B-type natriuretic peptide (BNP) has reduced specificity for heart failure with preserved ejection fraction (HFpEF), for example, in obesity, increased clearance of BNP and NT-proBNP via the natriuretic peptide clearance receptor (NPR-C), and enhanced degradation by neprilysin contribute to lower circulating levels. This evidence concerns the gene NPPB and obesity due to melanocortin 4 receptor deficiency.