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

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 C.

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

UR - https://www.scopus.com/pages/publications/85062720046

U2 - 10.1002/ejhf.1437

DO - 10.1002/ejhf.1437

M3 - Article

C2 - 30843353

SN - 1388-9842

VL - 21

SP - 732

EP - 743

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 6

ER -