What are the reference values for B-type Natriuretic Peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) in heart failure patients?

Reference Values for BNP and NT-proBNP in Heart Failure Patients

For heart failure patients, BNP values >100 pg/mL and NT-proBNP values >300 pg/mL are considered diagnostic of heart failure, with specific age-adjusted thresholds for NT-proBNP providing better diagnostic accuracy. 1

Diagnostic Reference Values

BNP Reference Values:

• Rule-out threshold: <100 pg/mL (excludes acute HF)
• Grey zone: 100-400 pg/mL (raised, suggests HF)
• Rule-in threshold: >400 pg/mL (high, likely HF) 1, 2

NT-proBNP Reference Values:

• Rule-out threshold: <300 pg/mL (excludes acute HF)
• Age-adjusted rule-in thresholds:
  • Age <50 years: >450 pg/mL
  • Age 50-75 years: >900 pg/mL
  • Age >75 years: >1,800 pg/mL 1

Chronic Heart Failure Reference Values

For chronic heart failure patients:

• BNP: <35 pg/mL (to exclude chronic HF)
• NT-proBNP: <125 pg/mL (to exclude chronic HF) 1

For enriching study populations in clinical trials:

• HFpEF (preserved ejection fraction):
  • BNP ≥100 pg/mL
  • NT-proBNP ≥360 pg/mL
• HFrEF (reduced ejection fraction):
  • BNP ≥150 pg/mL
  • NT-proBNP ≥600 pg/mL 1

Special Considerations

Factors Affecting Interpretation:

1. Atrial fibrillation:

   • Increases BNP and NT-proBNP by 20-30% 1

2. Race:

   • Black patients typically have 20-30% lower values 1, 2

3. Age:

   • Elderly patients (>75 years) have 20-30% higher values 1, 2

4. Obesity:

   • BMI ≥30 kg/m² requires lowering thresholds by 20-30%
   • For severe obesity (BMI >35 kg/m²), BNP cut-off of 55 pg/mL is recommended 1

5. Renal dysfunction:

   • GFR <60 mL/min/1.73 m²: Use BNP 200-225 pg/mL or NT-proBNP 1200 pg/mL to rule out HF
   • Accuracy decreases significantly with GFR <30 mL/min/1.73 m² 1

6. Neprilysin inhibition (sacubitril/valsartan):

   • BNP levels may increase by an average of 19%
   • NT-proBNP is preferred for monitoring response to therapy 1

Monitoring and Clinical Significance

• Significant change: Only changes >30-50% from baseline are clinically relevant

  • NT-proBNP: >50% change
  • BNP: >60% change 1

• Ratio: The NT-proBNP to BNP ratio is approximately 6.25:1, but varies with:

  • Atrial fibrillation (8.03:1)
  • Normal rhythm (5.75:1)
  • Age, renal function, and BMI 3

Common Pitfalls

1. Failing to adjust for confounding factors:

   • Not considering age, obesity, renal function, or race when interpreting values

2. Over-reliance on absolute values:

   • Not recognizing that changes >30% are needed to indicate clinical significance

3. Inappropriate assay selection:

   • Using BNP to monitor response to neprilysin inhibitors when NT-proBNP is more reliable in this context

4. Frequent sampling:

   • Unnecessary frequent blood sampling provides little additional value due to biological variability (30-50%)

5. Misinterpreting borderline values:

   • Not considering clinical context when values fall in the "grey zone" (BNP 100-400 pg/mL)

Remember that both BNP and NT-proBNP have high negative predictive values (>95%) for ruling out heart failure, making them most valuable for excluding the diagnosis when levels are below the established thresholds.