TY - JOUR
T1 - Sex differences in circulating proteins in heart failure with preserved ejection fraction
AU - Stienen, Susan
AU - Ferreira, Joao Pedro
AU - Kobayashi, Masatake
AU - Preud'homme, Gregoire
AU - Dobre, Daniela
AU - Machu, Jean-Loup
AU - Duarte, Kevin
AU - Bresso, Emmanuel
AU - Devignes, Marie-Dominique
AU - Andres, Natalia Lopez
AU - Girerd, Nicolas
AU - Aakhus, Svend
AU - Ambrosio, Giuseppe
AU - Brunner-La Rocca, Hans-Peter
AU - Fontes-Carvalho, Ricardo
AU - Fraser, Alan G.
AU - van Heerebeek, Loek
AU - de Keulenaer, Gilles
AU - Marino, Paolo
AU - McDonald, Kenneth
AU - Mebazaa, Alexandre
AU - Papp, Zoltan
AU - Raddino, Riccardo
AU - Tschoepe, Carsten
AU - Paulus, Walter J.
AU - Zannad, Faiez
AU - Rossignol, Patrick
N1 - Funding Information:
This study was supported by a grant from the European Union (FP7-HEALTH-2010-MEDIA), by the French Programme Hospitalier de Recherche Clinique (PHRC), and by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program (reference: ANR-15-RHU-0004), the GEENAGE (ANR-15-IDEX-04-LUE) program, by the Contrat de Plan Etat Région Lorraine and FEDER IT2MP. N-LA was supported by a Miguel Servet contract CP13/00221 from the “Insti-tuto de Salud Carlos III-FEDER”. WJP and LvH were supported by CVON, Dutch Heart Foundation, The Hague, The Netherlands (RECONNECT and EARLY-HFpEF projects). AM received speaker’s honoraria from Orion, Otsuka, Philips, Roche, and Servier. AM received fees as a member of the advisory board and/or Steering Committee and/or research grant from Adrenomed, Epygon, Neurotronik, Roche, Sanofi, and Sphyngotec. AM owns shares in S-Form Pharma. SS acknowledges funding received from the European Society of Cardiology in the form of an ESC Research Grant (R-2018-18686).
Publisher Copyright:
© 2020 The Author(s).
PY - 2020/8/24
Y1 - 2020/8/24
N2 - 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.
AB - 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.
KW - ACUTE MYOCARDIAL-INFARCTION
KW - MATRIX METALLOPROTEINASES
KW - LIPOPROTEIN-LIPASE
KW - GENDER-DIFFERENCES
KW - LEPTIN
KW - WOMEN
KW - MORTALITY
KW - DATABASE
KW - MEN
KW - ATHEROSCLEROSIS
U2 - 10.1186/s13293-020-00322-7
DO - 10.1186/s13293-020-00322-7
M3 - Article
C2 - 32831121
SN - 2042-6410
VL - 11
JO - Biology of Sex Differences
JF - Biology of Sex Differences
IS - 1
M1 - 47
ER -