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Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension

Engeli, S. and Stinkens, R. and Heise, T. and May, M. and Goossens, G.H. and Blaak, E.E. and Jax, T. and Albrecht, D. and Pal, P. and Tegtbur, U. and Haufe, S. and Langenickel, T.H. and Jordan, J. (2018) Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension. Hypertension, 71, pp. 70-77. American Heart Association, Inc.. DOI: 10.1161/HYPERTENSIONAHA.117.10224 ISSN 0194-911X

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Official URL: http://hyper.ahajournals.org

Abstract

Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin inhibitor, was recently approved for the treatment of heart failure with reduced ejection fraction. Neprilysin degrades several peptides that modulate lipid metabolism, including natriuretic peptides. In this study, we investigated the effects of 8 weeks’ treatment with sacubitril/valsartan on whole-body and adipose tissue lipolysis and lipid oxidation during defned physical exercise compared with the metabolically neutral comparator amlodipine. This was a multicenter, randomized, double-blind, active-controlled, parallel-group study enrolling subjects with abdominal obesity and moderate hypertension (mean sitting systolic blood pressure ≥130–180 mmHg). Lipolysis during rest and exercise was assessed by microdialysis and [1,1,2,3,3-2H]-glycerol tracer kinetics. Energy expenditure and substrate oxidation were measured simultaneously using indirect calorimetry. Plasma nonesterifed fatty acids, glycerol, insulin, glucose, adrenaline and noradrenaline concentrations, blood pressure, and heart rate were also determined. Exercise elevated plasma glycerol, free fatty acids, and interstitial glycerol concentrations and increased the rate of glycerol appearance. However, exercise-induced stimulation of lipolysis was not augmented on sacubitril/valsartan treatment compared with amlodipine treatment. Furthermore, sacubitril/valsartan did not alter energy expenditure and substrate oxidation during exercise compared with amlodipine treatment. In conclusion, sacubitril/valsartan treatment for 8 weeks did not elicit clinically relevant changes in exercise-induced lipolysis or substrate oxidation in obese patients with hypertension, implying that ist benefcial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise.

Item URL in elib:https://elib.dlr.de/124121/
Document Type:Article
Title:Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Engeli, S.Hannover Medical School, Hannover, GermanyUNSPECIFIED
Stinkens, R.Department of Human Biology, NetherlandsUNSPECIFIED
Heise, T.Profil, Neuss, GermanyUNSPECIFIED
May, M.Institute for Clinical Pharmacology, MHH, GermanyUNSPECIFIED
Goossens, G.H.Department of Human Biology, NetherlandsUNSPECIFIED
Blaak, E.E.Department of Human Biology, NetherlandsUNSPECIFIED
Jax, T.Profil, GermanyUNSPECIFIED
Albrecht, D.Translational Medicine Novartis, SwitzerlandUNSPECIFIED
Pal, P.Biostatistical Sciences, Novartis, IndiaUNSPECIFIED
Tegtbur, U.UNSPECIFIEDUNSPECIFIED
Haufe, S.Hannover Medical School, Hannover, GermanyUNSPECIFIED
Langenickel, T.H.Translational Medicine, Novartis, SwitzerlandUNSPECIFIED
Jordan, J.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIED
Date:2018
Journal or Publication Title:Hypertension
Refereed publication:Yes
Open Access:Yes
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:71
DOI :10.1161/HYPERTENSIONAHA.117.10224
Page Range:pp. 70-77
Publisher:American Heart Association, Inc.
ISSN:0194-911X
Status:Published
Keywords:exercise-induced lipolysis; hypertension; lipid metabolism; natriuretic peptide, neprilysin; obesity; sacubitril/valsartan
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Systemphysiologie
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Cardiovascular Medicine in Aerospace
Deposited By: Schrage, Larissa
Deposited On:06 Dec 2018 14:20
Last Modified:06 Sep 2019 15:19

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