Biomarker-enhanced cardiovascular risk prediction in patients with cancer: a prospective cohort study.

C-reactive protein N-terminal pro-BNP cardio-oncology cardiovascular biomarkers growth differentiation factor 15 inflammation lipoprotein(a) major adverse cardiovascular events personalized risk assessment precision medicine prevention

Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
29 Aug 2024
Historique:
received: 06 05 2024
revised: 23 07 2024
accepted: 29 07 2024
medline: 3 9 2024
pubmed: 3 9 2024
entrez: 2 9 2024
Statut: aheadofprint

Résumé

Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but tailored tools for cardiovascular risk prediction remain unavailable. To assess a broad panel of cardiovascular biomarkers and risk factors for the prediction of MACE and cardiovascular death in cancer patients. In total, 2192 patients with newly diagnosed or recurrent cancer were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death. Univariable and multivariable risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with adverse outcomes, and a risk score was developed. Traditional cardiovascular risk factors and selected cancer types were linked to higher MACE risk. While levels of Lp(a), CRP, and GDF-15 did not associate with MACE, levels of ICAM-1, P-/E-/L-selectins, and NT-proBNP were independently linked to 2-year MACE risk. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age of ≥60 years and +2 points for atherosclerotic disease, yielding a bootstrapped C-statistic of 0.76 (95% CI: 0.71-0.81) for the prediction of 2-year MACE. Implementation of biomarker data conferred improved performance (0.83, 95% CI: 0.78-0.88), with a simplified model showing similar performance (0.80, 95% CI: 0.74-0.86). The biomarker-enhanced and simplified prediction models achieved a C-statistic of 0.82 (95% CI: 0.71-0.93) and 0.74 (95% CI: 0.64-0.83) for the prediction of 5-year cardiovascular death. Biomarker-enhanced risk prediction strategies allow the identification of cancer patients at high risk of MACE and cardiovascular death. While external validation studies are ongoing, this first-of-its-kind risk score may provide the basis for personalized cardiovascular risk assessment across cancer entities.

Sections du résumé

BACKGROUND BACKGROUND
Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but tailored tools for cardiovascular risk prediction remain unavailable.
OBJECTIVES OBJECTIVE
To assess a broad panel of cardiovascular biomarkers and risk factors for the prediction of MACE and cardiovascular death in cancer patients.
METHODS METHODS
In total, 2192 patients with newly diagnosed or recurrent cancer were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death. Univariable and multivariable risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with adverse outcomes, and a risk score was developed.
RESULTS RESULTS
Traditional cardiovascular risk factors and selected cancer types were linked to higher MACE risk. While levels of Lp(a), CRP, and GDF-15 did not associate with MACE, levels of ICAM-1, P-/E-/L-selectins, and NT-proBNP were independently linked to 2-year MACE risk. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age of ≥60 years and +2 points for atherosclerotic disease, yielding a bootstrapped C-statistic of 0.76 (95% CI: 0.71-0.81) for the prediction of 2-year MACE. Implementation of biomarker data conferred improved performance (0.83, 95% CI: 0.78-0.88), with a simplified model showing similar performance (0.80, 95% CI: 0.74-0.86). The biomarker-enhanced and simplified prediction models achieved a C-statistic of 0.82 (95% CI: 0.71-0.93) and 0.74 (95% CI: 0.64-0.83) for the prediction of 5-year cardiovascular death.
CONCLUSION CONCLUSIONS
Biomarker-enhanced risk prediction strategies allow the identification of cancer patients at high risk of MACE and cardiovascular death. While external validation studies are ongoing, this first-of-its-kind risk score may provide the basis for personalized cardiovascular risk assessment across cancer entities.

Identifiants

DOI: 10.1016/j.jtha.2024.07.019 PMID: 39223063
pubmed: 39223063
pii: S1538-7836(24)00436-7
doi: 10.1016/j.jtha.2024.07.019
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interests S.K. has received funding from the Jubiläumsstiftung SwissLife, the Lindenhof Foundation, the Novartis Foundation for Medical-Biological Research, the Swiss Heart Foundation, the Swiss Society of Cardiology, and the Theodor-Ida-Herzog-Egli Foundation, and materials and equipment from Roche Diagnostics. He has received travel support from the European Atherosclerosis Society, the European Society of Cardiology, the European Society of Clinical Investigation, Sphingotec GmbH, the 4TEEN4 Pharmaceuticals GmbH, and the PAM Theragnostics GmbH. L.L. is a co-inventor on the international patent WO/2020/226993 filed in April 2020. The patent relates to the use of antibodies that specifically bind IL-1α to reduce various sequelae of ischemia–reperfusion injury to the central nervous system. He further reports speaker fees from Daiichi Sankyo outside the submitted work. Moreover, he is counselor of the European Society for Clinical Investigation and has received fundings from the Novartis Foundation for Medical-Biological Research, the Swiss Heart Foundation, and the Italian Ministry of Health. T.M.S. declares funding from the Lindenhof Foundation. F.A.W. is supported by a grant of the Lindenhof Foundation (through S.K., T.F.L, and T.M.S.) and the Foundation for Cardiovascular Research—Zurich Heart House. He has received funding from the Fonds zur Förderung des akademischen Nachwuchses of the University of Zurich, the European Society of Cardiology, 4TEEN4 Pharmaceuticals GmbH, PAM Theragnostics GmbH, and Sphingotec GmbH outside the submitted work. Outside this work, I.P. reports honoraria for lectures from Bayer, BMS/Pfizer, and Sanofi and participation in advisory boards from Bayer and BMS/Pfizer. Outside this work, T.F.L. declares research and educational grants to the institution from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Menarini Foundation, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, and Vifor and honoraria from Amgen, Dacadoo, Daiichi Sankyo, Menarini Foundation, Novartis, Novo Nordisk, Philips, and Pfizer. He holds leadership positions at the European Society of Cardiology, Swiss Heart Foundation, and the Foundation for Cardiovascular Research—Zurich Heart House. C.A. reports honoraria for lectures from Bayer, Daiichi Sankyo, BMS/Pfizer, and Sanofi and participation in advisory boards from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and BMS/Pfizer. F.Moik reports honoraria for lectures from BMS and MSD and participation in advisory boards from BMS. All other authors have no competing interests to disclose.

Auteurs

Simon Kraler (S)

Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Department of Internal Medicine, Cantonal Hospital Baden, Baden, Switzerland. Electronic address: https://twitter.com/KralerSimon.

Luca Liberale (L)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy. Electronic address: https://twitter.com/liberale_luca.

Stephan Nopp (S)

Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.

Cornelia Englisch (C)

Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.

Ella Grilz (E)

Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.

Tetiana Lapikova-Bryhinska (T)

Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland.

Alexander Akhmedov (A)

Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland.

Federico Carbone (F)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy. Electronic address: https://twitter.com/CarboneF82.

Davide Ramoni (D)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Amedeo Tirandi (A)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Alessandro Scuricini (A)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Simone Isoppo (S)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Curzia Tortorella (C)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Federica La Rosa (F)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Cristina Michelauz (C)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Federica Frè (F)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Aurora Gavoci (A)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Anna Lisa (A)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.

Thomas M Suter (TM)

Lindenhofgruppe, Bern and Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland.

Arnold von Eckardstein (A)

Institute of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland.

Florian A Wenzl (FA)

Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland. Electronic address: https://twitter.com/wenzl_florian.

Ingrid Pabinger (I)

Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.

Thomas F Lüscher (TF)

Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland; Royal Brompton and Harefield Hospitals and Imperial College, London, United Kingdom; School of Cardiovascular Medicine and Sciences, Kings College London, London, United Kingdom. Electronic address: https://twitter.com/TomLuscher.

Fabrizio Montecucco (F)

First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy.

Cihan Ay (C)

Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. Electronic address: cihan.ay@meduniwien.ac.at.

Florian Moik (F)

Department of Medicine I, Clinical Division of Haematology and Haemostaseology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria. Electronic address: https://twitter.com/FlorianMoik.

Classifications MeSH