Sex differences in circulating proteins in heart failure with preserved ejection fraction

Stienen, Susan, Ferreira, João Pedro, Kobayashi, Masatake, Preud’homme, Gregoire, Dobre, Daniela, Machu, Jean-Loup, Duarte, Kevin, Bresso, Emmanuel, Devignes, Marie-Dominique, Andrés, Natalia López, Girerd, Nicolas, Aakhus, Svend, Ambrosio, Giuseppe, Rocca, Hans-Peter Brunner-La, Fontes-Carvalho, Ricardo, Fraser, Alan G., van Heerebeek, Loek, de Keulenaer, Gilles, Marino, Paolo, McDonald, Kenneth, Mebazaa, Alexandre, Papp, Zoltàn, Raddino, Riccardo, Tschöpe, Carsten, Paulus, Walter J., Zannad, Faiez and Rossignol, Patrick 2020. Sex differences in circulating proteins in heart failure with preserved ejection fraction. Biology of Sex Differences 11 , 47. 10.1186/s13293-020-00322-7

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Abstract

Background Many patients with heart failure with preserved ejection fraction (HFpEF) are women. Exploring mechanisms underlying the sex differences may improve our understanding of the pathophysiology of HFpEF. Studies focusing on sex differences in circulating proteins in HFpEF patients are scarce. Methods A total of 415 proteins were analyzed in 392 HFpEF patients included in The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study (MEDIA-DHF). Sex differences in these proteins were assessed using adjusted logistic regression analyses. The associations between candidate proteins and cardiovascular (CV) death or CV hospitalization (with sex interaction) were assessed using Cox regression models. Results We found 9 proteins to be differentially expressed between female and male patients. Women expressed more LPL and PLIN1, which are markers of lipid metabolism; more LHB, IGFBP3, and IL1RL2 as markers of transcriptional regulation; and more Ep-CAM as marker of hemostasis. Women expressed less MMP-3, which is a marker associated with extracellular matrix organization; less NRP1, which is associated with developmental processes; and less ACE2, which is related to metabolism. Sex was not associated with the study outcomes (adj. HR 1.48, 95% CI 0.83–2.63), p = 0.18. Conclusion In chronic HFpEF, assessing sex differences in a wide range of circulating proteins led to the identification of 9 proteins that were differentially expressed between female and male patients. These findings may help further investigations into potential pathophysiological processes contributing to HFpEF.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	BioMed Central
ISSN:	2042-6410
Date of First Compliant Deposit:	27 August 2021
Date of Acceptance:	17 July 2020
Last Modified:	08 May 2023 18:48
URI:	https://orca.cardiff.ac.uk/id/eprint/143740

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