Heart failure (HF) is a common condition and carries a considerable age-dependent all-cause mortality. As a leading cause of hospitalization in adults, ~50% of patients discharged with a diagnosis of HF are readmitted within six months, and the one-year mortality rate is 20% after an initial diagnosis is established. There is currently a chronic HF epidemic with a rapidly expanding prevalence pool of HF patients, which has accounted for increased rates of hospitalization over the past two decades. Accordingly, much effort has been directed toward understanding the pathophysiology of HF, as well as improving diagnostic and therapeutic strategies. The recognition of the natriuretic peptides, in particular B-type natriuretic peptide (BNP), as a marker for the diagnosis, prognosis, and severity of HF has been a major breakthrough. This article will focus on the latest advances in the clinical utility of BNP in a variety of applications.
Natriuretic PeptidesÔÇöImportant 'Heart HormonesÔÇÖ
There are three major natriuretic peptides, all sharing a common 17-amino-acid ring structureÔÇöatrial natriuretic peptide, BNP, and C-type natriuretic peptide. B-type natriuretic peptide is synthesized and stored in the ventricular myocardium as a precursor prohormone. Cleavage of the 32 amino acid sequence by the enzyme corin from the C-terminal end of ProBNP results in the active BNP peptide hormone and the inactive N-terminal fragment of proBNP (NT-proBNP). B-type natriuretic peptide is secreted into the circulation in a pulsatile fashion through the coronary sinuses in response to left ventricular (LV) wall stretch and multiple neurohumoral factors. It has a half-life of 22 minutes and is metabolized by neutral endopeptidase (~30%), and receptor-mediated endocytosis (~70%), which occurs predominantly in the kidney. Normally, BNP levels are slightly higher in women compared with men. Additionally, in the obese, BNP levels are 30% to 50% lower than those of normal body weight, either because of impaired BNP production or increased peripheral clearance of BNP. Both BNP and NT-proBNP have been found in urine. NT-proBNP is not cleared by neutral endopeptidase or by the clearance receptors, hence its clearance is more dependent on glomerular filtration with incomplete resorption, resulting in considerable quantities found in the urine. These urinary levels are high enough to be used as a urinary test for HF. Plasma BNP levels reflect the decompensated state of circulatory congestion and correlate with LV end diastolic pressure and pulmonary capillary wedge pressure. Due to the fact that BNP reflects volume status and has a short half-life, levels reflect dynamic changes in volume attributed to diuresis, making the assay an attractive marker for a variety of conditions associated with LV and right ventricular (RV) dysfunction. The majority of the published studies on clinical applications have utilized BNP; BNP levels will therefore be considered the focus of this article.