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Heart failure: elevated plasma B-type natriuretic peptide concentrations inhibit circulating neprilysin activity


A study sought to hypothesize that elevated B-type natriuretic peptide ( BNP ) could act as an endogenous neprilysin inhibitor.

A hallmark of acute decompensated heart failure ( ADHF ) is the overproduction of natriuretic peptides ( NPs ) by stretched cardiomyocytes. Various strategies have been developed to potentiate the beneficial effect of the natriuretic peptides, including the recent use of neprilysin angiotensin receptor inhibitors. Contrary to rodents, human BNP is poorly sensitive to neprilysin degradation while retaining affinity to neprilysin.

Researchers enrolled 638 patients presenting to the Emergency Department with acute dyspnea of which 468 had ADHF and 169 had dyspnea of noncardiac origin. 46 patients with stable chronic heart failure ( HF ) and 10 age-matched healthy subjects were also included.

Plasma samples were collected within 4 h after Emergency Department admission. BNP, neprilysin concentration and activity, and the neprilysin substrate substance P concentration were measured.

Researchers found that when plasma BNP rose above 916 pg/ml, neprilysin activity was markedly reduced ( p less than 0.0001 ) and stratified 95% of the population into 2 groups: BNP less than 916 pg/ml/neprilysin activity greater than or equal to 0.21 nmol/ml/min and BNP greater than or equal to 916 pg/ml/neprilysin activity more than 0.21 nmol/ml/min with very different prognoses.

In vitro, BNP was responsible for neprilysin inhibition. Neprilysin activity was inversely correlated with the concentration of substance P ( ρ = −0.80; p less than 0.0001 ).

In conclusion, besides being an effector of the cardiac response to cardiomyocyte stretching in ADHF, elevated plasma BNP is also an endogenous neprilysin inhibitor.
A biologically relevant BNP threshold discriminates 2 populations of HF patients with different vasoactive peptide profiles and outcome.
If confirmed, this may identify an important threshold for managing HF patients.

Perspectives

Immunoreactive BNP is a gold-standard biomarker in heart failure; a cutoff at 916 pg/ml discriminates patients with high and low neprilysin activity, hence potentially predicts responders to neprilysin inhibition. ( Xagena )

Nicolas Vodovar N et al, JCHF 2015;3:629-636

XagenaMedicine_2015



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