Brain natriuretic peptide (BNP), now known as B-type natriuretic peptide or Ventricular Natriuretic Peptide (still BNP), is a 32-amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells (cardiomyocytes). The release of BNP is modulated by calcium ions. BNP is named as such because it was originally identified in extracts of porcine brain, although in humans it is produced mainly in the cardiac ventricles.
BNP is secreted along with a 76-amino acid N-terminal fragment (NT-proBNP) that is biologically inactive. BNP binds to and activates the atrial natriuretic factor receptors NPRA, and to a lesser extent NPRB, in a fashion similar to atrial natriuretic peptide (ANP) but with 10-fold lower affinity. The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing.
The physiologic actions of BNP are similar to those of ANP and include decrease in systemicvascular resistance and central venous pressure as well as an increase in natriuresis. Thus, the net effect of BNP and ANP is a decrease in blood volume, which lowers systemic blood pressure and afterload, yielding an increase in cardiac output, partly due to a higher ejection fraction.
BNP is synthesized as a 134-amino acid preprohormone (preproBNP), encoded by the human gene NPPB. Removal of the 25-residue N-terminal signal peptide generates the prohormone, proBNP, which is stored intracellularly as an O-linked glycoprotein; proBNP is subsequently cleaved between arginine-102 and serine-103 by a specific convertase (probably furin or corin) into NT-proBNP and the biologically active 32-amino acid polypeptide BNP-32, which are secreted into the blood in equimolar amounts. Cleavage at other sites produces shorter BNP peptides with unknown biological activity. Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites.
The main clinical utility of either BNP or NT-proBNP is that a normal level rules out acute heart failure in the emergency setting. An elevated BNP or NT-proBNP should never be used to "rule in" acute or heart failure in the emergency setting due to lack of specificity[dubious– discuss].
Either BNP or NT-proBNP can also be used for screening and prognosis of heart failure.
Both are also typically increased in patients with left ventricular dysfunction, with or without symptoms (BNP accurately reflects current ventricular status, as its half-life is 20 minutes, as opposed to 1–2 hours for NT-proBNP).
BNP can be elevated in renal failure. BNP is cleared by binding to natriuretic peptide receptors (NPRs) and neutral endopeptidase (NEP). Less than 5% of BNP is cleared renally. NT-proBNP is the inactive molecule resulting from cleavage of the prohormone Pro-BNP and is reliant solely on the kidney for excretion. The achilles heel of the NT-proBNP molecule is the overlap in kidney disease in the heart failure patient population.
Some laboratories report in units ng per Litre (ng/L), which is equivalent to pg/ml
For patients with heart failure, BNP values will, in general, be above 100 pg/ml.
A more conservative interpretation of the BNP is that normal values are less than 50 pg/ml, in order to achieve adequate sensitivity.
There is a diagnostic 'gray area', often defined as between 100 and 500 pg/ml, for which the test is considered inconclusive, but, in general, levels above 500 pg/ml are considered to be positive. This so-called gray zone has been addressed in several studies, and using clinical history or other available simple tools can help make the diagnosis.
BNP may be a reliable predictor of cardiovascular mortality in diabetics.
BNP was found to have an important role in prognostication of heart surgery patients and in the emergency department. Bhalla et al. showed that combining BNP with other tools like ICG can improve early diagnosis of heart failure and advance prevention strategies. Utility of BNP has also been explored in various settings like preeclampsia, ICU and shock and ESRD.
The effect or race and gender on value of BNP and its utility in that context has been studied extensively.
NT-proBNP levels (in pg/mL) by NYHA functional class 
The BNP test is used as an aid in the diagnosis and assessment of severity of heart failure. A recent meta-analysis concerning effects of BNP testing on clinical outcomes of patients presenting to the emergency department with acute dyspnea revealed that BNP testing led to a decrease in admission rates and decrease in mean length of stay, although neither was statistically significant. Effects on all cause hospital mortality was inconclusive. The BNP test is also used for the risk stratification of patients with acute coronary syndromes.
When interpreting an elevated BNP level, it is useful to remember that values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients. Higher levels are seen in those with renal disease, in the absence of heart failure.
Recombinant BNP, nesiritide, is used to treat decompensated heart failure. However, a recent clinical trial failed to show a benefit of nesiritide in patients with acute decompensated heart failure, and the authors could not recommend its use.
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