Lab It Up: Elevated BNP

Elevated BNP

>100 pg/mL

A precursor of brain natriuretic peptide (BNP), pre-proBNP, is secreted from cardiac ventricular musculature in response to volume or pressure overload. BNP is thus used as a marker for heart failure.
In the emergency department, the serum BNP test helps to evaluate patients with acute undifferentiated dyspnea, assessing specifically for heart failure.
At BNP levels below the manufacturer-recommended cutoff for normal (<100 pg/mL), heart failure is very unlikely. In a 2015 systematic review and meta-analysis of BNP levels in acute care settings, the pooled test characteristics were [1]:
- Sensitivity 95% (95% CI 93–96%)
- Specificity 63% (95% CI 52-73%)
- Positive predictive value: 67% (95% CI 63-75%)
- Negative predictive value: 94% (95% CI 90-96%)
Slight BNP elevations (100-500 pg/mL) are in the “gray area” and can be challenging to interpret. Pooled test characteristics are as follows [1]:
- Sensitivity 85% (95% CI 81-88%)
- Specificity 86% (95% CI 79-91%)
- Positive likelihood ratio 85% (95% CI 78-90%)
- Negative likelihood ratio 82% (95% CI 82-89%)

Causes [2-4]

Heart failure

Can be acute or chronic

Right heart dysfunction from pulmonary disease

Pneumonia or other acute respiratory illness
Pulmonary embolism
Pulmonary hypertension
Chronic lung disease

Left ventricular dysfunction

Acute coronary syndrome
Valvular heart disease
Cardiac dysrhythmia
Congenital heart disease

Cardiac inflammatory process

Infectious endocarditis
Myocarditis
Pericarditis

Volume overload

Liver cirrhosis
Renal failure
High output state

Decreased BNP clearance

Older age
Acute or chronic renal disease

Other causes

Hyperthyroidism
Sepsis
Shock
Intracranial pathology

Special Populations

Pediatrics

Serum BNP levels can help screen for neonatal congenital heart disease and assess for pediatric heart disease [5]. The normal BNP cutoffs vary by age, highest in the first 3 days of age, presumably from decreased pulmonary vascular resistance, immature kidneys, and desired natriuresis. It then declines to remain at a low level from age 1 month to 12 years, as reported in this 2009 paper by Cantinotti et al. [6]:

Age	Median serum BNP value (pg/mL)	Range (pg/mL)
0-24 hour (1 day old)	224	41-837
25-48 hour (2 days old)	242	53-866
49-96 hour (3-4 days old)	152	23-862
97-192 hr (4-7 days old)	45	10-739
8-30 days	27	9-63
31 days to 1 year	19	1-53
1-12 years	14.5	1-46

Pregnancy

Serum BNP levels can be used to assess for heart failure in pregnancy. Be aware that while a level <100 pg/mL has excellent negative predictive value, the converse is not true. BNP levels can be slightly higher during pregnancy, especially in the immediate post-partum period. In a study of 773 normal early post-partum patients, 6.1% had levels ≥100 pg/mL and 1% had levels ≥200 pg/mL [7].

Key Insights

A falsely low BNP

A falsely normal BNP or unexpectedly mild elevation in BNP level can occur in the following settings:

Patient obesity [8]
Flash pulmonary edema (too early to detect significant BNP elevation)
Constrictive pericarditis or restrictive cardiomyopathy [9]

In-hospital prognostication

Admission BNP levels correlate with in-hospital mortality for patients with preserved or reduced systolic fraction in the 2007 ADHERE trial [10]:

BNP level (pg/mL)	In-hospital mortality
<430	1.9%
430-839	2.8%
840-1729	3.8%
≥1730	6.0%

Lab It Up Library

You order a battery of laboratory tests on your patient in the Emergency Department and few results are highlighted as abnormal in red. Why is it abnormal? Are you forgetting causes? The “Lab It Up” library helps Emergency Department clinicians to recall relevant differential diagnoses for abnormal laboratory results.

View the full Lab It Up Library list.

Originally published Feb 12, 2023 (updated February 13, 2023)

Lab It Up Library

View the full Lab It Up Library list.

Originally published Feb 12, 2023 (updated February 13, 2023)

References

Roberts E, Ludman AJ, Dworzynski K, et al. The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting. BMJ. 2015;350:h910. Published 2015 Mar 4. doi:10.1136/bmj.h910. PMID 25740799
Tsai SH, Lin YY, Chu SJ, Hsu CW, Cheng SM. Interpretation and use of natriuretic peptides in non-congestive heart failure settings. Yonsei Med J. 2010;51(2):151-163. doi:10.3349/ymj.2010.51.2.151. PMID 20191004
Fish-Trotter H, Ferguson JF, Patel N, et al. Inflammation and Circulating Natriuretic Peptide Levels. Circ Heart Fail. 2020;13(7):e006570. doi:10.1161/CIRCHEARTFAILURE.119.006570. PMID 32507024
Costello-Boerrigter LC, Boerrigter G, et al. Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction. J Am Coll Cardiol. 2006 Jan 17. 47(2):345-53. PMID 16412859
Neves AL, Henriques-Coelho T, Leite-Moreira A, Areias JC. The Utility of Brain Natriuretic Peptide in Pediatric Cardiology: A Review. Pediatr Crit Care Med. 2016;17(11):e529-e538. doi:10.1097/PCC.0000000000000966. PMID 27749513
Cantinotti M, Storti S, Parri MS, et al. Reference values for plasma B-type natriuretic peptide in the first days of life. Clin Chem 2009; 55:14381440. PMID 19478025
Sarma A, Aggarwal N, Briller J, et al. The Utilization and Interpretation of Cardiac Biomarkers During Pregnancy. JACC Adv. 2022 Aug, 1 (3) .
https://doi.org/10.1016/j.jacadv.2022.100064
Horwich TB, Hamilton MA, Fonarow GC. B-type natriuretic peptide levels in obese patients with advanced heart failure. J Am Coll Cardiol. 2006 Jan 3. 47(1):85-90. PMID 16386669
Babuin L, Alegria JR, Oh JK, Nishimura RA, Jaffe AS. Brain natriuretic peptide levels in constrictive pericarditis and restrictive cardiomyopathy. J Am Coll Cardiol. 2006 Apr 4. 47(7):1489-91. PMID 16580543
Fonarow GC, Peacock WF, Phillips CO, Givertz MM, Lopatin M; ADHERE Scientific Advisory Committee and Investigators. Admission B-type natriuretic peptide levels and in-hospital mortality in acute decompensated heart failure. J Am Coll Cardiol. 2007;49(19):1943-1950. doi:10.1016/j.jacc.2007.02.037. PMID 17498579