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

Berkan Kurt; Matthias Rau; Oliver Hartmann; Andreas Bergmann; Martin Reugels; Susanne Just; Florian A Wenzl; Julia Moellmann; Jens Spießhöfer; Andrea Milzi; Kinan Kneizeh; Kirsten Thiele; Mathias Hohl; Simina-Ramona Selejan; Emiel P C van der Vorst; Edgar Dahl; Jörg Schröder; Thomas F Lüscher; Nikolaus Marx; Michael Lehrke; Florian Kahles

doi:10.1016/j.atherosclerosis.2025.120220

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

Berkan Kurt
, Matthias Rau
, Oliver Hartmann
, Andreas Bergmann
, Martin Reugels
, Susanne Just
, Florian A Wenzl
, Julia Moellmann
, Jens Spießhöfer
, Andrea Milzi
, Kinan Kneizeh
, Kirsten Thiele
, Mathias Hohl
, Simina-Ramona Selejan
, Emiel P C van der Vorst
, Edgar Dahl
, Jörg Schröder
, Thomas F Lüscher
, Nikolaus Marx
, Michael Lehrke

Florian Kahles

Traunstein Hospital

RWTH Aachen University
SphingoTec GmbH
Wyss Zurich (University of Zurich)
Saarland University Hospital and Saarland University Faculty of Medicine
Klinikum Traunstein

Research output: Contribution to journal › Original Article › peer-review

Abstract

BACKGROUND AND AIMS: Bioactive adrenomedullin 1-52 (bio-ADM) is a novel biomarker for the assessment of endothelial function and prediction of adverse outcomes in patients with acute heart failure and cardiogenic shock. The SMART (Second Manifestations of Arterial Disease) risk score is a validated tool for risk assessment in patients with established atherosclerotic cardiovascular disease (ASCVD). Here we assessed whether bio-ADM adds incremental prognostic value to the SMART risk score in stable patients with ASCVD.

METHODS: Circulating bio-ADM levels were measured in 452 stable patients with ASCVD. Endpoints evaluated were all-cause and cardiovascular mortality; follow up was 3 years.

RESULTS: Bio-ADM was higher in non-survivors (n = 45; median 36.8 pg/mL) compared to survivors (n = 407; median 18.3 pg/mL; p < 0.0001). Bio-ADM was found to be a strong predictor for all-cause mortality (Chi2: 44.58; C-index: 0.79) as well as cardiovascular death (Chi2: 33.29; C-index: 0.85) and proved to be superior to other markers including hs-Troponin T (Chi2: 7.77; C-index: 0.73) and eGFRCKD-EPI 2021 (Chi2: 25.10; C-index: 0.70). In multivariable analyses adjusting for age, sex, diabetes mellitus, hypertension, smoking, NT-proBNP, and eGFRCKD-EPI 2021, bio-ADM remained independently associated with all-cause mortality (HR: 1.6; 95 % CI: 1.2-2.1; Chi2: 96.17; p < 0.00001; C-index: 0.89) and cardiovascular death (HR: 1.7; 95 % CI: 1.1-2.5; Chi2: 57.71; p < 0.00001; C-index: 0.88). Addition of bio-ADM to the SMART risk score meaningfully improved model performance in predicting mortality (SMART risk score: Chi2: 19.91; p = 0.0001; C-index: 0.69; SMART risk score + bio-ADM: Chi2: 54.51; p < 0.00001; C-index: 0.81).

CONCLUSIONS: Bio-ADM levels are independently associated with mortality and provide incremental added value on top of the SMART risk score in stable patients with ASCVD.

Original language	English
Pages (from-to)	120220
Journal	ATHEROSCLEROSIS
Volume	406
DOIs	https://doi.org/10.1016/j.atherosclerosis.2025.120220
Publication status	Published - Jul 2025

Keywords

Humans
Adrenomedullin/blood
Male
Female
Aged
Middle Aged
Risk Assessment
Biomarkers/blood
Prognosis
Predictive Value of Tests
Atherosclerosis/blood
Risk Factors
Time Factors
Cause of Death
Decision Support Techniques

Access to Document

10.1016/j.atherosclerosis.2025.120220

Cite this

Kurt, B., Rau, M., Hartmann, O., Bergmann, A., Reugels, M., Just, S., Wenzl, F. A., Moellmann, J., Spießhöfer, J., Milzi, A., Kneizeh, K., Thiele, K., Hohl, M., Selejan, S.-R., van der Vorst, E. P. C., Dahl, E., Schröder, J., Lüscher, T. F., Marx, N., ... Kahles, F. (2025). Adjustment of the SMART risk score by bioactive adrenomedullin enables a more accurate prediction of mortality in patients with ASCVD. ATHEROSCLEROSIS , 406, 120220. https://doi.org/10.1016/j.atherosclerosis.2025.120220

Kurt, Berkan ; Rau, Matthias ; Hartmann, Oliver et al. / Adjustment of the SMART risk score by bioactive adrenomedullin enables a more accurate prediction of mortality in patients with ASCVD. In: ATHEROSCLEROSIS 2025 ; Vol. 406. pp. 120220.

@article{58a11747e8c1448db3cdbf557e452b2b,

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

abstract = "BACKGROUND AND AIMS: Bioactive adrenomedullin 1-52 (bio-ADM) is a novel biomarker for the assessment of endothelial function and prediction of adverse outcomes in patients with acute heart failure and cardiogenic shock. The SMART (Second Manifestations of Arterial Disease) risk score is a validated tool for risk assessment in patients with established atherosclerotic cardiovascular disease (ASCVD). Here we assessed whether bio-ADM adds incremental prognostic value to the SMART risk score in stable patients with ASCVD.METHODS: Circulating bio-ADM levels were measured in 452 stable patients with ASCVD. Endpoints evaluated were all-cause and cardiovascular mortality; follow up was 3 years.RESULTS: Bio-ADM was higher in non-survivors (n = 45; median 36.8 pg/mL) compared to survivors (n = 407; median 18.3 pg/mL; p < 0.0001). Bio-ADM was found to be a strong predictor for all-cause mortality (Chi2: 44.58; C-index: 0.79) as well as cardiovascular death (Chi2: 33.29; C-index: 0.85) and proved to be superior to other markers including hs-Troponin T (Chi2: 7.77; C-index: 0.73) and eGFRCKD-EPI 2021 (Chi2: 25.10; C-index: 0.70). In multivariable analyses adjusting for age, sex, diabetes mellitus, hypertension, smoking, NT-proBNP, and eGFRCKD-EPI 2021, bio-ADM remained independently associated with all-cause mortality (HR: 1.6; 95 \% CI: 1.2-2.1; Chi2: 96.17; p < 0.00001; C-index: 0.89) and cardiovascular death (HR: 1.7; 95 \% CI: 1.1-2.5; Chi2: 57.71; p < 0.00001; C-index: 0.88). Addition of bio-ADM to the SMART risk score meaningfully improved model performance in predicting mortality (SMART risk score: Chi2: 19.91; p = 0.0001; C-index: 0.69; SMART risk score + bio-ADM: Chi2: 54.51; p < 0.00001; C-index: 0.81).CONCLUSIONS: Bio-ADM levels are independently associated with mortality and provide incremental added value on top of the SMART risk score in stable patients with ASCVD.",

keywords = "Humans, Adrenomedullin/blood, Male, Female, Aged, Middle Aged, Risk Assessment, Biomarkers/blood, Prognosis, Predictive Value of Tests, Atherosclerosis/blood, Risk Factors, Time Factors, Cause of Death, Decision Support Techniques",

author = "Berkan Kurt and Matthias Rau and Oliver Hartmann and Andreas Bergmann and Martin Reugels and Susanne Just and Wenzl, \{Florian A\} and Julia Moellmann and Jens Spie{\ss}h{\"o}fer and Andrea Milzi and Kinan Kneizeh and Kirsten Thiele and Mathias Hohl and Simina-Ramona Selejan and \{van der Vorst\}, \{Emiel P C\} and Edgar Dahl and J{\"o}rg Schr{\"o}der and L{\"u}scher, \{Thomas F\} and Nikolaus Marx and Michael Lehrke and Florian Kahles",

note = "nicht zu werten, keine Aff. zu Traunstein",

year = "2025",

month = jul,

doi = "10.1016/j.atherosclerosis.2025.120220",

language = "English",

volume = "406",

pages = "120220",

journal = "ATHEROSCLEROSIS ",

issn = "0021-9150",

publisher = "Elsevier ",

}

Kurt, B, Rau, M, Hartmann, O, Bergmann, A, Reugels, M, Just, S, Wenzl, FA, Moellmann, J, Spießhöfer, J, Milzi, A, Kneizeh, K, Thiele, K, Hohl, M, Selejan, S-R, van der Vorst, EPC, Dahl, E, Schröder, J, Lüscher, TF, Marx, N, Lehrke, M & Kahles, F 2025, 'Adjustment of the SMART risk score by bioactive adrenomedullin enables a more accurate prediction of mortality in patients with ASCVD', ATHEROSCLEROSIS , vol. 406, pp. 120220. https://doi.org/10.1016/j.atherosclerosis.2025.120220

Adjustment of the SMART risk score by bioactive adrenomedullin enables a more accurate prediction of mortality in patients with ASCVD. / Kurt, Berkan; Rau, Matthias; Hartmann, Oliver et al.
In: ATHEROSCLEROSIS , Vol. 406, 07.2025, p. 120220.

Research output: Contribution to journal › Original Article › peer-review

TY - JOUR

T1 - Adjustment of the SMART risk score by bioactive adrenomedullin enables a more accurate prediction of mortality in patients with ASCVD

AU - Kurt, Berkan

AU - Rau, Matthias

AU - Hartmann, Oliver

AU - Bergmann, Andreas

AU - Reugels, Martin

AU - Just, Susanne

AU - Wenzl, Florian A

AU - Moellmann, Julia

AU - Spießhöfer, Jens

AU - Milzi, Andrea

AU - Kneizeh, Kinan

AU - Thiele, Kirsten

AU - Hohl, Mathias

AU - Selejan, Simina-Ramona

AU - van der Vorst, Emiel P C

AU - Dahl, Edgar

AU - Schröder, Jörg

AU - Lüscher, Thomas F

AU - Marx, Nikolaus

AU - Lehrke, Michael

AU - Kahles, Florian

N1 - nicht zu werten, keine Aff. zu Traunstein

PY - 2025/7

Y1 - 2025/7

N2 - BACKGROUND AND AIMS: Bioactive adrenomedullin 1-52 (bio-ADM) is a novel biomarker for the assessment of endothelial function and prediction of adverse outcomes in patients with acute heart failure and cardiogenic shock. The SMART (Second Manifestations of Arterial Disease) risk score is a validated tool for risk assessment in patients with established atherosclerotic cardiovascular disease (ASCVD). Here we assessed whether bio-ADM adds incremental prognostic value to the SMART risk score in stable patients with ASCVD.METHODS: Circulating bio-ADM levels were measured in 452 stable patients with ASCVD. Endpoints evaluated were all-cause and cardiovascular mortality; follow up was 3 years.RESULTS: Bio-ADM was higher in non-survivors (n = 45; median 36.8 pg/mL) compared to survivors (n = 407; median 18.3 pg/mL; p < 0.0001). Bio-ADM was found to be a strong predictor for all-cause mortality (Chi2: 44.58; C-index: 0.79) as well as cardiovascular death (Chi2: 33.29; C-index: 0.85) and proved to be superior to other markers including hs-Troponin T (Chi2: 7.77; C-index: 0.73) and eGFRCKD-EPI 2021 (Chi2: 25.10; C-index: 0.70). In multivariable analyses adjusting for age, sex, diabetes mellitus, hypertension, smoking, NT-proBNP, and eGFRCKD-EPI 2021, bio-ADM remained independently associated with all-cause mortality (HR: 1.6; 95 % CI: 1.2-2.1; Chi2: 96.17; p < 0.00001; C-index: 0.89) and cardiovascular death (HR: 1.7; 95 % CI: 1.1-2.5; Chi2: 57.71; p < 0.00001; C-index: 0.88). Addition of bio-ADM to the SMART risk score meaningfully improved model performance in predicting mortality (SMART risk score: Chi2: 19.91; p = 0.0001; C-index: 0.69; SMART risk score + bio-ADM: Chi2: 54.51; p < 0.00001; C-index: 0.81).CONCLUSIONS: Bio-ADM levels are independently associated with mortality and provide incremental added value on top of the SMART risk score in stable patients with ASCVD.

AB - BACKGROUND AND AIMS: Bioactive adrenomedullin 1-52 (bio-ADM) is a novel biomarker for the assessment of endothelial function and prediction of adverse outcomes in patients with acute heart failure and cardiogenic shock. The SMART (Second Manifestations of Arterial Disease) risk score is a validated tool for risk assessment in patients with established atherosclerotic cardiovascular disease (ASCVD). Here we assessed whether bio-ADM adds incremental prognostic value to the SMART risk score in stable patients with ASCVD.METHODS: Circulating bio-ADM levels were measured in 452 stable patients with ASCVD. Endpoints evaluated were all-cause and cardiovascular mortality; follow up was 3 years.RESULTS: Bio-ADM was higher in non-survivors (n = 45; median 36.8 pg/mL) compared to survivors (n = 407; median 18.3 pg/mL; p < 0.0001). Bio-ADM was found to be a strong predictor for all-cause mortality (Chi2: 44.58; C-index: 0.79) as well as cardiovascular death (Chi2: 33.29; C-index: 0.85) and proved to be superior to other markers including hs-Troponin T (Chi2: 7.77; C-index: 0.73) and eGFRCKD-EPI 2021 (Chi2: 25.10; C-index: 0.70). In multivariable analyses adjusting for age, sex, diabetes mellitus, hypertension, smoking, NT-proBNP, and eGFRCKD-EPI 2021, bio-ADM remained independently associated with all-cause mortality (HR: 1.6; 95 % CI: 1.2-2.1; Chi2: 96.17; p < 0.00001; C-index: 0.89) and cardiovascular death (HR: 1.7; 95 % CI: 1.1-2.5; Chi2: 57.71; p < 0.00001; C-index: 0.88). Addition of bio-ADM to the SMART risk score meaningfully improved model performance in predicting mortality (SMART risk score: Chi2: 19.91; p = 0.0001; C-index: 0.69; SMART risk score + bio-ADM: Chi2: 54.51; p < 0.00001; C-index: 0.81).CONCLUSIONS: Bio-ADM levels are independently associated with mortality and provide incremental added value on top of the SMART risk score in stable patients with ASCVD.

KW - Humans

KW - Adrenomedullin/blood

KW - Male

KW - Female

KW - Aged

KW - Middle Aged

KW - Risk Assessment

KW - Biomarkers/blood

KW - Prognosis

KW - Predictive Value of Tests

KW - Atherosclerosis/blood

KW - Risk Factors

KW - Time Factors

KW - Cause of Death

KW - Decision Support Techniques

U2 - 10.1016/j.atherosclerosis.2025.120220

DO - 10.1016/j.atherosclerosis.2025.120220

M3 - Original Article

C2 - 40449381

SN - 0021-9150

VL - 406

SP - 120220

JO - ATHEROSCLEROSIS

JF - ATHEROSCLEROSIS

ER -

Kurt B, Rau M, Hartmann O, Bergmann A, Reugels M, Just S et al. Adjustment of the SMART risk score by bioactive adrenomedullin enables a more accurate prediction of mortality in patients with ASCVD. ATHEROSCLEROSIS . 2025 Jul;406:120220. doi: 10.1016/j.atherosclerosis.2025.120220

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

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Keywords

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