Can infections cause a false rise in N-terminal pro b-type natriuretic peptide (NT-proBNP) levels?

Infections Can Cause False Elevation in NT-proBNP Levels

Yes, infections can cause a false rise in NT-proBNP levels, even in the absence of heart failure or cardiac dysfunction. This is a clinically significant consideration when interpreting NT-proBNP results in patients with suspected heart failure who also have concurrent infections.

Mechanism and Evidence

• Systemic infections and inflammatory states can directly increase NT-proBNP levels through several mechanisms:

  • Inflammatory cytokines may stimulate BNP production
  • Endotoxins from bacterial infections can trigger NT-proBNP release
  • Sepsis-induced hemodynamic changes can cause cardiac stress 1

• In a controlled study, even healthy individuals with normal cardiac function showed significant increases in NT-proBNP levels after administration of E. coli endotoxin, demonstrating that infection/inflammation alone can elevate NT-proBNP 1

• The elevation correlates with inflammatory markers like C-reactive protein (CRP) and body temperature, not just with cardiac parameters 1

Magnitude of Elevation

• In patients with infectious diseases, NT-proBNP levels can be significantly elevated (median: 193 pg/mL) compared to baseline, though typically not as high as in primary cardiac disease (median: 548 pg/mL) 2

• In community-acquired infections, NT-proBNP levels can reach an average of 5897 pg/mL compared to 108 pg/mL in healthy controls 3

• Lower respiratory tract infections tend to cause the highest elevations in NT-proBNP compared to other infection sites 3

Clinical Implications

• When interpreting NT-proBNP in patients with suspected heart failure:

  • Rule-out cutoffs remain reliable (<100 pg/mL for BNP, <300 pg/mL for NT-proBNP) even in the presence of infection 4
  • Rule-in cutoffs (>400 pg/mL for BNP) should be interpreted with caution in patients with active infections 4, 5

• In septic patients, NT-proBNP shows a biphasic pattern:

  • Initial elevation in all septic patients regardless of cardiac function
  • Persistent elevation on day 2 and beyond suggests actual cardiac dysfunction 6

Other Non-Cardiac Causes of NT-proBNP Elevation

Beyond infections, other conditions that can falsely elevate NT-proBNP include:

• Renal dysfunction (impairs clearance)
• Advanced age
• Atrial fibrillation
• Pulmonary embolism
• Pulmonary hypertension
• Sepsis
• Critical illness 4, 5

Practical Approach to Interpretation

1. Consider pre-test probability of heart failure vs. infection

2. Use lower thresholds for excluding heart failure (<100 pg/mL for BNP, <300 pg/mL for NT-proBNP)

3. In patients with values in the "gray zone" (100-400 pg/mL for BNP):

   • Look for clinical evidence of infection (fever, elevated WBC, CRP)
   • Consider echocardiography to directly assess cardiac function
   • Serial measurements may help differentiate - persistent elevation beyond 48-72 hours after treating infection suggests cardiac etiology 6

4. In critically ill patients with both suspected heart failure and infection:

   • Use NT-proBNP as part of a comprehensive assessment
   • Higher values correlate with worse outcomes regardless of cause 3
   • Consider age-adjusted cutoffs for NT-proBNP (450 pg/mL for <50 years, 900 pg/mL for 50-75 years, 1800 pg/mL for >75 years) 4

Remember that NT-proBNP elevation in infection is not truly "false" but reflects actual cardiac stress, even if transient and not indicative of chronic heart failure.