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Journal Articles Biology of Sex Differences Year : 2020

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

1 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
2 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
3 Cardiovascular & Renal Clinical Trialists - CRCT - French-Clinical Research Infrastructure Network - F-CRIN [Paris]
4 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
5 Universidade do Porto = University of Porto
6 CPN - Centre Psychothérapique de Nancy [Laxou]
7 CAPSID - Computational Algorithms for Protein Structures and Interactions
8 UPNA - Universidad Pública de Navarra [Espagne] = Public University of Navarra
9 Oslo University Hospital [Oslo]
10 NTNU - Norwegian University of Science and Technology [Trondheim]
11 Department of Medicine [Perugia, Italy]
12 Department of Cardiology, Maastricht University Medical Center
13 Department of Surgery and Physiology, Cardiovascular Research Unit (UnIC), Faculty of Medicine, University of Porto
14 WHRI - Wales Heart Research Institute [Cardiff]
15 Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam
16 UA - University of Antwerp
17 UPO - Università degli Studi del Piemonte Orientale - Amedeo Avogadro
18 St Michael's Hospital Dun Laoghaire Co. Dublin
19 MASCOT (UMR_S_942 / U942) - Marqueurs cardiovasculaires en situation de stress
20 Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière]
21 Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen
22 Department of Cardiology, Spedali Civili di Brescia
23 Charité Campus Virchow-Klinikum (CVK)
24 Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers


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.
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Dates and versions

hal-02928742 , version 1 (16-10-2020)





Susan Stienen, Joao Pedro Ferreira, Masatake Kobayashi, Gregoire Preud’homme, Daniela Dobre, et al.. Sex differences in circulating proteins in heart failure with preserved ejection fraction. Biology of Sex Differences, 2020, 11 (1), pp.47. ⟨10.1186/s13293-020-00322-7⟩. ⟨hal-02928742⟩
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