N-terminal prohormone of brain natriuretic peptide

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natriuretic peptide B
Identifiers
SymbolNPPB
NCBI gene4879
HGNC7940
OMIM600295
RefSeqNM_002521
UniProtP16860
Other data
LocusChr. 1 p36.2
Search for
StructuresSwiss-model
DomainsInterPro

The N-terminal prohormone of brain natriuretic peptide (NT-proBNP or BNPT) is a prohormone with a 76 amino acid N-terminal inactive protein that is cleaved from the molecule to release brain natriuretic peptide 32 (BNP, also known as B-type natriuretic peptide).

Both BNP and NT-proBNP levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure, as both markers are typically higher in patients with worse outcome.[1] The plasma concentrations of both BNP and NT-proBNP are also typically increased in patients with asymptomatic or symptomatic left ventricular dysfunction and is associated with coronary artery disease, myocardial ischemia, and severity of aortic valve stenosis.[2][3][4][5][6][7]

Blood levels

Upper limit (95th percentile) of blood ranges
for NT-proBNP in healthy people
[8]
Sex Age Limit
in pg/mL
Male 19-44 yrs 93
45-54 yrs 138
55-64 yrs 177
65-74 yrs 229
> 75 yrs 852
Females 19-44 yrs 178
45-54 yrs 192
55-64 yrs 226
65-74 yrs 353
> 75 yrs 624
Interpretation Age Range
Congestive heart failure likely <75 years > 125 pg/mL[9]
>75 years >450pg/mL[9]

There is no level of BNP that perfectly separates patients with and without heart failure.[10]

In screening for congenital heart disease in pediatric patients, an NT-proBNP cut-off value of 91 pg/mL could differentiate an acyanotic heart disease (ACNHD) patient from a healthy patient with a sensitivity of 84% and specificity of 42%.[11] On the other hand, an NT-proBNP cut-off value of 318 pg/mL is more appropriate in differing patients with congenital nonspherocytic hemolytic disease (CNHD) from healthy patients, with 94% sensitivity and 97% specificity.[11] An NT-proBNP value of 408 pg/mL has been estimated to be 83% sensitive and 57% specific in differentiating patients with ACNHD from patients with CNHD.[11] In patients with non-severe asymptomatic aortic valve stenosis, increased age- and sex adjusted NT-proBNP levels alone and combined with a 50% or greater increase from baseline had been found associated with increased event rates of aortic valve stenosis related events (cardiovascular death, hospitalization with heart failure due to progression of aortic valve stenosis, or aortic valve replacement surgery).[12] In severe aortic valve stenosis, NT-proBNP provide important prognostic information beyond clinical and echocardiographic evaluation.[13]

Test usage in a clinical setting

Canada

While discussed in Canadian medical journals in the mid to late 2000s,[14] the test is not widely used. It was only approved for use in Alberta in February 2012.[15]

Test usage in the life insurance industry

The test has been widely used in the life insurance industry to screen applicants as part of the routine requirements when applying for a life insurance policy. It is also inexpensive and can be measured from blood samples routinely drawn as part of the application process. The test can be used to evaluate for a number of health conditions.[7][16][17]

See also

References

  1. ^ 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.
  2. ^ 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): 518–523. doi:10.1016/j.ahj.2004.03.014. PMID 15389242.
  3. ^ Nakamura T, Sakamoto K, Yamano T, Kikkawa M, Zen K, Hikosaka T, et al. (May 2002). "Increased plasma brain natriuretic peptide level as a guide for silent myocardial ischemia in patients with non-obstructive hypertrophic cardiomyopathy". Journal of the American College of Cardiology. 39 (10): 1657–1663. doi:10.1016/s0735-1097(02)01813-2. PMID 12020494.
  4. ^ Talwar S, Squire IB, Downie PF, Davies JE, Ng LL (October 2000). "Plasma N terminal pro-brain natriuretic peptide and cardiotrophin 1 are raised in unstable angina". Heart. 84 (4): 421–424. doi:10.1136/heart.84.4.421. PMC 1729429. PMID 10995414.
  5. ^ Kim H, Yang DH, Park Y, Han J, Lee H, Kang H, et al. (November 2006). "Incremental prognostic value of C-reactive protein and N-terminal proB-type natriuretic peptide in acute coronary syndrome". Circulation Journal. 70 (11): 1379–1384. doi:10.1253/circj.70.1379. PMID 17062957.
  6. ^ Ruwald MH, Goetze JP, Bech J, Nielsen OW, Madsen BK, Nielsen LB, et al. (January 2014). "NT-ProBNP independently predicts long-term mortality in patients admitted for coronary angiography". Angiology. 65 (1): 31–36. doi:10.1177/0003319712462758. PMID 23070682. S2CID 33475819.
  7. ^ a b Hadziselimovic E, Greve AM, Sajadieh A, Olsen MH, Kesäniemi YA, Nienaber CA, et al. (April 2022). "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. PMC 8851368. PMID 35171199.
  8. ^ "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.
  9. ^ a b Lee MA (2009). Basic Skills in Interpreting Laboratory Data. Amer Soc of Health System. p. 220. ISBN 978-1-58528-180-0.
  10. ^ 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): 161–167. doi:10.1056/NEJMoa020233. PMID 12124404.
  11. ^ a b c Moses EJ, Mokhtar SA, Hamzah A, Abdullah BS, Yusoff NM (2011). "Usefulness of N-Terminal-Pro-B-Type Natriuretic Peptide as a Screening Tool for Identifying Pediatric Patients With Congenital Heart Disease". Laboratory Medicine. 42 (2): 75–80. doi:10.1309/LMW0U87COTHXGELF.
  12. ^ Hadziselimovic E, Greve AM, Sajadieh A, Olsen MH, Kesäniemi YA, Nienaber CA, et al. (April 2022). "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. PMC 8851368. PMID 35171199.
  13. ^ Bergler-Klein J, Klaar U, Heger M, Rosenhek R, Mundigler G, Gabriel H, Binder T, Pacher R, Maurer G, Baumgartner H (2004-05-18). "Natriuretic Peptides Predict Symptom-Free Survival and Postoperative Outcome in Severe Aortic Stenosis". Circulation. 109 (19): 2302–2308. doi:10.1161/01.CIR.0000126825.50903.18. ISSN 0009-7322. PMID 15117847.
  14. ^ Murray H, Cload B, Collier CP, Sivilotti ML (July 2006). "Potential impact of N-terminal pro-BNP testing on the emergency department evaluation of acute dyspnea". CJEM. 8 (4): 251–258. doi:10.1017/s1481803500013798. PMID 17324304.
  15. ^ "B-type Natriuretic Peptide (BNP) & NT-proBNP Test Implementation". Alberta Health Services. Archived from the original on 22 April 2015. Retrieved 3 January 2013.
  16. ^ George H (2010). "NT-proBNP The Finest Cardiovascular Screening and Reflexive Test In the History of Life Underwriting" (PDF). Insureintell. Retrieved 11 July 2016.
  17. ^ Clark M, Kaufman V, Fulks M, Dolan VF, Stout RL (2014). "NT-proBNP as a predictor of all-cause mortality in a population of insurance applicants". Journal of Insurance Medicine. 44 (1): 7–16. PMID 25004594.

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