Natriuretic peptides (NP)
NP release and actions
Natriuretic peptides (NPs) are secreted by the myocardium in response to stretch. In health, they are part of the homeostatic systems maintaining blood volume. They counter-act many of the pathophysiological processes of heart failure. There are four different natriuretic peptides; A-type natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and urodilatin.
Actions of NPs (figure 1):
- inhibition of the sympathetic nervous system
- inhibition of the renin–angiotensin–aldosterone system (RAAS).
Serum NP levels can be measured using immunoassay testing which is quick, easy and cheap. The major role for natriuretic peptide testing is in excluding the diagnosis of heart failure in a breathless patient: those patients with levels below defined cut-offs do not have heart failure, and an alternative diagnosis for the symptoms should be sought. Natriuretic peptide testing may prove to be useful for screening, and gives prognostic information about patients with heart failure.
NPs and diagnosis
The signs and symptoms of heart failure can be misinterpreted in the absence of further investigation. NPs can exclude heart failure as a cause of breathlessness in patients presenting either acutely or with a more gradual onset of symptoms.
Low serum NPs have a high negative predictive value and very high levels of NPs have a high positive predictive value for the diagnosis of heart failure. However, there are several non-cardiac causes for elevated levels that should be considered in the clinical context (table 2).
BNP and N-terminal peptide of prohormone brain natriuretic peptide (NTproBNP) are the most frequently measured NPs.
BNP is produced by cleavage of a precursor molecule, proBNP, into an inactive fragment (amino-terminal proBNP, NtproBNP, and BNP itself. Both can potentially be measured (as can many other elements of the natriuretic peptide system). The emergence of neprilysin inhibitors, which prevent the breakdown of BNP (thus increasing levels), means that NTproBNP may be the standard test in clinical practice in years to come.
NPs and prognosis
Serum NPs are, at present, the best single prognostic test for heart failure.
- NP concentrations predict outcome more accurately than LVEF or other neurohormones in patients with advanced heart failure
- high serum NP concentrations are associated with an increased risk of sudden death in patients with chronic heart failure
- high NP concentrations are associated with an increased risk of in-hospital mortality, regardless of ejection fraction
- high NP concentrations at discharge are associated with increased risk of re-admission or death for at least six months post-admission
- an increase in NP concentration during admission is associated with increased risk of adverse events whereas a decrease in serum NP levels are associated with lower risk.