B-type natriuretic peptides as powerful markers in cardiac diseases: Analytical and clinical aspects

Among all natriuretic peptides and neurohormones, B-type natriuretic peptide (BNP) and its Nterminal prohormone fragment (NT-proBNP) have been shown to be the best and most powerful markers to identify patients with acute and chronic heart failure (HF). The fully automated BNP and NT-proBNP assays require only 15-20 min to achieve a test result so that a turn-around time of less than 60 min is possible, as requested by the guidelines of the cardiological societies. The in-vitro stabilities of BNP and NT-proBNP are sufficient for routine use. Most of the commercially available assays, except if they are sublicensed, use different antibodies. This may explain that in general, BNP and NT-proBNP assays show close correlations, but do not agree in absolute values. The assays have not been standardized so far and the application of various calibration materials may contribute to different results. Thus, reference ranges are dependent on the assay used, and reference ranges have to be determined for each assay separately. The increasing values with age may be related to the increasing frequency of subclinical renal or cardiac dysfunction in the elderly. Estrogens stimulate the natriuretic peptide production in females, and reference ranges depend on sex from adolescence to menopause. Immediately after birth, BNP and NTproBNP levels are substantially higher in neonates than in their mothers. The high biological variation of natriuretic peptides must be considered when interpreting serial BNP and NT-proBNP results. Therefore, only marked BNP or NT-proBNP changes during follow-up are related to changes in the clinical HF status. A conclusion of all major studies is that in patients with chronic HF BNP and NT-proBNP are rather rule-out than rule-in markers because of limited cardiac specificities. Patients with acute HF usually show higher BNP and NT-proBNP levels than patients with chronic HF. The greatest efficiency of BNP and NT-proBNP testing was demonstrated in patients presenting to the emergency department with acute dyspnoea or in outpatients with symptoms suggesting chronic HF. Many studies indicate that short- and long-term prognosis in HF can be assessed by BNP or NT-proBNP determination. These hormones are independent predictors of death or HF hospitalizations. Natriuretic peptides are increased in all diseases affecting the cardiac or renal function and fluid balance. BNP and NT-proBNP are markers of cardiac dysfunction in patients with renal failure as well, but higher decision limits have to be used. Decreased BNP and NT-proBNP concentrations in obesity are not fully understood and controversial reports are found in the literature. In summary, BNP or NT-proBNP determination is a powerful test for ruling out HF. Furthermore, these markers are a useful addition to the standard clinical investigations of patients with suspected ventricular dysfunction.