Background: Bioactive adrenomedullin 1-52 (bio-ADM) is a dynamic blood biomarker for real-time assessment of endothelial function. Bio-ADM was recently shown to be a prognostic marker in patients with acute heart failure and cardiogenic shock. The aim of this study was to assess the predictive capacity of bio-ADM for cardiovascular outcome in stable patients with high cardiovascular risk. 

Methods: Circulating bio-ADM levels were assessed in n=695 stable patients with high cardiovascular risk hospitalized at the Department of Cardiology at University Hospital Aachen, Germany (all-comer cohort). Endpoints evaluated were all-cause mortality and cardiovascular mortality; follow up was 3 years. 

Results: Bio-ADM was higher in non-survivors (all-cause death: n=54, median 33.1 pg/mL; cardiovascular death: n=22, median 42.2 pg/mL) compared to survivors (n=641, median 17.9 pg/mL, p<0.0001). Univariable Cox regression analyses found bio-ADM to be associated with adverse outcome [standardized hazard ratio (HR) of bio-ADM values: All-cause death: 2.4, 95% confidence interval (CI): 2.0-2.9; c index 0.80; p<0.0001, cardiovascular death: 2.5, 95% confidence interval (CI): 1.9-3.3; c index 0.86, p<0.0001]. Time-dependent receiver operating characteristic curve analyses illustrated that bio-ADM is a strong biomarker for all-cause (AUC: 0.80, Chi²: 54.1) and cardiovascular (AUC: 0.86, Chi2: 28.9) mortality and proved to be superior to other markers including hs-CRP (AUC: 0.69, Chi²: 12.4), hs-Troponin T (AUC: 0.61, Chi²: 2.0), HbA1c (AUC: 0.65, Chi²: 13.8) and creatinine (AUC: 0.63, Chi²: 19.2). For both endpoints, bio-ADM provided added predictive value on top of each of the above markers (all p<0.0002 for all-cause mortality and p<0.010 for cardiovascular mortality).

Conclusion: Bio-ADM is strong biomarker for all-cause and cardiovascular death and proved to be superior to other established risk markers in stable patients with high cardiovascular risk.