Brain natriuretic peptide

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.¹

What is Brain natriuretic peptide?

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.²

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.

Until recently, BNP measurement was controversial as there was no clear evidence of the value of treating BNP levels, independent of symptoms.³ Recent studies have confirmed that treating BNP levels reduces morbidity and mortality.⁴The STRONG-HF study was stopped early due to the benefits seen in rapid up-titration of heart failure medication guided by BNP measurement.

BNP has been shown to be the single most accurate predictor of the absence of heart failure if the levels are below 100 nanomoles per litre.⁴

Measurement of brain natriuretic peptide

BNP is mainly used in the assessment of patients with possible heart failure. The National Institute for Health and Care Excellence (NICE) recommends:⁵

• Measure N-terminal pro-B-type natriuretic peptide (NT-proBNP) in people with suspected heart failure.

• Because very high levels of NT-proBNP carry a poor prognosis, refer people with suspected heart failure and an NT-proBNP level above 2000 ng/litre (236 pmol/litre) urgently, to have specialist assessment and transthoracic echocardiography within two weeks.

• Refer people with suspected heart failure and an NT-proBNP level between 400 and 2000 ng/litre (47 to 236 pmol/litre) to have specialist assessment and transthoracic echocardiography within six weeks.

• An NT-proBNP level less than 400 ng/litre (47 pmol/litre) in an untreated person makes a diagnosis of heart failure less likely. The level of serum natriuretic peptide does not differentiate between heart failure with reduced ejection fraction and heart failure with preserved ejection fraction.

• Review alternative causes for symptoms of heart failure in people with NT-proBNP levels below 400 ng/litre. If there is still concern that the symptoms might be related to heart failure, discuss with a heart failure specialist.

Potential causes of abnormal brain natriuretic peptide levels⁵

High levels of serum natriuretic peptides can be associated with:

• Age over 70 years.

• Heart failure

• Left ventricular hypertrophy.

• Ischaemia.

• Tachycardia.

• Right ventricular overload.

• Hypoxaemia (including pulmonary embolism).

• Renal dysfunction (eGFR less than 60 ml/minute/1.73 m2).

• Sepsis.

• Chronic obstructive pulmonary disease.

• Diabetes.

• Cirrhosis of the liver.

• Inflammation.⁶⁷

Reduced levels of serum natriuretic peptides can occur with:

• Obesity.

• African or African-Caribbean family origin.

• Treatment with diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, angiotensin II receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs).