Adjustment of the SMART risk score by bioactive adrenomedullin enables a more accurate prediction of mortality in patients with ASCVD

Berkan Kurt (Aachen)1, M. Rau (Aachen)1, O. Hartmann (Hennigsdorf)2, F. Lobo de Sá (Hennigsdorf)2, J. Möllmann (Aachen)1, J. Spießhöfer (Aachen)3, J. Wipperfürth (Aachen)4, E. Dahl (Aachen)4, N. Marx (Aachen)1, M. Lehrke (Aachen)1, F. Kahles (Aachen)1

1Uniklinik RWTH Aachen Med. Klinik I - Kardiologie, Angiologie und Internistische Intensivmedizin Aachen, Deutschland; 2Sphingotec GmbH Hennigsdorf, Deutschland; 3Uniklinik RWTH Aachen Med. Klinik V - Klinik für Pneumologie und Internistische Intensivmedizin Aachen, Deutschland; 4Uniklinik RWTH Aachen RWTH cBMB at the Institute of Pathology Aachen, Deutschland


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 SMART (Second Manifestations of Arterial Disease) score is a validated tool for risk assessment in patients with established atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to assess whether measurement of bio-ADM adds incremental value to the SMART score in stable patients with ASCVD.


Methods: Circulating bio-ADM levels were assessed in n=695 stable patients with ASCVD 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) compared to survivors (n=641, median 17.9 pg/mL; p<0.0001). Univariable Cox regression analyses showed 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; p<0.001, cardiovascular death: 2.5, 95% CI: 1.9-3.3; p<0.001]. This association remained significant in various multivariable Cox regression models. Bio-ADM was found to be a strong marker for mortality (c-index: 0.80, Chi2: 54.1) and proved to be superior to other markers including hs-Troponin T (c-index: 0.61, Chi2: 2.0) and eGFR CKD-EPI 2021 (c-index: 0.687, Chi2: 33.5). Addition of bio-ADM to the SMART score significantly improved model performance in predicting mortality (SMART score: c-index: 0.717, Chi2: 24.73; SMART score + bio-ADM: c-index: 0.832, Chi2: 63.24; Delta c-index: 0.115; Delta Chi2: 38.51; all p<0.001).



Bio-ADM provides incremental added value (improved discrimination and calibration) on top of the SMART risk score in patients with ASCVD.

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