic Veterinary Medical Society, 76(2), 9097–9106. https://doi.org/10.12681/jhvms.36886
- Numéro
- Vol. 76 No 2 (2025)
- Rubrique
- Research Articles
Ce travail est disponible sous licence Creative Commons Attribution - Pas d’Utilisation Commerciale 4.0 International.
Authors who publish with this journal agree to the following terms:
· Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution Non-Commercial License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
· Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g. post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
· Authors are permitted and encouraged to post their work online (preferably in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
Téléchargements
Les données relatives au téléchargement ne sont pas encore disponibles.
Références
Balling L, Goetze JP, Jung MH, Rossing K, Boesgaard S, Gustafsson F
(2018) Copeptin levels and invasive hemodynamics in patients with
advanced heart failure. Biomark Med 12 (8):861–870.
Betowski J, Jamroz A (2004) Adrenomedullin–what do we know 10
years since its discovery? Pol J Pharmacol 56 (1):5-27.
Bioassay Technology Laboratory (2024) https://www.bt-laboratory.com
[acessed 19 July 2024}.
Bonagura D, Schober KE (2009) Can ventricular function be assessed
byechocardiography in chronic caninemitral valve disease? J Small
anim Pract 50 (1): 12–24.
Boon JA (2011) Veterinary Echocardiography. John Wiley & Sons:
Hoboken, NJ, USA.
Borgarelli M, Crosara S, Lamb K, Savarino P, La Rosa G, Tarducci
A, Haggstrom J (2012) Survival Characteristics and Prognostic
Variables of Dogs with Preclinical Chronic Degenerative Mitral
Valve Disease Attributable to Myxomatous Degeneration. J Vet
Intern Med 26 (1):69–75.
Borgarelli M, Abbott J, Braz-Ruivo L, Chiavegato D, Crosara S, Lamb
K, Ljungvall I, Poggi M, Santilli RA, Haggstrom J (2015) Prevalence
and prognostic importance of pulmonary hypertension in
dogs with myxomatous mitral valve disease. J Vet Intern Med
(2):569-574.
Buchanan JW, Bücheler J (1995) Vertebral scale system to measure canine
heart size in radiographs. JAm Vet Med Assoc 206 (2):194-194.
Christ-Crain M, Morgenthaler NG, Fenske W (2016) Copeptin as a
biomarker and a diagnostic tool in the evaluation of patients with
polyuria-polydipsia and hyponatremia. Best Pract Res Clin Endocrinol
Metab 30(2):235-47.
Christ-Crain M, Refardt J, Winzeler B (2022) Approach to the Patient:
Utility of the Copeptin Assay. J Clin Endocrinol Metab
(6):1727–1738.
Devi S, Jani RG, Karlette Anne F, Singh RD (2009) Study on Clinical
symptoms in canine cardiac diseases. Veterinary World 2 (8):307-
Dieplinger B, Gegenhuber A, Haltmayer M, Mueller T (2009) Evaluation
of novel biomarkers for the diagnosis of acute destabilised heart
failure in patients with shortness of breath. Heart 95 (18):1508-1513.
Gegenhuber A, Struck J, Dieplinger B, Poelz W, Pacher R, Morgenthaler
NG, Bergmann A, Haltmayer M, Mueller T (2007) 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 13(1):42-49.
Häggström J, Kvart C, Hansson K (1995) Heart Sounds and Murmurs:
Changes Related to Severity of Chronic Valvular Disease in the
Cavalier King Charles Spaniel. J Vet Intern Med 9(2):75-85.
Häggström J, Hansson K, Kvart C, Pedersen HD, Vuolteenaho O, Olsson
K (2000) Relationship between different natriuretic peptides and
severity of naturally acquired mitral regurgitation in dogs with
chronic myxomatous valve disease. JVet Cardiol 2(1):7-16.
Hansson K, Häggström J, Kvart C, Lord P (2002) Left atrial to aortic
root indices using Two-Dimensional and M-Mode echocaridography
in Cavalier King Charles Spaniels withhout left atrial enlargement.
Vet Radiol Ultrasound 43 (6): 568-575.
Healey JS, Davies RF, Smith SJ, Smith SJ, Davies RA, Ooi DS (2003)
Prognostic use of cardiac troponin T and troponin I in patients with
heart failure. Can J Cardiol 19(4):383–386.
Holler PJ, Wess G (2014) Sphericity index and E‐point‐to‐septal‐separation
(EPSS) to diagnose dilated cardiomyopathy in Doberman
Pinschers.J Vet Intern Med 28(1):123-129.
Horwich TB, Fonarow GC, Hamilton MA, et al. (2002) Anemia isassociated
with worse symptoms, greater impairment in functional ca-pacity and a significant increase in mortality in patients with
advancedheart failure. J Am Coll Cardiol 39:1780–1786.
Jeong JH, Seo YH, Ahn JY, Kim KH, Seo JY, Chun KY, Lim YS, Park
PW (2020) Performance of Copeptin for Early Diagnosis of Acute
Myocardial Infarction in an Emergency Department Setting. Ann
Lab Med 40(1):7-14.
Jougasaki M, Grantham JA, Redfield MM, Burnett JC (2001)Regulation
of cardiac adrenomedullin in heart failure. Peptides 22(11):1841-50.
Keene BW, Atkins CE, Bonagura JD, Fox PR, Haggström J, Fuentes
VL, Oyama MA, Rush JE, Stepien R, Uechi M (2019) ACVIM
consensus guidelines for the diagnosis and treatment of myxomatous
mitral valve disease in dogs. J Vet Intern Med 33 (3):1127-1140.
Kelly D, Squire IB, Khan SQ, Quinn P, Struck J, Morgenthaler NG,
Davies JE, Ng LL (2008) C-terminal provasopressin (copeptin)
is associated with left ventricular dysfunction, remodeling, and
clinical heart failure in survivors of myocardial infarction. J Card
Fail 14(9):739-45.
Khan SQ, O’Brien RJ, Struck J, Quinn P, Morgenthaler N, Squire I,
Davies J, Bergmann A, Ng LL (2007) Prognostic value of midregional
pro-adrenomedullin in patients with acute myocardial infarction:
the LAMP (Leicester Acute Myocardial Infarction Peptide)
study. J Am CollCardiol 49(14):1525-1532.
Langhorn R, Willesen JL (2016) Cardiac troponins in dogs and cats. J
Vet Intern Med30(1):36-50.
Lenka Š, Špinarová M, Goldbergová MP, Špinar J, Pařenica J, Ludka O,
Lábr K, Melek F, Ostadal P, Vondrakova D, Tomandl J, Sevcikova
J, Lipkova J, Benesova K, Jarkovsky J (2018) Prognostic Impact
of Copeptin and Mid-Regional Pro-Adrenomedullin in Chronic
Heart Failure with Regard to Comorbidities. J Cardiovasc Dis Diagn
(4):1–5.
Lorubbio M, Conti AA, Ognibene A (2018) Midregional pro-adrenomedullin
(MR-ProADM) reference values in serum. Clin Biochem
:173–174.
Maisel A, Xue Y, Shah K, Mueller C, Nowak R, Peacock WF,Ponikowski
P, Mockel M, Hogan C, et all (2011) Increased 90-day mortality in
patients with acute heart failure with elevated copeptin: secondary
results from the Biomarkers in Acute Heart Failure (BACH) study.
Circ Heart Fail4(5):613-620.
Morgenthaler NG, Struck J, Alonso C, Bergmann A (2005) Measurement
of midregional proadrenomedullin in plasma with an immunoluminometric
assay. Clin Chem 51 (10):1823-1829.
Nakamura M, Yoshida H, Makita S, Arakawa N, Niinuma H, Hiramori K
(1997) Potent and long-lasting vasodilatory effects of adrenomedullin
in humans: comparisons between normal subjects and patients
with chronic heart failure. Circulation 95(5):1214-1221.
Nakamura K, Kawamoto S, Osuga T, Morita T, Sasaki N, Morishita K,
Ohta H, Takiguchi M (2017) Left Atrial Strain at Different Stages
of Myxomatous Mitral Valve Disease in Dogs. J Vet Intern Med
(2):316–325.
Neuhold S, Huelsmann M, Strunk G, Stoiser B, Struck J, Morgenthaler
NG, Bergmann A, et all (2008) Comparison of copeptin, B-type
natriuretic peptide, and amino-terminal pro-B-type natriuretic peptide
in patients with chronic heart failure: prediction of death at
different stages of the disease.J Am Coll Cardiol 52 (4):266-272.
Nicholls MG, Charles CJ, Lainchbury JG, Lewis LK, Rademaker MT,
Richards AM, Yandle TG (2003) Adrenomedullin in heart failure.
Hypertens Res 26:135–140.
Nicholls MG (2004) Hemodynamic and hormonal actions of adrenomedullin.
BJMBR 37 (8):1247-1253.
Nigro N, Müller B, Morgenthaler NG, Fluri F, Schütz P, Neidert S,
Stolz D, et all (2011) The use of copeptin, the stable peptide of the
vasopressin precursor, in the differential diagnosis of sodium imbalance
in patients with acute diseases. Swiss Med Wkly 141:w13270.
Nishikimi T, Saito Y, Kitamura K, Ishimitsu T, Eto T, Kangawa K,
Matsuoka H, Nishikimi T (1995) Increased plasma levels of
adrenomedullin in patients with heart failure. J Am Coll Cardiol
(6):1424-1431.
Noszczyk-Nowak A (2011) NT-pro-BNP and troponin I as predictors of
morality in dogs with hearth failure. Pol J Vet Sci 14(4):551-556.
Omland T, De Lemos JA, Sabatine MS, Christophi CA, Rice MM,
Jablonski KA, Tjora S, Domanski MJ, Gersh BJ, Rouleau JL, Pfeffer
MA, Braunwald E (2009) A sensitive cardiac troponin T assay in
stable coronary artery disease. N Engl J Med 361 (26): 2538-2547.
Oyama MA, Sisson DD (2004) Cardiac troponin‐I concentration in dogs
with cardiac disease. J Vet Intern Med 18(6):831-839.
Oyama MA, Sisson DD, Bulmer BJ, Constable PD (2004) Echocardiographic
estimation of mean left atrial pressure in a canine model of
acute mitral valve insufficiency. J Vet Intern Med. 18(5):667–672.
Oyama MA, Fox PR, Rush JE, Rozanski EA, Lesser M (2008) Clinical
utility of serum N-terminal pro-B-type natriuretic peptide concentration
for identifying cardiac disease in dogs and assessing disease
severity. J Am Vet Med Assoc 232(10):1496-1503.
Peacock WF, Nowak R, Christenson R, DiSomma S, Neath SX, Hartmann
O, Mueller C, Ponikowski P, Möckel M, Hogan C, et all
(2011) Short-term mortality risk in emergency department acute
heart failure. Acad Emerg Med 18(9):947-958.
Peacock WF (2014) Novel biomarkers in acute heart failure:
MR-pro-adrenomedullin. Clin Chem Lab Med52(10):1433-1435.
Pousset F, Masson F, Chavirovskaia O, Isnard R, Carayon A, Golmard
JL, Komajda M, et all (2000) Plasma adrenomedullin, a new independent
predictor of prognosis in patients with chronic heart failure.
Eur Heart J 21(12):1009-1014.
Prosek R, Sisson DD, Oyama MA, Solter PF (2007) Distinguishing
cardiac and noncardiac dyspnea in 48 dogs using plasma atrial
natriuretic factor, B-type natriuretic factor, endothelin, and cardiac
troponin-I. J Vet Intern Med 21(2):238-242.
Rademaker MT, Cameron VA, Charles CJ, Lainchbury JG, Nicholls
MG, Richards AM (2003) Adrenomedullin and heart failure. Regul
Pept 112(1):51-60.
Riegger AJ (1988) Role of vasopressin in experimental heart failure.
Eur Heart J 9 (suppl|_H):7-10.
Ruaux C, Scollan K, Suchodolski JS, Steiner JM, Sisson DD (2015)
Biologic variability in NT-proBNP and cardiac troponin-I in healthy
dogs and dogs with mitral valve degeneration. Vet Clin Pathol
(3):420–430.
Sola E, Annarein JC, Kerbert H, Verspaget W, Moreira R, Pose E, Ruiz
P, Cela R, Ruiz MR, López E, Graupera I, et all (2016) Plasma
copeptin as biomarker of disease progression and prognosis in cirrhosis.
J Hepatol 65(5):914-920.
Stoiser B, Mörtl D, Hulsmann M, Berger R, Struck J, Morgenthaler
NG, Bergmann A, Pacher R(2006) Copeptin, a fragment of the
vasopressin precursor, as a novel predictor of outcome in heart
failure. Eur J Clin Invest36(11):771-778.
Szinnai G, Morgenthaler NG, Berneis K, Struck J, Müller B, Keller U,
Christ-Crain M (2007) Changes in plasma copeptin, the C-terminal
portion of arginine vasopressin during water deprivation and excess
in healthy subjects. J Clin Endocrinol Metab92:3973-3978.
Takemura N, Toda N, Miyagawa Y, Asano K, Tejima K, Kanno N, Hirose
H (2009) Evaluation of plasma N-terminal pro-brain natriuretic
peptide (NT-proBNP) concentrations in dogs with mitral valve insufficiency.
JVet Med Sci 71(7):925-929.
Teichholz LE, Kreulen T, Herman MV, et al. (1976) Problems in echocardiographic
volume determinations: Echocardiographicangiographic
correlations in the presence or absence of asynergy. Am J
Cardiol 37 (1):7–11.
Tentzeris I, Jarai R, Farhan S, Perkmann T, Schwarz MA, Jakl G, Wojta
J, Huber K (2011) Complementary role of copeptin and high-sensitivity
troponin in predicting outcome in patients with stable chronic
heart failure. Eur J Heart Fail 13(7):726–733.
Thomas WP, Gaber CE, Jacobs GJ, Kaplan PM, Lombard CW, Vet M,
Moses BL (1993) Recommendations for standards in transthoracic
two‐dimensional echocardiography in the dog and cat. J Vet Intern
Med 7(4):247-252.
Xue Y, Taub P, Iqbal N, Fard A, Clopton P, Maisel A (2013) Mid-Region
pro-Adrenomedullin Adds Predictive Value to Clinical Predictors
and Framingham Risk Score for Long-Term Mortality in Stable
Outpatients with Heart Failure.Eur J Heart Fail15 (12):1343–1349.
Yancy CW, Jessup M, Bozkurt B, et al. (2013) ACCF/AHA guideline
for the management of heart failure: a report of the American College
of Cardiology Foundation/American Heart Association Task
Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147–239.
Zhong Y, Wang R, Yan L, Lin M, Liu X, You T (2017) Copeptin in
heart failure: review and meta-analysis. Clin Chim Acta 475:36-43.
