Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men

Research output: Contribution to journalJournal articlepeer-review

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Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men. / Thonsgaard, Simon; Prickett, Timothy C. R.; Hansen, Lasse H.; Albrechtsen, Nicolai J. Wewer; Andersen, Ulrik Ø.; Terzic, Dijana; Plomgaard, Peter; Gustafsson, Finn; Goetze, Jens P.; Mark, Peter D.

In: Clinical Chemistry, Vol. 68, No. 5, 2022, p. 713–720.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Thonsgaard, S, Prickett, TCR, Hansen, LH, Albrechtsen, NJW, Andersen, UØ, Terzic, D, Plomgaard, P, Gustafsson, F, Goetze, JP & Mark, PD 2022, 'Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men', Clinical Chemistry, vol. 68, no. 5, pp. 713–720. https://doi.org/10.1093/clinchem/hvac005

APA

Thonsgaard, S., Prickett, T. C. R., Hansen, L. H., Albrechtsen, N. J. W., Andersen, U. Ø., Terzic, D., Plomgaard, P., Gustafsson, F., Goetze, J. P., & Mark, P. D. (2022). Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men. Clinical Chemistry, 68(5), 713–720. https://doi.org/10.1093/clinchem/hvac005

Vancouver

Thonsgaard S, Prickett TCR, Hansen LH, Albrechtsen NJW, Andersen UØ, Terzic D et al. Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men. Clinical Chemistry. 2022;68(5):713–720. https://doi.org/10.1093/clinchem/hvac005

Author

Thonsgaard, Simon ; Prickett, Timothy C. R. ; Hansen, Lasse H. ; Albrechtsen, Nicolai J. Wewer ; Andersen, Ulrik Ø. ; Terzic, Dijana ; Plomgaard, Peter ; Gustafsson, Finn ; Goetze, Jens P. ; Mark, Peter D. / Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men. In: Clinical Chemistry. 2022 ; Vol. 68, No. 5. pp. 713–720.

Bibtex

@article{42576ba5e9f44a35be3018bbafa50418,
title = "Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men",
abstract = "Background C-type natriuretic peptide (CNP) is a cardioprotective peptide with high affinity for the ectoenzyme neutral endopeptidase (neprilysin). We aimed to determine whether angiotensin receptor-neprilysin inhibitor treatment acutely affects circulating concentrations of bioactive CNP and its molecular amino-terminal precursor (NT-proCNP). Methods We included 9 and 10 healthy young men in 2 randomized crossover trials with sacubitril/valsartan vs control (Trial 1) and sacubitril/valsartan and sitagliptin vs sitagliptin (Trial 2). The participants were randomized to a single dose of sacubitril/valsartan (194/206 mg) or control at the first visit 30 min prior to a standardized meal intake. We obtained blood samples at 12 time points over 5 h and measured plasma concentrations of NT-proCNP in both trials and CNP in Trial 2. Results NT-proCNP concentrations increased 3.5 h after sacubitril/valsartan treatment, and at 4.5 h concentrations were 42% and 65% higher compared with control in Trial 1 and Trial 2, respectively. The total area under the curve (tAUC)(15-270 min) was 22% higher (P = 0.007) in Trial 1 and 17% higher with treatment (P = 0.017) in Trial 2. Concentrations of bioactive CNP followed a similar temporal pattern with an increase of 93% at 4.5 h and a 31% higher tAUC(15-270 min) compared with control (P = 0.001) in Trial 2. Conclusions Sacubitril/valsartan augments circulating concentrations of both bioactive CNP and NT-proCNP in healthy young men. The increase in bioactive CNP is most likely caused by de novo synthesis and secretion rather than diminished breakdown through neprilysin inhibition. ClinicalTrials.gov registration number NCT03717688",
keywords = "C-type natriuretic peptide, CNP, natriuretic peptides, NT-proCNP, sacubitril, valsartan, NEPRILYSIN INHIBITION, EXPRESSION, ENALAPRIL, RESPONSES",
author = "Simon Thonsgaard and Prickett, {Timothy C. R.} and Hansen, {Lasse H.} and Albrechtsen, {Nicolai J. Wewer} and Andersen, {Ulrik {\O}.} and Dijana Terzic and Peter Plomgaard and Finn Gustafsson and Goetze, {Jens P.} and Mark, {Peter D.}",
year = "2022",
doi = "10.1093/clinchem/hvac005",
language = "English",
volume = "68",
pages = "713–720",
journal = "Clinical Chemistry",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry, Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men

AU - Thonsgaard, Simon

AU - Prickett, Timothy C. R.

AU - Hansen, Lasse H.

AU - Albrechtsen, Nicolai J. Wewer

AU - Andersen, Ulrik Ø.

AU - Terzic, Dijana

AU - Plomgaard, Peter

AU - Gustafsson, Finn

AU - Goetze, Jens P.

AU - Mark, Peter D.

PY - 2022

Y1 - 2022

N2 - Background C-type natriuretic peptide (CNP) is a cardioprotective peptide with high affinity for the ectoenzyme neutral endopeptidase (neprilysin). We aimed to determine whether angiotensin receptor-neprilysin inhibitor treatment acutely affects circulating concentrations of bioactive CNP and its molecular amino-terminal precursor (NT-proCNP). Methods We included 9 and 10 healthy young men in 2 randomized crossover trials with sacubitril/valsartan vs control (Trial 1) and sacubitril/valsartan and sitagliptin vs sitagliptin (Trial 2). The participants were randomized to a single dose of sacubitril/valsartan (194/206 mg) or control at the first visit 30 min prior to a standardized meal intake. We obtained blood samples at 12 time points over 5 h and measured plasma concentrations of NT-proCNP in both trials and CNP in Trial 2. Results NT-proCNP concentrations increased 3.5 h after sacubitril/valsartan treatment, and at 4.5 h concentrations were 42% and 65% higher compared with control in Trial 1 and Trial 2, respectively. The total area under the curve (tAUC)(15-270 min) was 22% higher (P = 0.007) in Trial 1 and 17% higher with treatment (P = 0.017) in Trial 2. Concentrations of bioactive CNP followed a similar temporal pattern with an increase of 93% at 4.5 h and a 31% higher tAUC(15-270 min) compared with control (P = 0.001) in Trial 2. Conclusions Sacubitril/valsartan augments circulating concentrations of both bioactive CNP and NT-proCNP in healthy young men. The increase in bioactive CNP is most likely caused by de novo synthesis and secretion rather than diminished breakdown through neprilysin inhibition. ClinicalTrials.gov registration number NCT03717688

AB - Background C-type natriuretic peptide (CNP) is a cardioprotective peptide with high affinity for the ectoenzyme neutral endopeptidase (neprilysin). We aimed to determine whether angiotensin receptor-neprilysin inhibitor treatment acutely affects circulating concentrations of bioactive CNP and its molecular amino-terminal precursor (NT-proCNP). Methods We included 9 and 10 healthy young men in 2 randomized crossover trials with sacubitril/valsartan vs control (Trial 1) and sacubitril/valsartan and sitagliptin vs sitagliptin (Trial 2). The participants were randomized to a single dose of sacubitril/valsartan (194/206 mg) or control at the first visit 30 min prior to a standardized meal intake. We obtained blood samples at 12 time points over 5 h and measured plasma concentrations of NT-proCNP in both trials and CNP in Trial 2. Results NT-proCNP concentrations increased 3.5 h after sacubitril/valsartan treatment, and at 4.5 h concentrations were 42% and 65% higher compared with control in Trial 1 and Trial 2, respectively. The total area under the curve (tAUC)(15-270 min) was 22% higher (P = 0.007) in Trial 1 and 17% higher with treatment (P = 0.017) in Trial 2. Concentrations of bioactive CNP followed a similar temporal pattern with an increase of 93% at 4.5 h and a 31% higher tAUC(15-270 min) compared with control (P = 0.001) in Trial 2. Conclusions Sacubitril/valsartan augments circulating concentrations of both bioactive CNP and NT-proCNP in healthy young men. The increase in bioactive CNP is most likely caused by de novo synthesis and secretion rather than diminished breakdown through neprilysin inhibition. ClinicalTrials.gov registration number NCT03717688

KW - C-type natriuretic peptide

KW - CNP

KW - natriuretic peptides

KW - NT-proCNP

KW - sacubitril

KW - valsartan

KW - NEPRILYSIN INHIBITION

KW - EXPRESSION

KW - ENALAPRIL

KW - RESPONSES

U2 - 10.1093/clinchem/hvac005

DO - 10.1093/clinchem/hvac005

M3 - Journal article

C2 - 35175317

VL - 68

SP - 713

EP - 720

JO - Clinical Chemistry

JF - Clinical Chemistry

SN - 0009-9147

IS - 5

ER -

ID: 299034952