Can chronic low ferritin levels cause elevated N-terminal pro b-type natriuretic peptide (NT-proBNP) readings?

Relationship Between Chronic Low Ferritin Levels and Elevated NT-proBNP Readings

Yes, chronic low ferritin levels can cause elevated NT-proBNP readings, as demonstrated by research showing that iron deficiency is associated with increased NT-proBNP levels even in the absence of heart failure or anemia. 1

Mechanisms Linking Iron Status and NT-proBNP

Iron Deficiency (Low Ferritin)

• Low ferritin levels indicate iron deficiency, which can lead to elevated NT-proBNP through several mechanisms:
  • Direct impact on myocardial function and metabolism
  • Increased cardiac wall stress even before overt heart failure develops
  • Compensatory mechanisms that affect cardiac workload
  • Potential subclinical myocardial dysfunction 2

Evidence Supporting This Relationship

• Patients with low ferritin levels (<30 ng/mL) have a significantly higher risk of heart failure (HR = 2.24) compared to those with normal ferritin levels, even after excluding patients with anemia 3
• Anemic patients without heart failure or renal disease have significantly higher NT-proBNP concentrations compared to non-anemic patients (232 vs. 82 ng/L) 1
• Intravenous iron therapy in anemic patients with heart failure and renal insufficiency substantially reduced NT-proBNP levels (from ~450 pg/mL to ~117 pg/mL) without requiring erythropoietin 2

Interpreting NT-proBNP in the Context of Iron Status

Considerations for NT-proBNP Interpretation

• NT-proBNP is a quantitative marker related to cardiac stress and heart failure, secreted in response to volume/pressure overload 4
• When evaluating elevated NT-proBNP levels, iron status should be assessed as a potential contributing factor 5
• Age-specific cutoff values for NT-proBNP in heart failure diagnosis should be considered:
  • Age <50 years: >450 ng/L
  • Age 50-75 years: >900 ng/L
  • Age >75 years: >1800 ng/L 5

Common Pitfalls in Interpretation

• Failing to consider non-cardiac causes of NT-proBNP elevation, including iron deficiency and anemia 5
• Interpreting a single NT-proBNP value without clinical context 5
• Not recognizing that anemia can lead to NT-proBNP elevations that exceed diagnostic cutoffs, independent of heart failure 1, 6

Clinical Approach to Elevated NT-proBNP with Low Ferritin

Diagnostic Evaluation

1. Assess for symptoms of heart failure (peripheral edema, pulmonary rales, increased jugular venous pressure)
2. Evaluate iron status with complete iron studies (ferritin, transferrin saturation, total iron binding capacity)
3. Check hemoglobin levels to identify concurrent anemia
4. Consider echocardiography to assess cardiac structure and function 5

Management Considerations

1. Address iron deficiency:

   • For patients with heart failure and iron deficiency, intravenous iron therapy may reduce NT-proBNP levels and improve cardiac function 2
   • Iron repletion should be considered even in patients without overt anemia if ferritin is low 3

2. Monitor response:

   • Serial measurements of NT-proBNP after iron repletion can help assess treatment efficacy
   • A reduction >30% in NT-proBNP following treatment indicates a good prognosis 5

Bidirectional Relationship

It's important to note that both iron deficiency (low ferritin) and iron overload (very high ferritin) can be associated with elevated NT-proBNP levels and increased risk of heart failure 3, 7. This suggests a U-shaped relationship between iron status and cardiac function, with optimal cardiac health requiring balanced iron homeostasis.

In summary, when evaluating elevated NT-proBNP levels, clinicians should consider iron deficiency as a potential contributing factor, even in patients without overt heart failure or anemia.