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Hypertension. 2018 Jan;71(1):70-77. doi: 10.1161/HYPERTENSIONAHA.117.10224. Epub 2017 Nov 27.

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

Author information

1
From the Institute of Clinical Pharmacology (S.E., M.M., S.H., J.J.), Institute of Sports Medicine (U.T.), Hannover Medical School, Germany; Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism (R.S., G.H.G., E.E.B.), Division of Endocrinology, Department of Internal Medicine (B.H.), Maastricht University Medical Center, The Netherlands; Profil, Neuss, Germany (T.H., T.J.); Translational Medicine, Novartis Pharma AG, Basel, Switzerland (D.A., T.H.L.); Biostatistical Sciences, Integrated Development Functions and Regions, Novartis Healthcare Pvt. Ltd, Hyderabad, India (P.P.); and Institute of Aerospace Medicine, German Aerospace Center (DLR) and Chair of Aerospace Medicine, University of Cologne, Germany (J.J.).
2
From the Institute of Clinical Pharmacology (S.E., M.M., S.H., J.J.), Institute of Sports Medicine (U.T.), Hannover Medical School, Germany; Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism (R.S., G.H.G., E.E.B.), Division of Endocrinology, Department of Internal Medicine (B.H.), Maastricht University Medical Center, The Netherlands; Profil, Neuss, Germany (T.H., T.J.); Translational Medicine, Novartis Pharma AG, Basel, Switzerland (D.A., T.H.L.); Biostatistical Sciences, Integrated Development Functions and Regions, Novartis Healthcare Pvt. Ltd, Hyderabad, India (P.P.); and Institute of Aerospace Medicine, German Aerospace Center (DLR) and Chair of Aerospace Medicine, University of Cologne, Germany (J.J.). jens.jordan@dlr.de.

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.

CLINICAL TRIAL REGISTRATION:

URL: https://www.clinicaltrials.gov. Unique identifier: NCT01631864.

KEYWORDS:

exercise-induced lipolysis; hypertension; lipid metabolism; natriuretic peptide, neprilysin; obesity; sacubitril/valsartan

PMID:
29180454
PMCID:
PMC5753808
DOI:
10.1161/HYPERTENSIONAHA.117.10224
[Indexed for MEDLINE]
Free PMC Article

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