Engeli, Stefan, Stinkens, Rudi, Heise, Tim, May, Marcus ORCID: 0000-0002-7513-4244, Goossens, Gijs H., Blaak, Ellen E., Havekes, Bas, Jax, Thomas, Albrecht, Diego, Pal, Parasar, Tegtbur, Uwe, Haufe, Sven, Langenickel, Thomas H. and Jordan, Jens (2018). Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension. Hypertension, 71 (1). S. 70 - 78. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1524-4563

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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 mmHg). Lipolysis during rest and exercise was assessed by microdialysis and [1,1,2,3,3-H-2]-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. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01631864.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Engeli, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stinkens, RudiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heise, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
May, MarcusUNSPECIFIEDorcid.org/0000-0002-7513-4244UNSPECIFIED
Goossens, Gijs H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blaak, Ellen E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Havekes, BasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jax, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Albrecht, DiegoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pal, ParasarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tegtbur, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haufe, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langenickel, Thomas H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jordan, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-205113
DOI: 10.1161/HYPERTENSIONAHA.117.10224
Journal or Publication Title: Hypertension
Volume: 71
Number: 1
Page Range: S. 70 - 78
Date: 2018
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Place of Publication: PHILADELPHIA
ISSN: 1524-4563
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INTERSTITIAL ANGIOTENSIN-II; BRAIN NATRIURETIC PEPTIDE; HEART-FAILURE; NEPRILYSIN INHIBITION; INSULIN-RESISTANCE; ADIPOSE-TISSUE; NORMAL-WEIGHT; LIPOLYSIS; VALSARTAN; SYSTEMMultiple languages
Peripheral Vascular DiseaseMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/20511

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