Alternate Circulating Pro-B-Type Natriuretic Peptide and B-Type Natriuretic Peptide Forms in the General Population
Carolyn S.P. Lam, MBBS, MRCP*, ,
John C. Burnett, Jr, MD*,
Lisa Costello-Boerrigter, MD, PhD*,
Richard J. Rodeheffer, MD, FACC* and
Margaret M. Redfield, MD, FACC*,1,*
* Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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Figure 1 ProBNP Processing
ProBNP is a 108-amino acid (aa) precursor protein which is cleaved by the endoprotease corin to form the bioactive 32 aa BNP peptide (referred to as BNP1-32 or as proBNP77-108) and the inert 76 aa N-terminal-proBNP peptide (proBNP1-76). Each fragment undergoes further N-terminal dipeptidase digestion, as might proBNP itself. BNP = B-type natriuretic peptide.
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Figure 2 Commercial BNP or NT-proBNP Assays
Commercial BNP or NT-proBNP assays utilize dual antibody systems which recognize 2 separate segments of BNP1-32 or of NT-proBNP1-76, respectively. (Left) The Roche NT-proBNP assay combines a capture antibody targeting proBNP aa 1-21 with a detection antibody recognizing proBNP aa 39-50. (Right) The Biosite Triage assay combines the monoclonal Scios 106.3 antibody, which binds somewhere in the proBNP aa 82-90 region, with the Biosite polyclonal antibody, which binds somewhere in the proBNP aa 79-108 region. Other abbreviations as in Figure 1.
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Figure 3 Biosite ProBNP3-108 and BNP3-32 Assays
(Left) The proBNP3-108 assay combines an antibody specific for the N-terminus aa 3 of proBNP with the Biosite polyclonal antibody used in the Triage assay. (Right) The BNP3-32 assay combines an antibody specific for the N-terminus aa 3 of BNP with the Biosite polyclonal antibody used in the Triage assay. Abbreviations as in Figure 1.
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Figure 4 Percentage of Subjects With Detectable Assay Results
Bars represent the percentage of subjects in each group (see text) with measured levels above the minimal detectable concentration of each assay. Chi-square p values for between-group comparisons are given for each assay. ALVD = asymptomatic left ventricular dysfunction; BNP = B-type natriuretic peptide; CV = cardiovascular; HF = heart failure; MDC = minimal detectable concentration; NT = N-terminal.
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Figure 5 Assay Results by Subject Group
Boxplots showing median, interquartile range, minimum, and maximum observed immunoreactivity in pmol/l by subject group (see text). For each assay, *represents p < 0.05 for comparison of mean values between that group and the previous group, adjusting for age, gender, creatinine, and body surface area. Abbreviations as in Figure 4.
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Figure 6 ROC Curves for Detection of ALVD and HF
(A) ROC curves for detection of ALVD using the different assays. (B) ROC curves for detection of HF using the different assays. AUC = area under the curve; other abbreviations as in Figure 4.
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