Although applying BNP and NT-proBNP as diagnostic biomarkers of HF has brought significant improvement in treating HF, several confounding factors, such as aging, obesity, anemia, sepsis, hypertension, MI, cardiac hypertrophy, pulmonary hypertension, atrial fibrillation, diabetes mellitus, renal failure, liver cirrhosis, severe burn and cancer chemotherapy, limit their accuracy [165]. This evidence concerns the gene NPPB and obesity due to melanocortin 4 receptor deficiency.