NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients

Rossignol, P. et al. (2022) NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients. European Heart Journal Open, 2(6), oeac069. (doi: 10.1093/ehjopen/oeac069) (PMID:36600882) (PMCID:PMC9797490)

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Abstract

Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine. Methods and results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD. Rosuvastatin vs. placebo had no significant effect on the composite primary endpoint of death from CV causes, nonfatal myocardial infarction or nonfatal stroke. We first compared CV risk-matched cases and controls (n = 410) to identify novel biomarkers using a multiplex proximity extension immunoassay (276 proteomic biomarkers assessed with OlinkTM). We replicated our findings in 200 unmatched cases and 200 controls. External validation was conducted from a multicentre real-life Danish cohort [Aarhus-Aalborg (AA), n = 331 patients] in which 92 OlinkTM biomarkers were assessed. In AURORA, only N-terminal pro-brain natriuretic peptide (NT-proBNP, positive association) and stem cell factor (SCF) (negative association) were found consistently associated with the trial's primary outcome across exploration and replication phases, independently from the baseline characteristics. Stem cell factor displayed a lower added predictive ability compared with NT-ProBNP. In the AA cohort, in multivariable analyses, BNP was found significantly associated with major CV events, while higher SCF was associated with less frequent CV deaths. Conclusions: Our findings suggest that NT-proBNP and SCF may help identify ESRD patients with respectively high and low CV risk, beyond classical clinical predictors and also point at novel pathways for prevention and treatment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jardine, Professor Alan
Authors: Rossignol, P., Duarte, K., Bresso, E., Åsberg, A., Devignes, M.D., Eriksson, N., Girerd, N., Glerup, R., Jardine, A.G., Holdaas, H., Lamiral, Z., Leroy, C., Massy, Z., März, W., Krämer, B., Wu, P.H., Schmieder, R., Soveri, I., Christensen, J.H., Svensson, M., Zannad, F., and Fellström, B.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:European Heart Journal Open
Publisher:Oxford University Press
ISSN:2752-4191
ISSN (Online):2752-4191
Published Online:09 November 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in European Heart Journal Open 2(6): oeac069
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190666HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507Institute of Cardiovascular & Medical Sciences