@article{a453b22b6997460b985922db9f4c12c6,
title = "Characterization of the inflammatory-metabolic phenotype of heart failure with a preserved ejection fraction: a hypothesis to explain influence of sex on the evolution and potential treatment of the disease",
abstract = "Accumulating evidence points to the existence of an inflammatory-metabolic phenotype of heart failure with a preserved ejection fraction (HFpEF), which is characterized by biomarkers of inflammation, an expanded epicardial adipose tissue mass, microvascular endothelial dysfunction, normal-to-mildly increased left ventricular volumes and systolic blood pressures, and possibly, altered activity of adipocyte-associated inflammatory mediators. A broad range of adipogenic metabolic and systemic inflammatory disorders – e.g. obesity, diabetes and metabolic syndrome as well as rheumatoid arthritis and psoriasis – can cause this phenotype, independent of the presence of large vessel coronary artery disease. Interestingly, when compared with men, women are both at greater risk of and may suffer greater cardiac consequences from these systemic inflammatory and metabolic disorders. Women show disproportionate increases in left ventricular filling pressures following increases in central blood volume and have greater arterial stiffness than men. Additionally, they are particularly predisposed to epicardial and intramyocardial fat expansion and imbalances in adipocyte-associated proinflammatory mediators. The hormonal interrelationships seen in inflammatory-metabolic phenotype may explain why mineralocorticoid receptor antagonists and neprilysin inhibitors may be more effective in women than in men with HFpEF. Recognition of the inflammatory-metabolic phenotype may improve an understanding of the pathogenesis of HFpEF and enhance the ability to design clinical trials of interventions in this heterogeneous syndrome.",
keywords = "Aldosterone, Diabetes, Heart failure with preserved ejection fraction, Neprilysin, Obesity, Systemic inflammation",
author = "Milton Packer and Lam, {Carolyn S.P.} and Lund, {Lars H.} and Maurer, {Mathew S.} and Borlaug, {Barry A.}",
note = "Funding Information: M.P. has recently consulted for Abbvie, Actavis, Akcea, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiorentis, Daiichi‐Sankyo, Gilead, Johnson & Johnson, NovoNordisk, Pfizer, Relypsa, Sanofi, Synthetic Biologics and Theravance. None of these relationships are related to this work or to the topic of this manuscript. C.S.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on the Advisory Board/ Steering Committee/Executive Committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research & Development LLC, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, WebMD Global LLC, Radcliffe Group Ltd and Corpus. None of these relationships are related to this work or to the topic of this manuscript. L.H.L. reports personal fees from Abbott, AstraZeneca, Bayer, Medscape, Merck, Mundipharma, Novartis, Pharmacosmos, Relypsa, Sanofi and Vifor‐Fresenius and grants from AstraZeneca, Boehringer Ingelehim, Boston Scientific, Mundipharma, Novartis, Relypsa and Vifor‐Frenenius. None of these relationships are related to this work or to the topic of this manuscript. M.S.M. receives grant support from NIH R01HL139671–01, R21AG058348 and K24AG036778. He has had consulting income from Pfizer, GSK, EIdos, Prothena, Akcea and Alnylam, and institution received clinical trial funding from Pfizer, Prothena, Eidos and Alnylam. None of these relationships are related to this work or to the topic of this manuscript. B.A.B. has received grant support from the NIH/NHLBI (RO1 HL128526 and U10 HL110262), Medtronic, Tenax, GlaxoSmithKline, Mesoblast, AstraZeneca, Novartis, Corvia. Conflict of interest: Publisher Copyright: {\textcopyright} 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.",
year = "2020",
month = sep,
day = "1",
doi = "10.1002/ejhf.1902",
language = "English (US)",
volume = "22",
pages = "1551--1567",
journal = "European Journal of Heart Failure",
issn = "1388-9842",
publisher = "Oxford University Press",
number = "9",
}