Measurement of cardiac natriuretic hormones (atrial natriuretic peptide, brain natriuretic peptide, and related peptides) in clinical practice: The need for a new generation of immunoassay methods

Background: Cardiac natriuretic hormones (CNHs) are a family of related pep tides, including atrial natriuretic peptide (ANP), brain natriuretic peptid e (BNP), and other peptides derived from the N-terminal portion of the proA NP and proBNP peptide chains. Assays for cardiac natriuretic peptides have been proposed to help assess clinical conditions associated with expanded f luid volume. In particular, the assays can be useful for distinguishing hea lthy subjects from patients in different stages of heart failure. Measureme nts of these hormones have also been considered for prognostic indicators o f long-term survival in patients with heart failure and/or after acute myoc ardial infarction. The different CNHs differ in their production/secretion patterns and have different clearance rates. Furthermore, there are numerou s proposed assay configurations for each of these hormones, and it is not c lear which assay provides the best pathophysiological and/or clinical infor mation. Approach: Here we review recent studies concerning the competitive (such as RIA, enzyme immunoassay, or luminescence immunoassay) and noncompetitive i mmunoassays (such as two-site IRMA, ELISA, or immunoluminometric assay) for the different cardiac natriuretic peptides to compare the analytical chara cteristics and clinical relevance of assays for the different CNHs and the different assay formats. Content: Developing sensitive, precise, and accurate immunoassays for cardi ac natriuretic peptides has been difficult because of their low concentrati ons ton average, similar to 3-6 pmol/L) in healthy subjects and because of their structural, metabolic, and physiological characteristics. Competitive assays have historically suffered from lack of sensitivity and specificity for the biologically active peptides. These usually require tedious extrac tion procedures prior to analysis. Recently, immunometric assays have been developed that have improved sensitivity and specificity; it appears these will be the methods of choice. Summary: To date, there is no consensus on the best assay procedure of card iac natriuretic peptides. To facilitate widespread propagation of determina tion of these hormones in routine clinical practice, it will be necessary t o study the new generation of noncompetitive immunometric methods that are less time-consuming and more sensitive and specific. Although several studi es suggest that BNP exhibits better clinical utility than the other CNHs,mo re studies examining multiple CNHs in the; same cohorts of patients will be necessary. (C) 2000 American Association for Clinical Chemistry.