Identification of sex‐specific biomarkers predicting new‐onset heart failure

Raafs, A. et al. (2021) Identification of sex‐specific biomarkers predicting new‐onset heart failure. ESC Heart Failure, 8(5), pp. 3512-3520. (doi: 10.1002/ehf2.13476) (PMID:34156155) (PMCID:PMC8497379)

[img] Text
244600.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial.



Aims: Heart failure (HF) is common in both men and women, yet disease pathophysiology, presentation, and progression differ between sexes. Studies addressing whether biomarkers predict new onset HF sex-specifically are scarce. This study therefore aims to test the sex-specificity of 252 protein biomarkers for new-onset HF. Methods and results: A matched case–control design in patients selected from cohorts within the HOMAGE consortium was used. Cases (new-onset HF, n = 562) and controls (n = 780) were matched for cohort (PREDICTOR, HEALTH-ABC, & PROSPER), follow-up time (defined as time from entry to incident HF), and age. Incident HF was defined as first hospitalization for HF. Targeted plasma proteins (n = 252) were measured using Proximity Extension Assay technology from O-link. To look for sex differences for new onset HF, we adjusted for cohort, age, and baseline clinical parameters. At baseline, women had a biomarker profile reflecting activated metabolism and immune responses. However, none of the biomarkers had a significant interaction with sex in predicting new onset HF, but four biomarkers had a trend towards sex-specificity (P < 0.013). E-selectin and interleukin 1 receptor antagonist were more female-specific, whereas IL17A and CHIT1 tended to be male sex-specific for incident HF. Conclusions: The majority of biomarkers associated with incident HF did not significantly differ between women and men, despite clear differences in biomarkers at baseline.

Item Type:Articles
Additional Information:The research leading to these results has received funding from the European Union Commission's Seventh Framework Programme under grant agreement 305507 [HOMAGE (Heart Omics in Ageing consortium)]. We acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with the support of the Dutch Heart Foundation CVON2016-Early HFPEF, and CVON 2017-21, SHE-PREDICTS-HF. JPF, NG, PR, and FZ are supported by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d'Avenir” programme FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project “Lorraine Université d'Excellence”, reference ANR-15-IDEX-04-LUE. They thank the CRB lorrain for biobaking activities. JAS is supported by the Non-Profit Research Institute Alliance for the Promotion of Preventive Medicine (URL:, Mechelen, Belgium received a non-binding research grant from OMRON Healthcare Co., Ltd., Kyoto, Japan.
Glasgow Author(s) Enlighten ID:Delles, Professor Christian and Cleland, Professor John and Ferreira, Mr Joao Pedro
Authors: Raafs, A., Verdonschot, J., Ferreira, J. P., Wang, P., Collier, T., Henkens, M., Björkman, J., Boccanelli, A., Clark, A. L., Delles, C., Diez, J., González, A., Girerd, N., Jukema, J. W., Pinet, F., Rossignol, P., Thum, T., Vodovar, N., de Boer, R. A., van Empel, V., Staessen, J. A., Hazebroek, M., Cleland, J., Zannad, F., and Heymans, S.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:ESC Heart Failure
ISSN (Online):2055-5822
Published Online:22 June 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in ESC Heart Failure 8(5): 3512-3520
Publisher Policy:Reproduced under a Creative Commons Licence

University Staff: Request a correction | Enlighten Editors: Update this record