Comparison of Mass Spectrometry and Clinical Assay Measurements of Circulating Fragments of B-Type Natriuretic Peptide in Patients With Chronic Heart Failure

Miller, Wayne L.; Phelps, Mary; Wood, Christina M.; Schellenberger, Ute; Le, Anh‐Tu; Périchon, Régis; Jaffe, Allan S.

doi:10.1161/circheartfailure.110.960260

Cited by 107 publications

(100 citation statements)

References 22 publications

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“…NT-proBNP and degradation products have a half life of several hours, and plasma BNP concentrations measured in patients with heart failure correlate best with (biologically inactive) degradation products than with the functional BNP-32 (=BNP (1-32)) [30]. Nevertheless, chronic over-secretion of BNP (including active BNP) in chronic heart failure is indisputable.…”

Section: Discussionmentioning

confidence: 99%

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men

et al. 2011

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Aims/hypothesis B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism. Methods Ten healthy volunteers (25±1 years; BMI 23± 1 kg/m 2 ; fasting glucose 4.6±0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg −1 min −1 BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured.Results Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13±1% body weight vs 11±1%, p<0.002), leading to an overall reduction in glucose concentration (p<0.001), particularly during the initial 20 min of the test (p=0.001), accompanied by a reduction in the initial C-peptide levels (1.42± 0.13 vs 1.62±0.10 nmol/l, p=0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects. Conclusions/interpretation Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues. Trial registration: ClinicalTrials.gov: NCT01324739 Funding: The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

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Section: Discussionmentioning

confidence: 99%

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men

et al. 2011

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“…Although initially it was thought that there were only 2 circulating fragments of BNP, BNP 1-32 and NTproBNP 1-76, contemporary data have challenged this concept recently (23 ). Mass spectrometry analyses showed only minute amounts of circulating BNP 1-32.…”

Section: Degradation Fragments Of Bnp In Circulationmentioning

confidence: 99%

“…Another protease, peptidyl arginine aldehyde protease, can also degrade BNP, and meprin was shown to lyse BNP in animal models but not in humans (26 ). Due to BNP instability in EDTA plasma even at low temperatures, protease inhibitors in high concentrations should always be used (23 ).…”

Section: Degradation Fragments Of Bnp In Circulationmentioning

confidence: 99%

Natriuretic Peptides and Analytical Barriers

Vasile

Jaffe

2017

Clinical Chemistry

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BACKGROUND:The natriuretic peptide system is an endocrine, autocrine and paracrine system that plays an important role in the maintenance of cardiovascular homeostasis. Biomarkers based on these peptides are important diagnostic and prognostic tools for myocardial function.CONTENT: Although natriuretic peptides were discovered more than 2 decades ago, their intricate and complex biology is associated with important questions not yet elucidated. The diversity of circulating forms of natriuretic peptides, the distinct expression of these forms in particular patients, and the heterogeneity of heart failure forms, along with specific assay-related and preanalytic issues, cause assays to be poorly harmonized.

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“…As a result, NT-proBNP assay is not a reliable index of the biological (natriuretic) activity of cardiac endocrine system in severe HF because the concentration of less active peptides in patients with severe HF (such as NT-proBNP and proBNP) is greatly higher than that of the active peptide BNP (Figure 1) [1,[29][30][31][32][33]. Moreover, a recent study [34] suggested that the commercial immunoassays, commonly used for NTproBNP assay, employ non-glycosylated calibrator materials and mostly antibodies directed against epitopes with potential O-glycosylation site occupancy.…”

Section: Groupmentioning

confidence: 99%

“…In addition to the peptide hormone BNP and the inactive peptide NT-proBNP, a huge numbers of other circulating peptides derived from the pro-hormone proBNP can be identified by chromatographic procedures in human plasma, including the intact and glycosylated forms of proBNP itself [29][30][31][32][33]38] (Figure 2). Furthermore, the active hormone BNP may be produced even in vivo from the circulating intact precursor proBNP through enzymatic cleavage by some plasma proteases (such as corin) [35,36,39] (Figure 2).…”

Section: Quality Specifications For An Accurate Bnp Assaymentioning

confidence: 99%

New issues on measurement of B-type natriuretic peptides

Clerico

Zaninotto

Passino

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:The measurement of the active hormone of B-type natriuretic peptide (BNP) system actually has several analytical limitations and difficulties in clinical interpretations compared to that of inactive peptide N-terminal proBNP (NT-proBNP) because of the different biochemical and pathophysiological characteristics of two peptides and quality specifications of commercial immunoassay methods used for their measurement. Because of the better analytical characteristics of NT-proBNP immunoassays and the easier pathophysiological and clinical interpretations of variations of NT-proBNP levels in patients with heart failure (HF), some authors claimed to measure the inactive peptide NT-proBNP instead of the active hormone BNP for management of HF patients. The measurement of the active peptide hormone BNP gives different, but complementary, pathophysiological and clinical information compared to inactive NT-proBNP. In particular, the setup of new more sensitive and specific assays for the biologically active peptide BNP 1-32 should give better accurate information on circulating natriuretic activity. In conclusion, at present time, clinicians should accurately consider both the clinical setting of patients and the analytical characteristics of BNP and NT-proBNP immunoassays in order to correctly interpret the variations of natriuretic peptides measured by commercially available laboratory methods, especially in patients treated with the new drug class of angiotensin receptor-neprilysin inhibitors.

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Comparison of Mass Spectrometry and Clinical Assay Measurements of Circulating Fragments of B-Type Natriuretic Peptide in Patients With Chronic Heart Failure

Cited by 107 publications

References 22 publications

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men

Natriuretic Peptides and Analytical Barriers

New issues on measurement of B-type natriuretic peptides

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