Can Brain Natriuretic Peptide (BNP) levels be falsely low in obese individuals?

BNP Levels Are Falsely Low in Obese Patients with Heart Failure

Yes, BNP levels can be falsely low in obese individuals, requiring adjusted interpretation and potentially lower diagnostic thresholds in this population.

Mechanism and Evidence

BNP (Brain Natriuretic Peptide) and its N-terminal fragment (NT-proBNP) are important biomarkers for diagnosing heart failure. However, obesity significantly impacts their interpretation:

• The American Heart Association confirms that BNP levels are lower in obese patients even when they have heart failure with the same severity as non-obese patients 1
• For any given left ventricular diastolic pressure, BNP levels are lower in obese patients compared to non-obese patients with heart failure 1
• This inverse relationship between BMI and BNP levels persists even after adjusting for relevant covariates 2

Clinical Implications

Diagnostic Challenges

• Using standard BNP cutoffs in obese patients can lead to missed diagnoses:
  • At the standard cutoff of 100 pg/mL, BNP testing was falsely negative in approximately 20% of heart failure cases in both overweight and obese patients 2
  • For NT-proBNP, using a cut point of 900 pg/mL resulted in false negatives in up to 15% of heart failure cases in obese patients (BMI ≥30 kg/m²) 2

Adjusted Thresholds

• BMI-specific cutoffs have been proposed to maintain diagnostic sensitivity:
  • For BNP: 170 pg/mL for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL for severely/morbidly obese patients 3
  • The European Society of Cardiology recommends a lower cutoff of 55 pg/mL for patients with BMI >35 kg/m² 4

Physiological Explanation

Several mechanisms may explain lower BNP levels in obese patients:

• Increased BMI is associated with decreased concentrations of proBNP not glycosylated at threonine 71 (NG-T71), which could partially explain the lower NT-proBNP and BNP concentrations in obese individuals 5
• There appears to be a BMI-related defect in natriuretic peptide secretion 2
• Obese patients with heart failure have lower end-diastolic wall stress, which is a major stimulus for BNP secretion, though BMI remains independently associated with lower BNP levels even after accounting for wall stress 6

Clinical Recommendations

When interpreting BNP or NT-proBNP in obese patients:

1. Recognize that standard cutoff values may not apply
2. Consider using lower diagnostic thresholds:
   • For BNP: approximately 54-60 pg/mL in severely obese patients (BMI ≥30 kg/m²) 3
   • For NT-proBNP: consider adjusting thresholds downward by approximately 50% in obese patients 4
3. Integrate clinical assessment with biomarker results, particularly in obese patients where biomarker levels may be misleadingly low
4. Consider additional diagnostic testing when clinical suspicion for heart failure is high despite "normal" BNP levels in obese patients

Common Pitfalls to Avoid

• Excluding heart failure diagnosis based solely on "normal" BNP levels in obese patients
• Failing to adjust diagnostic thresholds based on BMI
• Not recognizing that the inverse relationship between BMI and natriuretic peptide levels applies to both BNP and NT-proBNP
• Overlooking that this phenomenon occurs in both acute and chronic heart failure settings

Understanding this relationship is critical for accurate diagnosis and appropriate management of heart failure in the growing population of patients with obesity.