Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Engeli, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Stinkens, Rudi UNSPECIFIED UNSPECIFIED UNSPECIFIED Heise, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED May, Marcus UNSPECIFIED orcid.org/0000-0002-7513-4244 UNSPECIFIED Goossens, Gijs H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaak, Ellen E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Havekes, Bas UNSPECIFIED UNSPECIFIED UNSPECIFIED Jax, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Albrecht, Diego UNSPECIFIED UNSPECIFIED UNSPECIFIED Pal, Parasar UNSPECIFIED UNSPECIFIED UNSPECIFIED Tegtbur, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Haufe, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Langenickel, Thomas H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jordan, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language INTERSTITIAL ANGIOTENSIN-II; BRAIN NATRIURETIC PEPTIDE; HEART-FAILURE; NEPRILYSIN INHIBITION; INSULIN-RESISTANCE; ADIPOSE-TISSUE; NORMAL-WEIGHT; LIPOLYSIS; VALSARTAN; SYSTEM Multiple languages Peripheral Vascular Disease Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20511