What is NT-proBNP?
NT-proBNP (N-terminal pro-B-type natriuretic peptide) is an inactive breakdown product released from cardiac myocytes in response to mechanical stretch from volume or pressure overload, serving as a semi-quantitative biomarker for cardiac stress and heart failure diagnosis, prognosis, and treatment monitoring. 1
Biochemistry and Production
NT-proBNP is formed when the heart produces BNP (B-type natriuretic peptide) in response to cardiac stress. The process begins with a pre-prohormone that is split to form proBNP, which is then further broken down into two components: the biologically active hormone BNP 1-32 and the inactive breakdown product NT-proBNP. 1
The primary stimulus for production is myocyte stretch mediated by both pressure and volume overload, with hypoxia also identified as a contributing factor. 1 Production occurs more rapidly and extensively in the ventricles than in the atria, particularly during periods of cardiac strain. 1
Half-Life and Clearance
NT-proBNP has a significantly longer biological half-life compared to BNP:
This longer half-life explains why NT-proBNP values are consistently higher than BNP values and makes NT-proBNP more stable for laboratory testing. 1
NT-proBNP is cleared passively by organs with high blood flow, with the following distribution of total body clearance: 1
- 55-65% by the kidneys
- 20-25% across the liver
- 10-15% across musculoskeletal tissue
- 5-10% across the head and neck
Both BNP and NT-proBNP are extracted renally by 15-20% in healthy individuals, and both increase with renal failure. 1 However, in severe renal dysfunction (GFR <30 mL/min/1.73 m²), NT-proBNP/BNP ratios increase disproportionately. 1
Normal Reference Ranges
NT-proBNP levels vary by age and sex: 1, 2
- Young adults: <70 pg/mL
- Ages 45-59 years: <164 pg/mL (females)
- Ages >60 years: <225 pg/mL (females)
Males consistently have lower levels than females, likely due to androgen suppression of pro-BNP synthesis. 1 Higher body mass index results in lower normal values, though the mechanism remains unclear. 1
Clinical Significance
NT-proBNP is neither heart failure nor heart disease specific - it is a semi-quantitative marker of cardiac stress related to the extent of atrial, ventricular, and valvular dysfunction. 1
Conditions that elevate NT-proBNP include: 1
- Acute or chronic systolic or diastolic heart failure (left and right)
- Valvular heart disease
- Left ventricular hypertrophy with or without hypertension
- Atrial fibrillation
- Pulmonary embolism and severe pulmonary hypertension
- Acute or chronic renal failure
- Advanced liver cirrhosis with ascites
- Anemia and sepsis
- Endocrine disorders (hyperaldosteronism, Cushing's syndrome, hyperthyroidism)
- Severe neurological disease (subarachnoid hemorrhage, stroke, trauma)
Diagnostic Applications
NT-proBNP is primarily used for diagnosis, management, and prognostication of cardiac failure. 1 The biomarker has high sensitivity for ruling out heart failure at lower thresholds and strong positive predictive value at higher thresholds. 3
Age-adjusted diagnostic cut-offs for acute heart failure: 2
- **<50 years**: >450 pg/mL
- 50-75 years: >900 pg/mL
- >75 years: >1,800 pg/mL
For exclusion of heart failure, NT-proBNP <300 pg/mL has a 98% negative predictive value. 3, 2
Prognostic Value
NT-proBNP should be interpreted as a continuous variable, with higher values indicating greater risk regardless of the underlying cause. 1, 3 For each 500 pg/mL increase in NT-proBNP above baseline in patients with mild to moderate cardiac failure, there is an associated 3.8% increased mortality risk. 2
Sample Stability
NT-proBNP is more stable than BNP for laboratory testing. 1 The biomarker is stable at room temperature for at least 2 days, with long-term stability of at least 4 months at -20°C and at least 1 year at -80°C. 1
Important Caveats
Obesity can lead to lower NT-proBNP levels, potentially masking cardiac dysfunction. 3, 2 Renal dysfunction elevates values, particularly for NT-proBNP compared to BNP. 2 Acute conditions like sepsis and atrial fibrillation can affect accuracy and interpretation. 3