What are the proBNP (pro-brain natriuretic peptide) reference ranges?

ProBNP Reference Ranges

For clinical use, BNP values <35 pg/ml or NT-proBNP values <125 pg/ml are considered normal in chronic settings, while BNP <100 pg/ml or NT-proBNP <300 pg/ml exclude acute heart failure. 1

Normal Reference Ranges

NT-proBNP Reference Ranges

• To exclude chronic heart failure: <125 pg/ml 1
• To exclude acute heart failure: <300 pg/ml 1
• Age-specific cutoffs for acute heart failure diagnosis:
  • Age <50 years: >450 pg/ml
  • Age 50-75 years: >900 pg/ml
  • Age >75 years: >1,800 pg/ml 1

BNP Reference Ranges

• To exclude chronic heart failure: <35 pg/ml 1
• To exclude acute heart failure: <100 pg/ml 1
• For acute heart failure diagnosis: >100 pg/ml (90% sensitivity, 76% specificity) 1
• Strong indicator of heart failure: >400 pg/ml (positive likelihood ratio >10) 1

Special Population Adjustments

Several factors affect natriuretic peptide levels and require threshold adjustments:

1. Age:

   • NT-proBNP increases with age 1
   • For patients >75 years: Consider raising thresholds by 20-30% 1

2. Sex:

   • Males typically have lower values than females 1
   • Normal ranges by sex and age:
     • Ages 45-59: Males <100 pg/ml, Females <164 pg/ml
     • Ages >60: Males <98 pg/ml, Females <225 pg/ml 1

3. Obesity (BMI ≥30 kg/m²):

   • Lower threshold by 20-30% 1
   • For BMI ≥35 kg/m², consider NT-proBNP <50 pg/ml as rule-out threshold 2
   • For BMI ≥35 kg/m², consider NT-proBNP ≥220 pg/ml as rule-in threshold 2

4. Atrial Fibrillation:

   • Increase threshold by 20-30% 1
   • NT-proBNP:BNP ratio is higher (8.03:1 vs 5.75:1 in non-AF) 3
   • NT-proBNP has limited diagnostic value in AF patients as ≥98% with AF and dyspnea have HFpEF 2

5. Race:

   • For Black patients: Consider lowering threshold by 20-30% 1

6. Renal Function:

   • NT-proBNP levels increase with declining renal function 3

Clinical Application in Heart Failure

For Heart Failure with Preserved Ejection Fraction (HFpEF):

• BNP ≥100 pg/ml or NT-proBNP ≥360 pg/ml 1

For Heart Failure with Reduced Ejection Fraction (HFrEF):

• BNP ≥150 pg/ml or NT-proBNP ≥600 pg/ml 1

For Higher Event Rate Prediction:

• BNP >400 pg/ml or NT-proBNP >900 pg/ml 1

For Biomarker Screening in Diabetes:

• Abnormal values: BNP ≥50 pg/ml or NT-proBNP ≥125 pg/ml 1

Important Clinical Considerations

• NT-proBNP has a longer half-life (1-2 hours) compared to BNP (20 minutes) 1
• NT-proBNP has less interassay variability than BNP 1
• The NT-proBNP:BNP ratio is approximately 6.25:1 but varies with clinical factors 3
• Both peptides are similarly predictive of mortality and heart failure outcomes 3
• When using ARNI therapy (sacubitril/valsartan), NT-proBNP is preferred for monitoring as BNP levels can be affected by neprilysin inhibition 1

Pitfalls to Avoid

• Don't rely solely on natriuretic peptides for diagnosis without clinical context
• Be aware of non-heart failure causes of elevated natriuretic peptides (renal insufficiency, pulmonary disease, pulmonary hypertension, COPD, sleep apnea, stroke, anemia) 1
• Recognize that obesity decreases natriuretic peptide levels, which may lead to false negatives 1
• Understand that values in the "gray zone" (NT-proBNP 300-900 pg/ml) still indicate increased mortality risk 1
• Consider that patients may have elevated levels due to non-cardiac causes 4