Details
| Original language | English |
|---|---|
| Pages (from-to) | 70-77 |
| Number of pages | 8 |
| Journal | Hypertension |
| Volume | 71 |
| Issue number | 1 |
| Early online date | 27 Nov 2017 |
| Publication status | Published - Jan 2018 |
| Externally published | Yes |
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
ASJC Scopus subject areas
- Medicine(all)
- Internal Medicine
Sustainable Development Goals
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In: Hypertension, Vol. 71, No. 1, 01.2018, p. 70-77.
Research output: Contribution to journal › Article › Research › peer review
}
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
UR - http://www.scopus.com/inward/record.url?scp=85038373677&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.117.10224
DO - 10.1161/HYPERTENSIONAHA.117.10224
M3 - Article
C2 - 29180454
AN - SCOPUS:85038373677
VL - 71
SP - 70
EP - 77
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 1
ER -