Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction.

Autor:	Alogna A; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Campus Virchow-Klinikum, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany., Koepp KE; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA., Sabbah M; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA., Espindola Netto JM; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA., Jensen MD; Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA., Kirkland JL; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA; Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota., Lam CSP; National Heart Centre Singapore and Duke-National University of Singapore, Singapore., Obokata M; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA., Petrie MC; BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom., Ridker PM; Center for Cardiovascular Disease Prevention, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sorimachi H; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA., Tchkonia T; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA., Voors A; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Redfield MM; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA., Borlaug BA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: borlaug.barry@mayo.edu.
Jazyk:	angličtina
Zdroj:	JACC. Heart failure [JACC Heart Fail] 2023 Nov; Vol. 11 (11), pp. 1549-1561. Date of Electronic Publication: 2023 Aug 09.
DOI:	10.1016/j.jchf.2023.06.031
Abstrakt:	Background: Interleukin (IL)-6 is a central inflammatory mediator and potential therapeutic target in heart failure (HF). Prior studies have shown that IL-6 concentrations are elevated in patients with HF, but much fewer data are available in heart failure with preserved ejection fraction (HFpEF). Objectives: This study aims to determine how IL-6 relates to changes in cardiac function, congestion, body composition, and exercise tolerance in HFpEF. Methods: Clinical, laboratory, body composition, exercise capacity, physiologic and health status data across 4 National Heart, Lung, and Blood Institute-sponsored trials were analyzed according to the tertiles of IL-6. Results: IL-6 was measured in 374 patients with HFpEF. Patients with highest IL-6 levels had greater body mass index; higher N-terminal pro-B-type natriuretic peptide, C-reactive protein, and tumor necrosis factor-α levels; worse renal function; and lower hemoglobin levels, and were more likely to have diabetes. Although cardiac structure and function measured at rest were similar, patients with HFpEF and highest IL-6 concentrations had more severely impaired peak oxygen consumption (12.3 ± 3.3 mL/kg/min 13.1 ± 3.1 mL/kg/min 14.4 ± 3.9 mL/kg/min, P < 0.0001) as well as 6-minute walk distance (276 ± 107 m vs 332 ± 106 m vs 352 ± 116 m, P < 0.0001), even after accounting for increases in IL-6 related to excess body mass. IL-6 concentrations were associated with increases in total body fat and trunk fat, more severe symptoms during submaximal exercise, and poorer patient-reported health status. Conclusions: IL-6 levels are commonly elevated in HFpEF, and are associated with greater symptom severity, poorer exercise capacity, and more upper body fat accumulation. These findings support testing the hypothesis that therapies that inhibit IL-6 in patients with HFpEF may improve clinical status. (Clinical Trial Registrations: Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure [RELAX], NCT00763867; Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction, NCT02053493; Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF, NCT02742129; Inorganic Nitrite to Enhance Benefits From Exercise Training in Heart Failure With Preserved Ejection Fraction [HFpEF], NCT02713126). Competing Interests: Funding Support and Author Disclosures Dr Borlaug is supported by R01 HL128526, U01 HL160226, and R01 HL162828, from the National Institutes of Health (NIH), and W81XWH2210245, from the U.S. Department of Defense. Dr Alogna is supported by the Deutsche Forschungsgemeinschaft (DFG; CRC 1470, Z01). Drs Kirkland and Tchkonia are supported by R37 AG013925, P01 AG062413, and R33 AG061456 from NIH, the Connor Fund, Robert J. and Theresa W. Ryan, and the Noaber Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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