Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure

Jozine M. ter Maaten, Daan Kremer, Biniyam Demissei, Joachim Struck, Andreas Bergmann, Stefan D. Anker, Leong Loke Ng, Kenneth Dickstein, Marco Metra, Nilesh J. Samani, Simon P. R. Romaine, John G. F. Cleland, Nicolas Girerd, Chim Lang, Dirk Jan van Veldhuisen, Adriaan A. Voors (Lead / Corresponding author)

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Abstract

Background: Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF. Methods and results: The association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r 2 = 0.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06–1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings. Conclusions: Plasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy.

Original languageEnglish
Pages (from-to)732-743
Number of pages12
JournalEuropean Journal of Heart Failure
Volume21
Issue number6
Early online date6 Mar 2019
DOIs
Publication statusPublished - 20 Jun 2019

Fingerprint

Adrenomedullin
Heart Failure
Edema
Venous Pressure
Hepatomegaly
Neck
Biomarkers
Angiotensin Receptor Antagonists
Respiratory Sounds
Angiotensin-Converting Enzyme Inhibitors
Signs and Symptoms
Blood Vessels
Cluster Analysis
Hospitalization
Body Mass Index

Keywords

  • Adrenomedullin
  • Bio-adrenomedullin
  • Congestion
  • Heart failure
  • Pro-adrenomedullin

Cite this

ter Maaten, J. M., Kremer, D., Demissei, B., Struck, J., Bergmann, A., Anker, S. D., ... Voors, A. A. (2019). Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure. European Journal of Heart Failure, 21(6), 732-743. https://doi.org/10.1002/ejhf.1437
ter Maaten, Jozine M. ; Kremer, Daan ; Demissei, Biniyam ; Struck, Joachim ; Bergmann, Andreas ; Anker, Stefan D. ; Ng, Leong Loke ; Dickstein, Kenneth ; Metra, Marco ; Samani, Nilesh J. ; Romaine, Simon P. R. ; Cleland, John G. F. ; Girerd, Nicolas ; Lang, Chim ; van Veldhuisen, Dirk Jan ; Voors, Adriaan A. / Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure. In: European Journal of Heart Failure. 2019 ; Vol. 21, No. 6. pp. 732-743.
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abstract = "Background: Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF. Methods and results: The association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r 2 = 0.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95{\%} confidence interval 1.06–1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings. Conclusions: Plasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy.",
keywords = "Adrenomedullin, Bio-adrenomedullin, Congestion, Heart failure, Pro-adrenomedullin",
author = "{ter Maaten}, {Jozine M.} and Daan Kremer and Biniyam Demissei and Joachim Struck and Andreas Bergmann and Anker, {Stefan D.} and Ng, {Leong Loke} and Kenneth Dickstein and Marco Metra and Samani, {Nilesh J.} and Romaine, {Simon P. R.} and Cleland, {John G. F.} and Nicolas Girerd and Chim Lang and {van Veldhuisen}, {Dirk Jan} and Voors, {Adriaan A.}",
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ter Maaten, JM, Kremer, D, Demissei, B, Struck, J, Bergmann, A, Anker, SD, Ng, LL, Dickstein, K, Metra, M, Samani, NJ, Romaine, SPR, Cleland, JGF, Girerd, N, Lang, C, van Veldhuisen, DJ & Voors, AA 2019, 'Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure', European Journal of Heart Failure, vol. 21, no. 6, pp. 732-743. https://doi.org/10.1002/ejhf.1437

Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure. / ter Maaten, Jozine M.; Kremer, Daan; Demissei, Biniyam; Struck, Joachim; Bergmann, Andreas; Anker, Stefan D.; Ng, Leong Loke; Dickstein, Kenneth; Metra, Marco; Samani, Nilesh J.; Romaine, Simon P. R.; Cleland, John G. F.; Girerd, Nicolas; Lang, Chim; van Veldhuisen, Dirk Jan; Voors, Adriaan A. (Lead / Corresponding author).

In: European Journal of Heart Failure, Vol. 21, No. 6, 20.06.2019, p. 732-743.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure

AU - ter Maaten, Jozine M.

AU - Kremer, Daan

AU - Demissei, Biniyam

AU - Struck, Joachim

AU - Bergmann, Andreas

AU - Anker, Stefan D.

AU - Ng, Leong Loke

AU - Dickstein, Kenneth

AU - Metra, Marco

AU - Samani, Nilesh J.

AU - Romaine, Simon P. R.

AU - Cleland, John G. F.

AU - Girerd, Nicolas

AU - Lang, Chim

AU - van Veldhuisen, Dirk Jan

AU - Voors, Adriaan A.

N1 - This project was funded by a grant from the European Commission: FP7-242209-BIOSTAT-CHF.

PY - 2019/6/20

Y1 - 2019/6/20

N2 - Background: Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF. Methods and results: The association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r 2 = 0.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06–1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings. Conclusions: Plasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy.

AB - Background: Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF. Methods and results: The association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r 2 = 0.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06–1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings. Conclusions: Plasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy.

KW - Adrenomedullin

KW - Bio-adrenomedullin

KW - Congestion

KW - Heart failure

KW - Pro-adrenomedullin

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U2 - 10.1002/ejhf.1437

DO - 10.1002/ejhf.1437

M3 - Article

VL - 21

SP - 732

EP - 743

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

SN - 1388-9842

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ER -