Abstract
Aims: Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men. Methods and results: In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over-representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher left ventricular ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up-regulated in women, while 21/363 and 14/363 were up-regulated in men. In both cohorts, the strongest up-regulated biomarkers in women were leptin and fatty acid binding protein-4, compared to matrix metalloproteinase-3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over-representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuro-inflammatory response in men (all p < 0.0001). Conclusion: In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro-inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies.
| Original language | English |
|---|---|
| Pages (from-to) | 1532-1544 |
| Number of pages | 13 |
| Journal | European Journal of Heart Failure |
| Volume | 24 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sept 2022 |
| Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by a grant from the European Commission [FP7‐242209‐BIOSTAT‐CHF]. R.A.d.B. is supported by a grant from the European Research Council (ERC CoG 818715, SECRETE‐HF).
Funding Information:
B.T.S reports grants from the Dutch Heart Foundation (2019 T094), during the conduct of this study. R.A.d.B. received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche. J.G.F. is supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217) and reports personal fees from Abbott, Amgen, Novartis, Medtronic, Idorsia, Servier, AstraZeneca, Innolife, Torrent, Respicardia, grants and personal fees from Bayer, Bristol Myers Squibb, Vifor, Pharmacosmos, Cytokinetics, Johnson & Johsnon, Myokardia, Stealth Biopharmaceuticals, Viscardia, personal fees and non‐financial support from Boehringer‐Ingelheim, outside the submitted work. C.S.P.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from AstraZeneca, Bayer, Boston Scientific and Roche Diagnostics; has served as consultant or on the Advisory Board/ Steering Committee/Executive Committee for Actelion, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., Us2.ai, Janssen Research & Development LLC, Medscape, Merck, Novartis, Novo Nordisk, Radcliffe Group Ltd., Roche Diagnostics, Sanofi and WebMD Global LLC; and serves as co‐founder & non‐executive director of Us2.ai. G.F. has received lecture fees and/or is a Committee Member in trial sponsored by Boehringer Ingelheim, Bayer, Amgen, Novartis, Medtronic, Servier. M.M. has received personal honoraria for participation in trials' committees, advisory boards or speeches at sponsored symposia from Abbott Vascular, Amgen, AstraZeneca, Bayer, Vifor Pharma, Servier, WindTree Therapeutics. A.A.V. received personal fees from AstraZeneca and Novo Nordisk. The UMCG, which employs several of the authors, has received research grants from Roche Diagnostics and Novo Nordisk, and consultancy fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cytokinetics, Novartis, Merck. All other authors have nothing to disclose. Conflict of interest:
Funding Information:
This work was supported by a grant from the European Commission [FP7-242209-BIOSTAT-CHF]. R.A.d.B. is supported by a grant from the European Research Council (ERC CoG 818715, SECRETE-HF). Conflict of interest: B.T.S reports grants from the Dutch Heart Foundation (2019 T094), during the conduct of this study. R.A.d.B. received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche. J.G.F. is supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217) and reports personal fees from Abbott, Amgen, Novartis, Medtronic, Idorsia, Servier, AstraZeneca, Innolife, Torrent, Respicardia, grants and personal fees from Bayer, Bristol Myers Squibb, Vifor, Pharmacosmos, Cytokinetics, Johnson & Johsnon, Myokardia, Stealth Biopharmaceuticals, Viscardia, personal fees and non-financial support from Boehringer-Ingelheim, outside the submitted work. C.S.P.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from AstraZeneca, Bayer, Boston Scientific and Roche Diagnostics; has served as consultant or on the Advisory Board/ Steering Committee/Executive Committee for Actelion, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc., Us2.ai, Janssen Research & Development LLC, Medscape, Merck, Novartis, Novo Nordisk, Radcliffe Group Ltd., Roche Diagnostics, Sanofi and WebMD Global LLC; and serves as co-founder & non-executive director of Us2.ai. G.F. has received lecture fees and/or is a Committee Member in trial sponsored by Boehringer Ingelheim, Bayer, Amgen, Novartis, Medtronic, Servier. M.M. has received personal honoraria for participation in trials' committees, advisory boards or speeches at sponsored symposia from Abbott Vascular, Amgen, AstraZeneca, Bayer, Vifor Pharma, Servier, WindTree Therapeutics. A.A.V. received personal fees from AstraZeneca and Novo Nordisk. The UMCG, which employs several of the authors, has received research grants from Roche Diagnostics and Novo Nordisk, and consultancy fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cytokinetics, Novartis, Merck. All other authors have nothing to disclose.
Publisher Copyright:
© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.