From the Guidelines
Obesity decreases levels of BNP and NT-proBNP, and clinicians should consider using lower diagnostic thresholds for these biomarkers in obese patients to maintain diagnostic sensitivity. The primary mechanism involves increased expression of natriuretic peptide clearance receptors (NPR-C) in adipose tissue, which leads to enhanced removal of these peptides from circulation, as supported by the most recent study 1. Additionally, adipose tissue produces neprilysin, an enzyme that degrades natriuretic peptides. Obese individuals also experience reduced cardiac production of BNP and NT-proBNP due to decreased cardiac wall stress, as adipose tissue can provide a cushioning effect that reduces ventricular strain despite increased blood volume.
Some key points to consider include:
- The inverse relationship between body mass index and natriuretic peptide levels is clinically significant because it may lead to underdiagnosis of heart failure in obese patients when using standard diagnostic cutoffs 2.
- Insulin resistance, commonly associated with obesity, may further suppress natriuretic peptide production through impaired transcription of the natriuretic peptide gene.
- A study published in 2020 1 recommends considering lowering enrollment threshold by at least 20%-30% for patients with BMI ≥30 kg/m² when using BNP and NT-proBNP as clinical trial inclusion criteria.
- The prevalence of obesity in HFpEF is well known, and natriuretic peptides are also key neurohormonal modifiers of HFpEF development, with obese patients with HFpEF having particularly low concentrations of BNP and NT-proBNP 1.
Overall, the relationship between obesity and natriuretic peptide levels is complex, and clinicians should be aware of the potential for underdiagnosis of heart failure in obese patients when using standard diagnostic cutoffs. Using lower diagnostic thresholds for BNP and NT-proBNP in obese patients is essential to maintain diagnostic sensitivity, as supported by the most recent and highest quality study 1.
From the Research
Obesity and Natriuretic Peptides
- Obesity is associated with lower levels of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with heart failure 3, 4, 5, 6, 7
- The inverse relationship between BNP and NT-proBNP levels and body mass index (BMI) is complex and not fully understood 5
- Studies have shown that obese patients with heart failure have lower levels of BNP and NT-proBNP compared to non-obese patients, which can lead to underdiagnosis or misdiagnosis of heart failure 3, 4, 6
Mechanisms and Diagnostic Implications
- The mechanism of natriuretic peptide suppression in obese patients is not fully understood, but it is thought to be related to the cardiac endocrine paradox in heart failure 5
- The use of BNP and NT-proBNP as diagnostic tools for heart failure may have reduced sensitivity in obese patients, particularly in those with preserved ejection fraction 6, 7
- NT-proBNP levels may be falsely negative in up to 15% of obese patients with acute congestive heart failure, and BNP testing may be falsely negative in up to 20% of overweight and obese patients with heart failure 6
Clinical Implications
- Clinicians should exercise caution when interpreting BNP and NT-proBNP levels in obese patients with suspected heart failure 3, 4, 5, 6, 7
- The diagnosis of heart failure should not be excluded solely based on low NT-proBNP levels in overweight and obese patients 7
- Further research is needed to understand the relationship between obesity, BNP, and NT-proBNP levels, and to develop more effective diagnostic strategies for heart failure in obese patients 5