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

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Stefan Engeli
  • Rudi Stinkens
  • Tim Heise
  • Marcus May
  • Gijs H. Goossens
  • Ellen E. Blaak
  • Bas Havekes
  • Thomas Jax
  • Diego Albrecht
  • Parasar Pal
  • Uwe Tegtbur
  • Sven Haufe
  • Thomas H. Langenickel
  • Jens Jordan

Externe Organisationen

  • Medizinische Hochschule Hannover (MHH)
  • Maastricht University
  • Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR)
  • Profil Institut für Stoffwechselforschung GmbH
  • Novartis AG
  • Novartis India Ltd.
Forschungs-netzwerk anzeigen

Details

OriginalspracheEnglisch
Seiten (von - bis)70-77
Seitenumfang8
FachzeitschriftHypertension
Jahrgang71
Ausgabenummer1
Frühes Online-Datum27 Nov. 2017
PublikationsstatusVeröffentlicht - Jan. 2018
Extern publiziertJa

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 defined 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 mm Hg). 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 nonesterified 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 its beneficial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise.

ASJC Scopus Sachgebiete

Ziele für nachhaltige Entwicklung

Zitieren

Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients with Obesity and Hypertension. / Engeli, Stefan; Stinkens, Rudi; Heise, Tim et al.
in: Hypertension, Jahrgang 71, Nr. 1, 01.2018, S. 70-77.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Engeli, S, Stinkens, R, Heise, T, May, M, Goossens, GH, Blaak, EE, Havekes, B, Jax, T, Albrecht, D, Pal, P, Tegtbur, U, Haufe, S, Langenickel, TH & Jordan, J 2018, 'Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients with Obesity and Hypertension', Hypertension, Jg. 71, Nr. 1, S. 70-77. https://doi.org/10.1161/HYPERTENSIONAHA.117.10224
Engeli, S., Stinkens, R., Heise, T., May, M., Goossens, G. H., Blaak, E. E., Havekes, B., Jax, T., Albrecht, D., Pal, P., Tegtbur, U., Haufe, S., Langenickel, T. H., & Jordan, J. (2018). Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients with Obesity and Hypertension. Hypertension, 71(1), 70-77. https://doi.org/10.1161/HYPERTENSIONAHA.117.10224
Engeli S, Stinkens R, Heise T, May M, Goossens GH, Blaak EE et al. Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients with Obesity and Hypertension. Hypertension. 2018 Jan;71(1):70-77. Epub 2017 Nov 27. doi: 10.1161/HYPERTENSIONAHA.117.10224
Engeli, Stefan ; Stinkens, Rudi ; Heise, Tim et al. / Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients with Obesity and Hypertension. in: Hypertension. 2018 ; Jahrgang 71, Nr. 1. S. 70-77.
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title = "Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients with Obesity and Hypertension",
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 defined 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 mm Hg). 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 nonesterified 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 its beneficial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise.",
keywords = "exercise-induced lipolysis, hypertension, lipid metabolism, natriuretic peptide, neprilysin, obesity, sacubitril/valsartan",
author = "Stefan Engeli and Rudi Stinkens and Tim Heise and Marcus May and Goossens, {Gijs H.} and Blaak, {Ellen E.} and Bas Havekes and Thomas Jax and Diego Albrecht and Parasar Pal and Uwe Tegtbur and Sven Haufe and Langenickel, {Thomas H.} and Jens Jordan",
note = "Funding Information: This study was funded by Novartis Pharma AG, Basel, Switzerland. Funding Information: S. Engeli has received significant financial support to conduct clinical studies from Novartis and Boehringer-Ingelheim, and modest lecture fees from Pfizer. T. Heise reports speaker honoraria and travel grants from Eli Lilly, Mylan and Novo Nordisk, honoraria for advisory panels from Novo Nordisk; and through Profil received research funds from Adocia, Astra Zeneca, Becton Dickinson, Biocon, Boehringer-Ingelheim, Dance Pharmaceuticals, Eli Lilly, Gr{\"u}nenthal, Gulf Pharmaceuticals, Johnson & Johnson, Marvel, Medimmune, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, Senseonics, and Zealand Pharma. J. Jordan served as consultant for Novartis, Boehringer-Ingelheim, Sanofi, Orexigen, Riemser, and Vivus; and is cofounder of Eternygen GmbH. D. Albrecht, P. Pal, and T.H. Langenickel are employees of Novartis. The other authors report no conflicts. ",
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Download

TY - JOUR

T1 - Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients with Obesity and Hypertension

AU - Engeli, Stefan

AU - Stinkens, Rudi

AU - Heise, Tim

AU - May, Marcus

AU - Goossens, Gijs H.

AU - Blaak, Ellen E.

AU - Havekes, Bas

AU - Jax, Thomas

AU - Albrecht, Diego

AU - Pal, Parasar

AU - Tegtbur, Uwe

AU - Haufe, Sven

AU - Langenickel, Thomas H.

AU - Jordan, Jens

N1 - Funding Information: This study was funded by Novartis Pharma AG, Basel, Switzerland. Funding Information: S. Engeli has received significant financial support to conduct clinical studies from Novartis and Boehringer-Ingelheim, and modest lecture fees from Pfizer. T. Heise reports speaker honoraria and travel grants from Eli Lilly, Mylan and Novo Nordisk, honoraria for advisory panels from Novo Nordisk; and through Profil received research funds from Adocia, Astra Zeneca, Becton Dickinson, Biocon, Boehringer-Ingelheim, Dance Pharmaceuticals, Eli Lilly, Grünenthal, Gulf Pharmaceuticals, Johnson & Johnson, Marvel, Medimmune, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, Senseonics, and Zealand Pharma. J. Jordan served as consultant for Novartis, Boehringer-Ingelheim, Sanofi, Orexigen, Riemser, and Vivus; and is cofounder of Eternygen GmbH. D. Albrecht, P. Pal, and T.H. Langenickel are employees of Novartis. The other authors report no conflicts.

PY - 2018/1

Y1 - 2018/1

N2 - 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 defined 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 mm Hg). 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 nonesterified 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 its beneficial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise.

AB - 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 defined 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 mm Hg). 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 nonesterified 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 its beneficial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise.

KW - exercise-induced lipolysis

KW - hypertension

KW - lipid metabolism

KW - natriuretic peptide, neprilysin

KW - obesity

KW - sacubitril/valsartan

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U2 - 10.1161/HYPERTENSIONAHA.117.10224

DO - 10.1161/HYPERTENSIONAHA.117.10224

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VL - 71

SP - 70

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JO - Hypertension

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