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Brain natriuretic peptide 32

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Brain natriuretic peptide (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume.[5] BNP is one of the three natriuretic peptides, in addition to atrial natriuretic peptide (ANP) and C-type natriuretic peptide ( CNP).[6] BNP was first discovered in porcine brain tissue in 1988, which led to its initial naming as "brain natriuretic peptide", although subsequent research revealed that BNP is primarily produced and secreted by the ventricular myocardium (heart muscle) in response to increased ventricular blood volume and stretching. To reflect its true source, BNP is now often referred to as "B-type natriuretic peptide" while retaining the same acronym. [7]

NPPB
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNPPB, natriuretic peptide B, BNP, Iso-ANP, ventricular natriuretic peptide
External IDsOMIM: 600295; MGI: 97368; HomoloGene: 81698; GeneCards: NPPB; OMA:NPPB - orthologs
Orthologs
SpeciesHumanMouse
Entrez

4879

18158

Ensembl

ENSG00000120937

ENSMUSG00000029019

UniProt

P16860

P40753

RefSeq (mRNA)

NM_002521

NM_001287348
NM_008726

RefSeq (protein)

NP_002512
NP_002512

NP_001274277
NP_032752

Location (UCSC)Chr 1: 11.86 – 11.86 MbChr 4: 148.07 – 148.07 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The 32-amino acid polypeptide BNP-32 is secreted attached to a 76–amino acid N-terminal fragment in the prohormone called NT-proBNP (BNPT), which is biologically inactive. Once released, BNP binds to and activates the atrial natriuretic factor receptor NPRA, and to a lesser extent NPRB, in a fashion similar to atrial natriuretic peptide (ANP) but with 10-fold lower affinity. The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing.

The physiologic actions of BNP are similar to those of ANP and include decrease in systemic vascular resistance and central venous pressure as well as an increase in natriuresis. The net effect of these peptides is a decrease in blood pressure due to the decrease in systemic vascular resistance and, thus, afterload. Additionally, the actions of both BNP and ANP result in a decrease in cardiac output due to an overall decrease in central venous pressure and preload as a result of the reduction in blood volume that follows natriuresis and diuresis.[8]

Biosynthesis

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BNP is synthesized as a 134-amino acid preprohormone (preproBNP), encoded by the human gene NPPB. Removal of the 26-residue N-terminal signal peptide generates the prohormone, proBNP, which is stored intracellularly as an O-linked glycoprotein; proBNP is subsequently cleaved between arginine-102 and serine-103 by a specific convertase (probably furin or corin) into NT-proBNP and the biologically active 32-amino acid polypeptide BNP-32, which are secreted into the blood in equimolar amounts.[9][10] Cleavage at other sites produces shorter BNP peptides with unknown biological activity.[11] Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites.[12] The synthesis of BNP in cardiomyocytes is stimulated by pro-inflammatory cell factors, such as interleukin-1β, interleukin-6 and tumor necrosis factor-α.[13]

Physiologic effects

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Renal

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Adrenal

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  • Reduces aldosterone secretion by the zona glomerulosa of the adrenal cortex.

Vascular

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Relaxes vascular smooth muscle in arterioles and venules by:

  • Membrane Receptor-mediated elevation of vascular smooth muscle cGMP
  • Inhibition of the effects of catecholamines

Promotes uterine spiral artery remodeling, which is important for preventing pregnancy-induced hypertension.[16]

Cardiac

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  • Inhibits maladaptive cardiac hypertrophy
  • Mice lacking cardiac NPRA develop increased cardiac mass and severe fibrosis and die suddenly[17]
  • Re-expression of NPRA rescues the phenotype.

Adipose tissue

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  • Increases the release of free fatty acids from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
  • Activates adipocyte plasma membrane type A guanylyl cyclase receptors NPR-A
  • Increases intracellular cGMP levels that induce the phosphorylation of a hormone-sensitive lipase and perilipin A via the activation of a cGMP-dependent protein kinase-I (cGK-I)
  • Does not modulate cAMP production or PKA activity

Measurement

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BNP and NT-proBNP are measured by immunoassay.[18]

Interpretation of BNP

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  • The main clinical utility of either BNP or NT-proBNP is that a normal level helps to rule out chronic heart failure in the emergency setting. An elevated BNP or NT-proBNP should never be used exclusively to "rule in" acute or chronic heart failure in the emergency setting due to lack of specificity [dubious – discuss].[19]
  • Either BNP or NT-proBNP can also be used for screening and prognosis of heart failure.[20]
  • Increased NT-proBNP adjusted for age and sex and annual increase of NT-proBNP above 50% are associated with increased event rate in patients with non-severe aortic valve stenosis.[21]
  • BNP and NT-proBNP are also typically increased in patients with left ventricular dysfunction, with or without symptoms (BNP accurately reflects current ventricular status, as its half-life is 20 minutes, as opposed to 1–2 hours for NT-proBNP).[22]

A preoperative BNP can be predictive of a risk of an acute cardiac event during vascular surgery. A cutoff of 100 pg/ml has a sensitivity of approximately 100%, a negative predictive value of approximately 100%, a specificity of 90%, and a positive predictive value of 78% according to data from the United Kingdom.[23]

BNP is cleared by binding to natriuretic peptide receptors (NPRs) and neutral endopeptidase (NEP). Less than 5% of BNP is cleared renally. NT-proBNP is the inactive molecule resulting from cleavage of the prohormone Pro-BNP and is reliant solely on the kidney for excretion. The achilles heel of the NT-proBNP molecule is the overlap in kidney disease in the heart failure patient population.[24][25]

Some laboratories report in units ng per Litre (ng/L), which is equivalent to pg/mL

There is a diagnostic 'gray area', often defined as between 100 and 500 pg/mL, for which the test is considered inconclusive, but, in general, levels above 500 pg/ml are considered to be an indicator of heart failure. This so-called gray zone has been addressed in several studies, and using clinical history or other available simple tools can help make the diagnosis.[26][27]

BNP has been suggested as a predictor for a variety of medical states, including cardiovascular mortality in diabetics[28] and cardiac impairment in cancer patients.[29][30]

BNP was found to have an important role in prognostication of heart surgery patients[31] and in the emergency department.[32] It has been shown that combining BNP with other tools like impedance cardiography (ICG) can improve early diagnosis of heart failure and advance prevention strategies.[33][34] Utility of BNP has also been explored in various settings like preeclampsia, intensive care, shock and end-stage renal disease (ESRD).[35][36][37]

The effect or race and gender on value of BNP and its utility in that context has been studied extensively.[38][39]

NT-proBNP levels (in pg/mL) by New York Heart Association Functional Classification (NYHA functional class)[40]
NYHA I NYHA II NYHA III NYHA IV
5th Percentile 33 103 126 148
Mean 1015 1666 3029 3465
95th Percentile 3410 6567 10,449 12,188

The BNP test is used as an aid in the diagnosis and assessment of severity of heart failure. A recent meta-analysis concerning effects of BNP testing on clinical outcomes of patients presenting to the emergency department with acute dyspnea revealed that BNP testing led to a decrease in admission rates and decrease in mean length of stay, although neither was statistically significant. Effects on all cause hospital mortality was inconclusive.[41] The BNP test is also used for the risk stratification of patients with acute coronary syndromes.[42][43]

When interpreting an elevated BNP level, values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients.[44] Higher levels are seen in those with renal disease, in the absence of heart failure.

Therapeutic application

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Recombinant BNP, nesiritide, has been suggested as a treatment for decompensated heart failure. However, a clinical trial failed to show a benefit of nesiritide in patients with acute decompensated heart failure.[45] Blockade of neprilysin, a protease known to degrade members of the natriuretic peptide family, has also been suggested as a possible treatment for heart failure. Dual administration of neprilysin inhibitors and angiotensin receptor blockers has been shown to be advantageous to ACE inhibitors, the current first-line therapy, in multiple settings.[46][47]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000120937 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029019 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Potter LR, Yoder AR, Flora DR, Antos LK, Dickey DM (2009). Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications. Handbook of Experimental Pharmacology. Vol. 191. pp. 341–66. doi:10.1007/978-3-540-68964-5_15. ISBN 978-3-540-68960-7. PMC 4855512. PMID 19089336.
  6. ^ Potter LR, Yoder AR, Flora DR, Antos LK, Dickey DM (2009). "Natriuretic Peptides: Their Structures, Receptors, Physiologic Functions and Therapeutic Applications". CGMP: Generators, Effectors and Therapeutic Implications. Handbook of Experimental Pharmacology. Vol. 191. pp. 341–366. doi:10.1007/978-3-540-68964-5_15. ISBN 978-3-540-68960-7. ISSN 0171-2004. PMC 4855512. PMID 19089336.
  7. ^ Potter LR (2009). "Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications". Handb Exp Pharmacol (191): 341–66.
  8. ^ "CV Pharmacology - Natriuretic Peptides". cvpharmacology.com. Archived from the original on 21 October 2017. Retrieved 29 April 2018.
  9. ^ Ichiki T, Burnett JC (2010-07-20). "A new signal from B-type natriuretic peptide in ST-elevation myocardial infarction: what does it mean for B-type natriuretic peptide and innovative diagnostics?". Circulation. 122 (3): 229–232. doi:10.1161/CIRCULATIONAHA.110.966358. ISSN 1524-4539. PMC 3835654. PMID 20606114.
  10. ^ Schellenberger U, O'Rear J, Guzzetta A, Jue RA, Protter AA, Pollitt NS (July 2006). "The precursor to B-type natriuretic peptide is an O-linked glycoprotein". Archives of Biochemistry and Biophysics. 451 (2): 160–6. doi:10.1016/j.abb.2006.03.028. PMID 16750161.
  11. ^ Niederkofler EE, Kiernan UA, O'Rear J, Menon S, Saghir S, Protter AA, et al. (November 2008). "Detection of endogenous B-type natriuretic peptide at very low concentrations in patients with heart failure". Circulation: Heart Failure. 1 (4): 258–64. doi:10.1161/CIRCHEARTFAILURE.108.790774. PMID 19808300.
  12. ^ Semenov AG, Postnikov AB, Tamm NN, Seferian KR, Karpova NS, Bloshchitsyna MN, et al. (March 2009). "Processing of pro-brain natriuretic peptide is suppressed by O-glycosylation in the region close to the cleavage site". Clinical Chemistry. 55 (3): 489–98. doi:10.1373/clinchem.2008.113373. PMID 19168558.
  13. ^ Fu S, Ping P, Wang F, Luo L (December 2018). "Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure". Journal of Biological Engineering. 12 (1): 2. doi:10.1186/s13036-017-0093-0. PMC 5766980. PMID 29344085.
  14. ^ Kiberd BA, Larson TS, Robertson CR, Jamison RL (June 1987). "Effect of atrial natriuretic peptide on vasa recta blood flow in the rat". The American Journal of Physiology. 252 (6 Pt 2): F1112-7. doi:10.1152/ajprenal.1987.252.6.F1112. PMID 2954471.
  15. ^ Reeves WB, Andreoli TE (2008). "Chapter 31 – Sodium Chloride Transport in the Loop of Henle, Distal Convoluted Tubule, and Collecting Duct". In Giebisch GH, Alpern RA, Herbert SC, Seldin DW (eds.). Seldin and Giebisch's the kidney: physiology and pathophysiology. Amsterdam: Elsevier/Academic Press. pp. 849–887. doi:10.1016/B978-012088488-9.50034-6. ISBN 978-0-12-088488-9.
  16. ^ Cui Y, Wang W, Dong N, Lou J, Srinivasan DK, Cheng W, et al. (March 2012). "Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy". Nature. 484 (7393): 246–50. Bibcode:2012Natur.484..246C. doi:10.1038/nature10897. PMC 3578422. PMID 22437503.
  17. ^ Tamura N, Ogawa Y, Chusho H, Nakamura K, Nakao K, Suda M, et al. (April 2000). "Cardiac fibrosis in mice lacking brain natriuretic peptide". Proceedings of the National Academy of Sciences of the United States of America. 97 (8): 4239–44. Bibcode:2000PNAS...97.4239T. doi:10.1073/pnas.070371497. PMC 18212. PMID 10737768.
  18. ^ Clerico A, Zaninotto M, Prontera C, Giovannini S, Ndreu R, Franzini M, et al. (December 2012). "State of the art of BNP and NT-proBNP immunoassays: the CardioOrmoCheck study". Clinica Chimica Acta; International Journal of Clinical Chemistry. 414: 112–9. doi:10.1016/j.cca.2012.07.017. hdl:11382/365432. PMID 22910582.
  19. ^ Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, et al. (July 2002). "Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure". The New England Journal of Medicine. 347 (3): 161–7. doi:10.1056/NEJMoa020233. PMID 12124404.
  20. ^ Bhalla V, Willis S, Maisel AS (2004). "B-type natriuretic peptide: the level and the drug--partners in the diagnosis of congestive heart failure". Congestive Heart Failure. 10 (1 Suppl 1): 3–27. doi:10.1111/j.1527-5299.2004.03310.x. PMID 14872150.
  21. ^ Hadziselimovic E, Greve AM, Sajadieh A, Olsen MH, Kesäniemi YA, Nienaber CA, et al. (2022-04-01). "Association of Annual N-Terminal Pro-Brain Natriuretic Peptide Measurements With Clinical Events in Patients With Asymptomatic Nonsevere Aortic Stenosis: A Post Hoc Substudy of the SEAS Trial". JAMA Cardiology. 7 (4): 435–444. doi:10.1001/jamacardio.2021.5916. ISSN 2380-6583. PMC 8851368. PMID 35171199.
  22. ^ Atisha D, Bhalla MA, Morrison LK, Felicio L, Clopton P, Gardetto N, et al. (September 2004). "A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction". American Heart Journal. 148 (3): 518–23. doi:10.1016/j.ahj.2004.03.014. PMID 15389242.
  23. ^ Berry C, Kingsmore D, Gibson S, Hole D, Morton JJ, Byrne D, et al. (March 2006). "Predictive value of plasma brain natriuretic peptide for cardiac outcome after vascular surgery". Heart. 92 (3): 401–2. doi:10.1136/hrt.2005.060988. PMC 1860808. PMID 16501204.
  24. ^ Austin WJ, Bhalla V, Hernandez-Arce I, Isakson SR, Beede J, Clopton P, et al. (October 2006). "Correlation and prognostic utility of B-type natriuretic peptide and its amino-terminal fragment in patients with chronic kidney disease". American Journal of Clinical Pathology. 126 (4): 506–12. doi:10.1309/M7AAXA0J1THMNCDF. PMID 16938661.
  25. ^ Daniels LB, Clopton P, Bhalla V, Krishnaswamy P, Nowak RM, McCord J, et al. (May 2006). "How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study". American Heart Journal. 151 (5): 999–1005. doi:10.1016/j.ahj.2005.10.011. PMID 16644321.
  26. ^ Strunk A, Bhalla V, Clopton P, Nowak RM, McCord J, Hollander JE, et al. (January 2006). "Impact of the history of congestive heart failure on the utility of B-type natriuretic peptide in the emergency diagnosis of heart failure: results from the Breathing Not Properly Multinational Study". The American Journal of Medicine. 119 (1): 69.e1–11. doi:10.1016/j.amjmed.2005.04.029. PMID 16431187.
  27. ^ Brenden CK, Hollander JE, Guss D, McCullough PA, Nowak R, Green G, et al. (May 2006). "Gray zone BNP levels in heart failure patients in the emergency department: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study". American Heart Journal. 151 (5): 1006–11. doi:10.1016/j.ahj.2005.10.017. PMID 16644322.
  28. ^ Bhalla MA, Chiang A, Epshteyn VA, Kazanegra R, Bhalla V, Clopton P, et al. (September 2004). "Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus". Journal of the American College of Cardiology. 44 (5): 1047–52. doi:10.1016/j.jacc.2004.05.071. PMID 15337217.
  29. ^ Palumbo I, Palumbo B, Fravolino M, et al. (2016). "Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: A prospective study". The Breast. 25: 45–50. doi:10.1016/j.breast.2015.10.004. PMID 26547836.
  30. ^ Bando S, Soeki T, Matsuura T, et al. (2017). "Plasma brain natriuretic peptide levels are elevated in patients with cancer". PLOS ONE. 12 (6): e0178607. Bibcode:2017PLoSO..1278607B. doi:10.1371/journal.pone.0178607. PMC 5453551. PMID 28570595.
  31. ^ Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, et al. (May 2004). "Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery". Journal of the American College of Cardiology. 43 (10): 1873–9. doi:10.1016/j.jacc.2003.12.048. PMID 15145114.
  32. ^ Maisel A, Hollander JE, Guss D, McCullough P, Nowak R, Green G, et al. (September 2004). "Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath". Journal of the American College of Cardiology. 44 (6): 1328–33. doi:10.1016/j.jacc.2004.06.015. PMID 15364340.
  33. ^ Bhalla V, Isakson S, Bhalla MA, Lin JP, Clopton P, Gardetto N, et al. (February 2005). "Diagnostic ability of B-type natriuretic peptide and impedance cardiography: testing to identify left ventricular dysfunction in hypertensive patients". American Journal of Hypertension. 18 (2 Pt 2): 73S–81S. doi:10.1016/j.amjhyper.2004.11.044. PMID 15752936.
  34. ^ Castellanos LR, Bhalla V, Isakson S, Daniels LB, Bhalla MA, Lin JP, et al. (February 2009). "B-type natriuretic peptide and impedance cardiography at the time of routine echocardiography predict subsequent heart failure events". Journal of Cardiac Failure. 15 (1): 41–7. doi:10.1016/j.cardfail.2008.09.003. PMID 19181293.
  35. ^ Resnik JL, Hong C, Resnik R, Kazanegra R, Beede J, Bhalla V, et al. (August 2005). "Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women". American Journal of Obstetrics and Gynecology. 193 (2): 450–4. doi:10.1016/j.ajog.2004.12.006. PMID 16098869.
  36. ^ Bhalla V, Bhalla MA, Maisel AS (August 2004). "Evolution of B-type natriuretic peptide in evaluation of intensive care unit shock". Critical Care Medicine. 32 (8): 1787–9. doi:10.1097/01.CCM.0000135748.75590.54. PMID 15286561.
  37. ^ Sheen V, Bhalla V, Tulua-Tata A, Bhalla MA, Weiss D, Chiu A, et al. (February 2007). "The use of B-type natriuretic peptide to assess volume status in patients with end-stage renal disease". American Heart Journal. 153 (2): 244.e1–5. doi:10.1016/j.ahj.2006.10.041. PMID 17239684.
  38. ^ Maisel AS, Clopton P, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, et al. (June 2004). "Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study". American Heart Journal. 147 (6): 1078–84. doi:10.1016/j.ahj.2004.01.013. PMID 15199359.
  39. ^ Daniels LB, Bhalla V, Clopton P, Hollander JE, Guss D, McCullough PA, et al. (May 2006). "B-type natriuretic peptide (BNP) levels and ethnic disparities in perceived severity of heart failure: results from the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT) multicenter study of BNP levels and emergency department decision making in patients presenting with shortness of breath". Journal of Cardiac Failure. 12 (4): 281–5. doi:10.1016/j.cardfail.2006.01.008. PMID 16679261.
  40. ^ "N-terminal-pro-BNP". LABORATORY SERVICES HANDBOOK. The University of Iowa (UIHC), Department of Pathology. 28 May 2020. Archived from the original on 2008-10-11. Showing 95th percentiles. Epic Lab Code: LAB649.
  41. ^ Lam LL, Cameron PA, Schneider HG, Abramson MJ, Müller C, Krum H (December 2010). "Meta-analysis: effect of B-type natriuretic peptide testing on clinical outcomes in patients with acute dyspnea in the emergency setting". Annals of Internal Medicine. 153 (11): 728–35. doi:10.7326/0003-4819-153-11-201012070-00006. PMID 21135296. S2CID 27272593.
  42. ^ Bibbins-Domingo K, Gupta R, Na B, Wu AH, Schiller NB, Whooley MA (January 2007). "N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease". JAMA. 297 (2): 169–76. doi:10.1001/jama.297.2.169. PMC 2848442. PMID 17213400.
  43. ^ Fitzgerald RL, Cremo R, Gardetto N, Chiu A, Clopton P, Bhalla V, et al. (September 2005). "Effect of nesiritide in combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure". American Heart Journal. 150 (3): 471–7. doi:10.1016/j.ahj.2004.11.021. PMID 16169326.
  44. ^ Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW, et al. (February 2004). "Impact of obesity on plasma natriuretic peptide levels". Circulation. 109 (5): 594–600. CiteSeerX 10.1.1.541.9955. doi:10.1161/01.CIR.0000112582.16683.EA. PMID 14769680. S2CID 13454777.
  45. ^ O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, et al. (July 2011). "Effect of nesiritide in patients with acute decompensated heart failure" (PDF). The New England Journal of Medicine. 365 (1): 32–43. doi:10.1056/NEJMoa1100171. hdl:11379/60663. PMID 21732835.
  46. ^ McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. (September 2014). "Angiotensin-neprilysin inhibition versus enalapril in heart failure". The New England Journal of Medicine. 371 (11): 993–1004. doi:10.1056/NEJMoa1409077. hdl:10993/27659. PMID 25176015. S2CID 11383.
  47. ^ Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, et al. (February 2019). "Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure". The New England Journal of Medicine. 380 (6): 539–548. doi:10.1056/NEJMoa1812851. PMID 30415601.

Further reading

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attribution: copied from Brain natriuretic peptide version as of 13:57, 4 December 2019

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