Adrenomedullin system dysregulation predicts cardiogenic shock and mortality in acute coronary syndromes
Yifan WangNicolas DanchinTabassome SimonMarianne ZellerYulia IlinaPaul KaufmannAndreas BergmannFlorian A WenzlVictor SchweigerLuca LiberaleLorenz RäberChristian TemplinArnold von EckardsteinMarco RoffiOlivier MüllerJeronim BerishaGiovanni G. CamiciLaurence BérardBirte ArltDavid NiederseerT F LuescherSimon Kraler
Key result
Higher ADM-Gly linked to ~44% greater in-hospital cardiogenic shock risk per log2 increase in stable ACS.
- aOR 1.44
- 95% CI 1.22-1.71
- P<.001
- n=4,922
Why the study?
Cardiogenic shock is a severe complication of acute coronary syndromes driven by endothelial dysfunction and vascular leakage, but biomarkers reflecting these early processes are lacking.
Do adrenomedullin system components predict in-hospital cardiogenic shock and 1-year mortality in initially stable patients with acute coronary syndromes?
Key Points
- To determine whether adrenomedullin system biomarkers (ADM-Gly, PAM, and bio-ADM) predict in-hospital cardiogenic shock and 1-year mortality in patients presenting with acute coronary syndromes without initial shock.
- Measured plasma ADM-Gly, PAM, and bio-ADM in two cohorts of acute coronary syndrome patients presenting without cardiogenic shock: SPUM-ACS (Switzerland, N=4,098) and FAST-MI (France, N=824).
- Evaluated associations with in-hospital cardiogenic shock and 1-year mortality using multivariable-adjusted regression models and tested incremental predictive value over the ORBI risk score.
- Adding ADM-Gly and bio-ADM to the ORBI risk score significantly improved discrimination (ΔAUC 0.02), risk reclassification (net reclassification improvement 0.229), and overall model fit (ΔAIC -26.9).
Study Design
Type
Cohort (n=4,922)
Multicenter
Yes
Structured PICO
Do adrenomedullin system components predict in-hospital cardiogenic shock and 1-year mortality in initially stable patients with acute coronary syndromes?
P
Population
4,922 patients with acute coronary syndromes without cardiogenic shock on admission, evaluated for in-hospital cardiogenic shock and 1-year mortality.
E
Exposure
Assessment of adrenomedullin (ADM) system components (ADM-Gly, PAM, and bio-ADM)
O
Outcome
In-hospital cardiogenic shock (CS)hard clinical
Main Result
Odds Ratio: 1.44 (95% CI 1.22–1.71)
p-value: p=<.001
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
DMDr. Martin Steen Frydland
“In this issue of the European Heart Journal, Wang and colleagues report a retrospective analysis of plasma concentrations of bioactive adrenomedullin (bio-ADM), its inactive precursor glycine-extended ADM (ADM-gly), and the activating enzyme peptidyl-glycine α-amidating monooxygenase (PAM) in patients with ACS. Biomarker levels were measured before percutaneous coronary intervention (PCI), and their associations with subsequent in-hospital CS and 1-year mortality were evaluated.”
“The study populations were similar with 52%/48% and 53%/47% STEMI/NSTE-ACS patients, respectively. Patients presenting with fulminant CS at hospital admission were excluded. During hospitalization, CS developed in 4.8% of patients in the SPUM-ACS cohort (198 of 4098 patients) and in 1.6% of the FAST-MI cohort (72 of 4579 patients in the subgroup with available blood samples).”
“While CS status was assessed clinically at admission, the timing of biomarker sampling relative to subsequent shock development was not reported, limiting interpretation of the biomarker plasma concentration and clinical deterioration.”
Implication
ADM-Gly and bio-ADM levels independently predict in-hospital cardiogenic shock and 1-year mortality in initially stable ACS patients, improving early risk stratification beyond established clinical scores.
Abstract
BACKGROUND AND AIMS: Cardiogenic shock (CS) is the most dreadful complication of acute coronary syndromes (ACS). Endothelial dysfunction and vascular leakage are hallmarks of CS pathophysiology; however, biomarkers reflecting these early processes are lacking. The adrenomedullin (ADM) system-the inactive precursor glycine-extended ADM (ADM-Gly), the activating enzyme peptidylglycine α-amidating monooxygenase (PAM), and biologically active ADM (bio-ADM)-modulates vascular tone and permeability. This study investigated associations of ADM system components with CS and 1-year mortality risk after ACS. METHODS: ADM-Gly, PAM, and bio-ADM were assessed in 4098 (Switzerland; SPUM-ACS) and 824 (France; FAST-MI) ACS patients without CS on admission. The primary endpoint was in-hospital CS; the secondary endpoint was 1-year mortality. Biomarker-outcome associations were analysed using multivariable-adjusted regression models, and the incremental predictive value beyond established risk scores was quantified. RESULTS: Higher ADM-Gly and bio-ADM, but not PAM, were associated with systemic inflammation and haemodynamic compromise. ADM-Gly and bio-ADM independently predicted CS risk in Switzerland (adjusted odds ratio [aOR] per log2 increase, 1.44, 95% confidence interval [CI] 1.22-1.71, P < .001 and aOR 1.37, 95% CI 1.10-1.70, P = .004) and France (adjusted risk ratio [RR] per log2 increase, 1.82, 95% CI 1.34-2.48, P < .001 and aRR 1.55, 95% CI 1.15-2.10, P = .004), and were associated with 1-year mortality risk (adjusted hazard ratio [aHR] per log2 increase, 1.33, 95% CI 1.09-1.61, P = .005 and aHR 1.46, 95% CI 1.15-1.86, P = .002). Addition of ADM-Gly and bio-ADM to the ORBI risk score improved its discrimination (Δ area under the receiver operating characteristic curve 0.02), reclassification (net reclassification improvement 0.229), and model fit (Δ Akaike information criterion -26.9), with consistent results in external validation. CONCLUSIONS: ADM-Gly and bio-ADM, but not PAM, independently predict in-hospital CS and 1-year mortality risk in initially stable patients with ACS and improve early risk stratification.
Discussion
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Cite This Study
Wang et al. (2026) conducted a cohort in Acute coronary syndromes (n=4,922). Adrenomedullin system components (ADM-Gly and bio-ADM) was evaluated on in-hospital cardiogenic shock (aOR 1.44, 95% CI 1.22-1.71, p=<.001). Higher levels of ADM-Gly independently predicted in-hospital cardiogenic shock risk in initially stable ACS patients (aOR per log2 increase 1.44; 95% CI 1.22-1.71; P<0.001).