NT-ProBNP Levels in Saliva and Its Clinical Relevance to Heart Failure

Foo, Jared Yong Yang; Wan, Yunxia; Kostner, Karam; Arivalagan, A.; Atherton, J.; Cooper-White, Justin J.; Dimeski, Goce; Punyadeera, Chamindie

doi:10.1371/journal.pone.0048452

Cited by 52 publications

(65 citation statements)

References 34 publications

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“…Therefore, if researchers use saliva to measure BNP and IL-10, they can expect that salivary results will be lower than serum results and that salivary values may underestimate high serum values. Foo et al (2012) reported that salivary NT-proBNP was 100% specific inidentifying patients with HF in comparison to healthy controls. Our study differed from Foo's in that we did not have healthy controls in our study, we measured BNP rather than NT-proBNP, and we used the Bland-Altman test in addition to correlation testing.…”

Section: Discussionmentioning

confidence: 99%

Salivary Biomarkers, Oral Inflammation, and Functional Status in Patients With Heart Failure

Dekker

Lennie

Moser

et al. 2016

Biological Research For Nursing

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Aims: To describe correlations and agreement between salivary and serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin (IL)-6, and IL-10 and determine which biomarkers predict worse functional class in patients with heart failure (HF). Methods: Serum and saliva were collected from 75 hospitalized patients with HF (57 + 12 years, 43% female, New York Heart Association [NYHA] Classes I [4%], II [43%], and III [53%]). Oral inflammation was rated as good, fair, or poor. Spearman's r and Bland-Altman were used to determine correlations and agreement of the salivary and serum forms of each biomarker. Logistic regressions were used to determine which biomarkers predicted worse NYHA functional class, controlling for depression, body mass index, smoking, and oral inflammation. Results: Median biomarker concentrations were as follows: BNP (serum 361 pg/ml, saliva 9 pg/ml), CRP (serum 13 ng/ml, saliva 25.6 ng/ml), IL-6 (serum 19.3 pg/ml, saliva 10.5 pg/ml), and IL-10 (serum 64.1 pg/ml, saliva 4.7 pg/ml). There was a moderate-to-strong correlation for serum-salivary CRP, weak correlation for serum-salivary IL-6, and no correlations for serum-salivary BNP and IL-10. The Bland-Altman test showed good salivaryserum agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. Visible oral inflammation was the only predictor of worse NYHA class.

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Section: Discussionmentioning

confidence: 99%

Salivary Biomarkers, Oral Inflammation, and Functional Status in Patients With Heart Failure

Dekker

Lennie

Moser

et al. 2016

Biological Research For Nursing

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“…Therefore, monoclonal antibodies that target the nonglycosylated sites between NTproBNP 28 -45 [i.e., NT-proBNP 30 -35 (Glu-Leu-GlnVal-Glu-Gln motif)] are likely to exclude the effects of O-glycosylation on the measurement of plasma NTproBNP. This, together with monoclonal antibodies targeting NT-proBNP [13][14][15][16][17][18][19][20] , is likely to provide a more standardized measurement of the plasma NT-proBNP for future "sandwich" immunoassays. Our data indicated that although immunoreactive NT-proBNP was present in human plasma as multiple fragments of the full-length NT-proBNP molecule, specific epitopes of the peptide appear to be more abundant, providing ideal targets for developing the next generation diagnostic assays for clinical use.…”

Section: Discussionmentioning

confidence: 99%

“…The 6 NT-proBNP immunoassays are named according to the first amino acid that the capture antibody binds to on the NT-proBNP molecule and the last amino acid that the detection antibody binds to on the NT-proBNP molecule of 1-76 amino acids: NT-proBNP 1-20 (5B6 1-12 and 13G12 [13][14][15][16][17][18][19][20] ); NT-proBNP (18H5 [13][14][15][16][17][18][19][20] and 11D1 28 -45 ); NTproBNP (5B6 [1][2][3][4][5][6][7][8][9][10][11][12] and 11D1 28 -45 ); NT-proBNP 28 -76 (11D1 28 -45 and 28F8 67-76 ); NT-proBNP (18H5 [13][14][15][16][17][18][19][20] and 28F8 67-76 ); NTproBNP 1-76 (5B6 [1][2][3][4][5][6][7][8][9][10][11][12] and 28F8 67-76 ). Each NTpr...…”

Section: Plasma Nt-probnp Alphalisa Immunoassaysmentioning

confidence: 99%

“…The NTproBNP standards were prepared using pooled plasma collected from healthy volunteers (n ϭ 10) and mixing it with the High Block immunoassay buffer in a ratio of 50%:50%. This enabled us to overcome the matrix (A), The 6 immunoassays use diagnostic-grade monoclonal antibodies to detect NT-proBNP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] , NT-proBNP , NT-proBNP , NT-proBNP 28 -76 , NT-proBNP , and NT-proBNP . N-and C-terminal proteolytic sites detected by our MS analysis are shown with red vertical lines.…”

Section: Plasma Nt-probnp Alphalisa Immunoassaysmentioning

confidence: 99%

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Circulating Fragments of N-Terminal Pro–B-Type Natriuretic Peptides in Plasma of Heart Failure Patients

Foo

Wan

Schulz³

et al. 2013

Clinical Chemistry

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BACKGROUND The use of nonstandardized N-terminal pro–B-type natriuretic peptide (NT-proBNP) assays can contribute to the misdiagnosis of heart failure (HF). Moreover, there is yet to be established a common consensus regarding the circulating forms of NT-proBNP being used in current assays. We aimed to characterize and quantify the various forms of NT-proBNP in the circulation of HF patients. METHODS Plasma samples were collected from HF patients (n = 20) at rest and stored at −80 °C. NT-proBNP was enriched from HF patient plasma by use of immunoprecipitation followed by mass spectrometric analysis. Customized homogeneous sandwich AlphaLISA® immunoassays were developed and validated to quantify 6 fragments of NT-proBNP. RESULTS Mass spectrometry identified the presence of several N- and C-terminally processed forms of circulating NT-proBNP, with physiological proteolysis between Pro2-Leu3, Leu3-Gly4, Pro6-Gly7, and Pro75-Arg76. Consistent with this result, AlphaLISA immunoassays demonstrated that antibodies targeting the extreme N or C termini measured a low apparent concentration of circulating NT-proBNP. The apparent circulating NT-proBNP concentration was increased with antibodies targeting nonglycosylated and nonterminal epitopes (P < 0.05). CONCLUSIONS In plasma collected from HF patients, immunoreactive NT-proBNP was present as multiple N- and C-terminally truncated fragments of the full length NT-proBNP molecule. Immunodetection of NT-proBNP was significantly improved with the use of antibodies that did not target these terminal regions. These findings support the development of a next generation NT-proBNP assay targeting nonterminal epitopes as well as avoiding the central glycosylated region of this molecule.

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“…In this study, saliva samples were collected from healthy controls (n = 40) without underlying heart conditions, and from HF patients (n = 45). They demonstrated that the salivary NT-proBNP immunoassay has a clinical sensitivity of 82.2% and specificity of 100%, PPV of 100%, and NPV of 83.3%, with an overall diagnostic accuracy of 90.6% [11]. Another study revealed that higher daily salivary alpha-amylase activity output correlated with increasing levels of NT-proBNP.…”

Section: Discussionmentioning

confidence: 98%

Salivary B-type natriuretic peptide: a new method for heart failure diagnosis and follow-up

2017

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A b s t r a c tBackground: Frequent hospital admissions and reduced quality of life are the main complications of heart failure (HF). Plasma B-type natriuretic peptide (BNP) levels have been considered as a cost-effective method of screening for left ventricular dysfunction. Studies regarding BNP-guided therapy revealed reduction in death or hospital stay for HF. Aim:As saliva has fewer limitations than blood in regard to sampling, the aim of the present study was to test if salivary BNP concentration might be a new biomarker in patients with chronic HF.Methods: This pilot study involved 35 admitted patients with decompensated HF diagnosis and 35 HF patients who had come for a check-up at the Department of Cardiology. The control group consisted of 25 people with no history of cardiac events. Saliva and plasma samples of all the participants were collected.Results: Mean plasma NT-proBNP was found at higher levels in admitted HF patients compared to outpatient HF (9.37 vs. 6.62 pg/mL, p < 0.001) and control groups (9.37 vs. 4.69 pg/mL, p < 0.001). Also, mean salivary BNP levels were higher in admitted patients with HF (6.50 ng/L, p < 0.001); and outpatient HF group (5.87 ng/L, p = 0.02) compared to the control group (5.64 ng/L). Conclusions:Our study demonstrated that BNP could be detected in saliva and that the level is higher in HF patients, especially symptomatic ones. This means that salivary BNP may be useful in the diagnosis and follow-up for patients with HF, especially in emergency settings.

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NT-ProBNP Levels in Saliva and Its Clinical Relevance to Heart Failure

Cited by 52 publications

References 34 publications

Salivary Biomarkers, Oral Inflammation, and Functional Status in Patients With Heart Failure

Salivary Biomarkers, Oral Inflammation, and Functional Status in Patients With Heart Failure

Circulating Fragments of N-Terminal Pro–B-Type Natriuretic Peptides in Plasma of Heart Failure Patients

Salivary B-type natriuretic peptide: a new method for heart failure diagnosis and follow-up

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