BNP VS NT-proBNP

BENEFITS OF BNP TESTING PROOF SOURCES

BNP is an active hormone which is released to decrease fluid and PreproBNP (134aa)
Molecules
Different

volume overload. NT-proBNP is a bi-product and does not assist in

decreasing fluid overload. proBNP (108aa) signal peptide (26aa)
Secretion
BNP Expert Consensus Panel 2004 states, “NT-proBNP and bioactive MYOCYTE
BNP are NOT interchangeable.”1 NT-proBNP (1-76) BNP (77-108)

20 minutes half-life for BNP vs. 120 minutes for NT-proBNP.

BNP Has a Shorter Half-Life

BNP’s ideal half-life allows clinicians to assess a patient’s current

disease severity.
BNP’s optimal half-life allows clinicians to quickly measure response
to therapy. Adapted from
Mair et al.2

BNP levels reflect current ventricular status and response to therapy.

BNP concentration significantly decreases within 60 minutes,
whereas NT-proBNP shows a significant decrease not earlier than 24
hours after levosimedan infusion.3
Adapted from
Gegenhuber et al.3

BNP is actively cleared by neutral endopeptidase, natriuretic peptides Comparison of the Efficiency of the Emergency Physician, the
receptors and by the kidney. Although BNP is somewhat elevated in N-Terminal ProBNP and B-Type Natriuretic Peptide Concentrations
renal insufficiency patients, its diagnostic utility is unaffected.5 in the Diagnosis of Cardiogenic Pulmonary Edema
NT-proBNP is cleared solely by the kidney and is markedly elevated
in patients with mild renal insufficiency resulting in severely Emergency
proBNP BNP
Diagnostic Physician
compromised diagnostic utility.4,6
Performance Value (95% Confidence)
29% of CHF patients have renal disease.7
Sensitivity 0.73 (0.63-0.81) 0.75 (0.65-0.83) 0.73 (0.65-0.81)
Sykes et al. showed that 99% of patient samples with a creatinine
Specificity 0.79 (0.71-0.85) 0.76 (0.67-0.83) 0.91 (0.85-0.95)*†
value above 1.5 mg/dL had an elevated NT-proBNP concentration
regardless of cardiac status.6 Positive Predictive Value 0.73 (0.63-0.81) 0.71 (0.61-0.79) 0.86 (0.77-0.92)*†
Negative Predicitive Value 0.79 (0.71-0.85) 0.80 (0.71-0.86) 0.81 (0.74-0.87)
Ray et al. showed that BNP had a significantly higher area under the
curve for diagnosis of CHF in elderly patients. NT-proBNP utility and Accuracy 0.76 (0.70-0.82) 0.76 (0.69-0.81) 0.83 (0.77-0.88)*†
not BNP utility was compromised by renal insufficiency. BNP improved P < 0.5 vs
the accuracy of the emergency physicians’ diagnoses while NT-proBNP *emergency physician;

did not.4 †proBNP. Adapted from Ray et al.4

Clearance

Triage BNP Presented by

Dr. Robert Christenson, 200510
N=1447
NT-proBNP returns more false positive results resulting in poor + –
McNemar Analysis
specificity and misclassification of severity of heart failure patients. Roche NT-proBNP + 106 FP X2 = 55.1
P-Value = 10-13
425 pg/mL cutoff – 22 FN
VERY SIGNIFICANT

Patient presenting with dyspnea

Physical exam, chest x-ray, ECG, BNP level
BNP has a single FDA cleared 100 pg/mL cut-off and an established
BNP <100 pg/mL BNP 100-500 pg/mL BNP >500 pg/mL
and proven clinical algorithm. BNP cut-offs are clear and consistently
proven.1 HF not very probable Clinical suspicion of HF HF very probable
(2%) or past history of HF? (95%)
HF probable (90%)

CLEAR CONFUSING
BNP NT-proBNP
ALL DIFFERENT

NT-proBNP requires multiple age dependent cut-offs and no simple

CONSISTENT

Manufacturer’s cut-off Manufacturer’s cut-offs

diagnostic algorithm has been established and proven effective 100 pg/mL 125 pg/mL: <75 years; 450 pg/mL: >75 years
in multiple clinical studies. The published NT-proBNP cutoffs are
Cut-offs in literature Cut-offs in literature
different in many studies, which cause confusion.8, 9 Rule out: 100 pg/mL Rule out: 300 pg/mL; Rule in: 3 age dependent
Rule in: 500 pg/mL 450 pg/mL: <50 years; 900 pg/mL: 50-75 years
1800 pg/mL: > 75 years; 10,000 pg/mL: all ages
BNP VS NT-proBNP
Common BNP Objections and How to Respond
“NT-proBNP is more sensitive than BNP”
Sensitivity is cut-off and population dependent.
Some studies suggest that lower BNP cut-offs should be considered for asymptomatic patients.
No natriuretic assay is recommended for screening asymptomatic patients.
One study which evaluated the screening of asymptomatic patients suggested that NT-proBNP had greater sensitivity than BNP
in detecting asymptomatic-structural heart disorders. The results showed that NT-proBNP was elevated in the asymptomatic heart
failure group. However, this group also had greater renal insufficiency, which could have caused the elevation of NT-proBNP.11

“BNP package inserts show that BNP has more false negatives”
The BNP package inserts show more NYHA class I patients with values below 100 pg/mL.
The NYHA class I patient is asymptomatic, and a lower cut-off is recommended for this population.
Package insert comparisons are not head-to-head comparisons of assays in the same population.
NT-proBNP is elevated in all NYHA class patients. In NYHA class I patients, the elevated level of NT-proBNP may or may not be due
to heart failure.

“BNP samples are only stable for 4 – 6 hours”

BNP assays have FDA cleared claims for stability in whole blood or plasma for 8-24 hours. Refer to manufacturers’ package inserts
for details.
24 hour stability is supported by previous reports in literature.12
If samples cannot be run within 24 hours, samples can be separated and frozen for later measurements.

“BNP cannot be used in the setting of Natrecor® (Nesiritide) and NT-proBNP can”
The manufacturer of this drug suggests that blood pressure and not natriuretic peptide measurements should be used to monitor
the patient’s response to Natrecor® infusion.
The BNP Consensus Document suggests that the “rational use of BNP testing is on admission, 24 hours following a major
treatment and at discharge.”
Due to the long half-life of NT-proBNP, NT-proBNP measurements will not reflect changes in response to any therapy, including
nesiritide infusion, until approximately 10 hours after treatment.
Miller et al. studied BNP and NT-proBNP levels in the setting of nesiritide infusion and concluded that neither molecule should be
used to monitor this therapy.

References
1. Silver, et al. BNP Consensus Panel 2004: A clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases,
Congestive Heart Failure. Oct 2004; Vol. 10;Issue 5;Suppl. 3.
2. Mair, et al. The impact of cardiac natriuretic peptide determination on the diagnosis and management of heart failure, Clin Chem Lab Med. 2001;39(7):571-588.
3. Gegenhuber M, et al. Time course of B-Type natriuretic peptide (BNP) and N-Terminal ProBNP changes in patients with decompensated heart failure, Clin Chem. 2004; 50, No. 2.
4. Ray, et al. Comparison of brain natriuretic peptide and probrain natriuretic peptide in the diagnosis of cardiogenic pulmonary edema in patients ages 65 and older. JAGS, 2005;53:643-648.
5. McCullough, et al. B-Type natriuretic peptide and renal function in the diagnosis of heart failure: An analysis from the Breathing Not Properly multinational study. Am J Kidney Dis. 2003; Vol 41, No. 3.
6. Sykes, et al. Analytical relationships among Biosite, Bayer, and Roche methods for BNP and NT-proBNP. AmJ Clin Patho. 2005; 123
7. Fonarow G, et al. The Acute Decompensated Heart Failure National Registry (ADHERETM): Opportunities to improve care of patients hospitalized with acute decompensated heart failure. RICM. 2003;
Vol 4 Suppl. 7
8. Baggish, et al. A clinical and biochemical critical pathway for the evaluation of patients with suspected acute congestive heart failure: The ProBNP investigation of dyspnea in the emergency
department (PRIDE) algorithm. Critical Pathways in Cardiology. Dec 2004: Vol. 3, No. 4: 171-176.
9. Januzzi, et al. The N-Terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) Study. Am J Cardiol. 2005; Vol. 95.
10. Christenson R. Introduction: Evolution of Natriuretic Peptides in Clinical Practice. Presented at Biosite Teleconference Series: Selecting the Right BNP for Your Institution: Clinical and Technical
Considerations. Sep 9, 2005.
11. Mueller T, et al. Head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in symptomatic and asymptomatic structural heart disease. Clinica Chimica Acta 341 (2004) 41-48.
12. Azzazy, et al. Stability of B-Type Natriuretic Peptide (BNP) in Whole Blood and Plasma Stored Under Different Conditions. Abstract presented at AACC meeting 2005.

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