Diagnostic and prognostic considerations for use of natriuretic peptides in obese patients with heart failure

Abstract

Natriuretic peptides (NPs, B-type natriuretic peptide /BNP and NT-proBNP) are universally used biomarkers with established cut-points to aid in the diagnosis of heart failure (HF). It has been demonstrated that an inverse relationship exists between obesity, defined by the body mass index (BMI), and NPs, such that the application of NPs to diagnostic algorithms in HF remains challenging in overweight and obese patients. Some have advocated that lowering the cut-offs for NPs or using a correction for high BMI may improve the diagnostic accuracy in obese individuals. The inverse relationship of NPs with high BMI is present in both HF with reduced (HFrEF) and with preserved (HFpEF) ejection fraction, although levels tend to be higher in HFrEF. Nevertheless, data from several studies have shown that the prognostic value of NPs is preserved across BMI classes, and that increasing circulating levels of NPs correlate with adverse outcomes including all-cause mortality and HF hospitalizations. While NPs can still be used in diagnosis of HF in obese individuals, lower thresholds and the clinical context should be utilized in decision making. Additionally, given the validated prognostic value even in obesity, NPs can be employed in risk-stratification of individuals with obesity and HF, although there remains limited evidence about use in those with severe obesity (BMI >40 kg/m²).

Keywords: B-type natriuretic peptide; Heart failure; Natriuretic peptides; Obesity.

Figure 1. Mechanistic Model for Effects of Obesity on Cardiac Dysfunction and HF

Model depicting the feedback loop between adipose tissue and cardiac tissue. NPs released by cardiomyocytes have a favorable effect on body fat distribution through various mechanisms. A deficiency of NPs in obese individuals with excessive fact accumulation leads to adverse obesogenic states (increased visceral and epicardial fat), which in turn result in cardiac dysfunction via myocardial wall stress and injury. LBAT = lower body subcutaneous adipose tissue; VAT=visceral adipose tissue. Reproduced from reference with permission.

Figure 2. Association between BMI and NP Z-score in chronic HFpEF

A U-shape association is shown between BMI and NP levels in patients with chronic HFpEF, in the secondary analysis of the TOPCAT trial. NPs were either measured as BNP or NT-proBNP, therefore a single, combined, log-transformed Z-score was calculated. Reproduced from reference with permission.

Figure 3. Algorithm for utilizing NPs for diagnosis of HF with consideration for BMI

This algorithm proposes stratifying patients based on BMI prior to interpreting NP levels. In overweight and obese individuals, a lower cut-off for BNP should be used for the diagnosis of HF. There are no proposed cut-offs for NT-proBNP in these individuals, and up to 50% reduction in existing cut-offs can be used based on clinical judgement with utilization of other clinical findings.