Synonym: B-type natriuretic peptide
Brain natriuretic peptide (BNP) levels increase markedly in left ventricular dysfunction and the level in heart failure correlates with symptom severity. BNP can therefore be an important clinical marker for the diagnosis of heart failure in patients with unexplained dyspnoea. Other clinical applications, such as screening for asymptomatic ventricular dysfunction, establishing the prognosis or guiding the titration of drug therapy and prediction of future cardiovascular events, are under investigation but have not yet been sufficiently validated for widespread clinical use.
BNP is a biologically active peptide of 32 amino acids and has vasodilator and natriuretic properties. BNP is cleaved from the 108-amino acid pro-brain natriuretic peptide released from the cardiac ventricles in response to stretching of the chamber. The second remnant after cleavage, N-terminal pro-brain natriuretic peptide (NT-proBNP), is a 76-amino acid peptide with no known biological function which circulates at higher concentrations than BNP and may represent cardiac status over longer periods.
The release of BNP appears to be in direct proportion to ventricular volume expansion and pressure overload. BNP increases with right or left systolic or diastolic heart failure. It is an independent predictor of high left ventricular end-diastolic pressure. BNP levels decrease after effective treatment of heart failure.
Although testing for BNP provides a useful adjunct to routine assessment for differentiating acute heart failure from other causes of breathlessness, other factors such as comorbid illnesses, age, chronic kidney disease and body mass may affect BNP levels in ways that can obscure the diagnosis of heart failure, particularly when this marker is used in isolation. Therefore, it is essential that BNP be used to aid diagnosis in addition to the patient's history, clinical signs and other investigations. The role of BNP in heart failure and whether it is a target to treat or risk identifier remain contentious.
There is currently no definite evidence of a clinical advantage between using either BNP assay or NT-proBNP assay.
- The most commonly used decision threshold for BNP is 100 pg/ml.
- BNP levels of more than 100 pg/ml have a greater than 95% specificity and greater than 98% sensitivity when comparing patients without congestive heart failure (CHF) to all patients with CHF.[2, 5]
- Even BNP levels of more than 80 pg/ml have a greater than 93% specificity and 98% sensitivity in the diagnosis of heart failure.
- BNP levels rise with age. Mean BNP levels are:
- 26.2 pg/ml in those aged 55-64 years.
- 31.0 pg/ml in those aged 65-74 years.
- 63.7 pg/ml in those aged 75 years and older.
- Women without CHF tend to have higher BNP levels than males of the same age.
Patients should have had an ECG, CXR, FBC, renal function and electrolytes tests, LFTs, lipid profile, TFTs and any other investigation relevant to the clinical presentation.
Potential causes of elevated brain natriuretic peptide levels
- Heart failure.
- Diastolic dysfunction.
- Acute coronary syndromes.
- Hypertension with left ventricular hypertrophy.
- Valvular heart disease (aortic stenosis, mitral valve regurgitation).
- Atrial fibrillation.
- Acute pulmonary embolism.
- Pulmonary hypertension (primary or secondary).
- Sepsis (possibly due to tissue hypoxia or secondary myocardial depression).
- Chronic obstructive pulmonary disease with cor pulmonale or respiratory failure.
- Acute or chronic kidney injury.
BNP levels may be lower than expected when heart failure is secondary to causes proximal to the left ventricle - eg, acute mitral regurgitation, mitral stenosis or atrial myxoma.
Potential use of brain natriuretic peptide measurement
Assay of BNP is a potential aid in the diagnosis of heart failure. BNP testing allows a rapid assessment for defining those patients warranting an echocardiogram and also has the potential to enable rapid changes in therapy for those already receiving treatment for heart failure.
- BNP testing is effective in screening for left ventricular systolic dysfunction and reduces the number of patients requiring an echocardiogram.[6, 7]
- BNP levels correlate closely with the New York Heart Association (NYHA) Classification of Heart Failure as well as the Goldman Specific Activity Scale of Heart Failure.
- Normal concentrations virtually exclude the diagnosis of heart failure, and very high levels effectively diagnose the condition; intermediate values require further evaluation.
- Assay of BNP has potential as part of a diagnostic triage in patients presenting with symptoms suggestive of heart failure or in screening populations at high risk.
- In several pilot studies, BNP levels had a strong correlation with the severity of illness and were very reliable in differentiating heart failure from pulmonary disease.
- A pilot study has reviewed the role of finger prick testing for BNP at home and its usefulness in detecting decompensation. They found that BNP changes did help determine the risk of decompensation and it should complement other clinical markers of decompensation.
In a pilot study, BNP levels correlated highly with clinical outcomes:
- Patients with decreased BNP levels during their hospital stay, along with decreases in NYHA classification, had good outcomes.
- Patients whose hospital stay ended in death or readmission within 30 days of discharge had only minimal decreases of BNP levels or rising levels of BNP despite improvement or no change in their NYHA classification.
- The last measured BNP level was the single most reliable variable in predicting short-term outcomes in patients with heart failure.
Other potential clinical applications
- Raised plasma natriuretic peptide levels have been shown to predict the risk of death and cardiovascular events in people without heart failure after adjustment for traditional risk factors. Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure.
- Natriuretic peptides may help in identifying people at risk of stroke and atrial fibrillation.
- Admission BNP is an independent and powerful marker of early and late cardiac mortality in patients with acute chest pain without ST-segment elevation.
- Role in predicting stroke mortality.
Further reading and references
Chronic heart failure: Management of chronic heart failure in adults in primary and secondary care; NICE Clinical Guideline (August 2010)
Heart failure - chronic; NICE CKS, November 2010 (UK access only)
Ray SG; Natriuretic peptides in heart valve disease. Heart. 2006 Sep92(9):1194-7. Epub 2005 Oct 26.
Jankowski M; B-type natriuretic peptide for diagnosis and therapy. Recent Pat Cardiovasc Drug Discov. 2008 Jun3(2):77-83.
Hobbs FD, Davis RC, Roalfe AK, et al; Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosis of heart failure: cohort study in representative and high risk community populations. BMJ. 2002 Jun 22324(7352):1498.
Desai AS; Are serial BNP measurements useful in heart failure management? Serial natriuretic peptide measurements are not useful in heart failure management: the art of medicine remains long. Circulation. 2013 Jan 29127(4):509-16
Felker GM, Petersen JW, Mark DB; Natriuretic peptides in the diagnosis and management of heart failure. CMAJ. 2006 Sep 12175(6):611-7.
Kelder JC, Cowie MR, McDonagh TA, et al; Quantifying the added value of BNP in suspected heart failure in general practice: an individual patient data meta-analysis. Heart. 2011 Jun97(12):959-63. doi: 10.1136/hrt.2010.220426. Epub 2011 Apr 8.
Nielsen OW, McDonagh TA, Robb SD, et al; Retrospective analysis of the cost-effectiveness of using plasma brain natriuretic peptide in screening for left ventricular systolic dysfunction in the general population. J Am Coll Cardiol. 2003 Jan 141(1):113-20.
Sim V, Hampton D, Phillips C, et al; The use of brain natriuretic peptide as a screening test for left ventricular Fam Pract. 2003 Oct20(5):570-4.
Maisel A, Barnard D, Jaski B, et al; Primary results of the HABIT Trial (heart failure assessment with BNP in the home). J Am Coll Cardiol. 2013 Apr 2361(16):1726-35. doi: 10.1016/j.jacc.2013.01.052. Epub 2013 Mar 26.
Wang TJ, Larson MG, Levy D, et al; Plasma natriuretic peptide levels and the risk of cardiovascular events and N Engl J Med. 2004 Feb 12350(7):655-63.
Kurl S, Ala-Kopsala M, Ruskoaho H, et al; Plasma N-terminal fragments of natriuretic peptides predict the risk of stroke Heart. 2009 Jul95(13):1067-71. Epub 2009 Mar 24.
Bassan R, Tura BR, Maisel AS; B-type natriuretic peptide: a strong predictor of early and late mortality in patients with acute chest pain without ST-segment elevation in the emergency department. Coron Artery Dis. 2009 Mar20(2):143-9.
Jickling GC, Foerch C; Predicting stroke mortality: BNP could it be? Neurology. 2013 Dec 381(23):1970-1. doi: 10.1212/01.wnl.0000436949.75473.79. Epub 2013 Nov 1.