What is the difference between B-type Natriuretic Peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-PRO BNP)?

Differences Between BNP and NT-proBNP

BNP and NT-proBNP are both cardiac biomarkers derived from the same precursor molecule, but they differ significantly in their half-life, stability, clearance mechanisms, and clinical cutoff values.

Origin and Processing

• Both markers originate from proBNP (108 amino acids), which is produced by cardiac ventricular myocytes in response to wall stretch and increased mechanical load 1
• Under normal circumstances, proBNP is cleaved into:
  • Active BNP (32 amino acids) - the biologically active hormone
  • NT-proBNP (76 amino acids) - the inactive N-terminal fragment 1

Key Differences

Half-Life and Stability

• BNP:

  • Shorter half-life of 13-20 minutes 1
  • Less stable in vitro (stable for only about 4 hours at room temperature) 1
  • Requires EDTA whole blood or plasma collected in plastic tubes 1
  • Should be measured as soon as possible (within 4 hours) after collection 1

• NT-proBNP:

  • Longer half-life of 25-70 minutes (approximately 3-5 times longer than BNP) 1
  • Much more stable in vitro (stable at room temperature for at least 2 days) 1
  • Can be measured in serum or heparin plasma 1
  • Long-term stability of frozen samples is at least 4 months at -20°C and at least 1 year at -80°C 1

Clearance Mechanisms

• BNP:

  • Cleared actively via clearance receptors (NP receptor-C)
  • Also degraded by neutral endopeptidase (EC 3.4.24.11) 1

• NT-proBNP:

  • Cleared passively by organs with high blood flow
  • 55-65% cleared by kidneys
  • 20-25% cleared by liver
  • 10-15% cleared by musculoskeletal tissue
  • 5-10% cleared by head and neck 1

Reference Values and Cutoffs

• BNP:

  • Generally lower values than NT-proBNP 1
  • Rule-out cutoff for heart failure: 100 ng/L
  • Rule-in cutoff for heart failure: 500 ng/L 1
  • For patients with GFR <60 mL/min/1.73 m², a higher cutoff of 200-225 ng/L is recommended 1

• NT-proBNP:

  • Higher values than BNP due to longer half-life 1
  • Age-independent rule-out cutoff: 300 ng/L
  • Age-dependent rule-in cutoffs:
    • <50 years: >450 ng/L
    • 50-75 years: >900 ng/L

    • 75 years: >1800 ng/L 1

  • For patients with GFR <60 mL/min/1.73 m², a higher cutoff of 1200 ng/L is recommended 1

Clinical Considerations

Assay Characteristics

• NT-proBNP assays are more standardized (predominantly one source of antibodies and calibrators from Roche) 1
• BNP assays have more variability between manufacturers 1
• Both markers are affected by renal function, with increased levels in renal dysfunction 1

Special Populations

• Both markers are affected by:
  • Age (higher in elderly)
  • Sex (higher in females)
  • BMI (lower in obese patients) 2, 3
• For obese patients (BMI >35 kg/m²), a lower BNP cutoff of 55 ng/L is recommended 1

Specific Clinical Scenarios

• When using nesiritide (recombinant BNP) for treatment, BNP levels will be artificially elevated, making NT-proBNP the preferred biomarker for monitoring 1
• In patients receiving sacubitril/valsartan, BNP levels may remain stable while NT-proBNP decreases due to differences in clearance mechanisms 4

Common Pitfalls

• Using a single cutoff value for all patients without considering age, sex, and renal function 2
• Not accounting for obesity, which can lower both markers 1, 2
• Failing to recognize that both markers can be elevated in non-cardiac conditions (renal failure, sepsis, liver disease) 1
• Not considering the timing of blood collection and sample handling, particularly for BNP 1

Both BNP and NT-proBNP are excellent biomarkers for ruling out heart failure, with high negative predictive values when below their respective cutoffs. The choice between them often depends on local availability, laboratory preferences, and specific clinical scenarios.