Background: Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event.

An early-discharge strategy using an hs-TnI assay and TIMI score ≤ 1 had similar safety as previously reported, with the potential to decrease the observation periods and admissions for approximately 40% of patients with suspected ACS. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study, NCT00470587; A 2 hr Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker [ADAPT]: a prospective observational validation study, ACTRN12611001069943).

B-type natriuretic peptide (BNP) is a 32 amino acid cardiacsynthesized hormone that reduces blood pressure and increases sodium excretion (1 ). Following proteolytic cleavage of proBNP, a 108-amino acid precursor, an Nterminal fragment (NT-proBNP) and BNP are released (2 ). Increased concentrations of BNP and NT-proBNP can be used clinically to monitor heart failure, but a lack of alignment between commercial BNP and NT-proBNP assays (3 ) can lead to confusion when clinicians or laboratorians compare results measured for the same analyte on different instruments. Some of this confusion arises from variable assay specificity regarding what peptides are being measured. We studied whether (a) BNP assays demonstrated crossreactivity with NT-proBNP or proBNP, and (b) whether NTproBNP assays demonstrated crossreactivity with BNP or proBNP, by using 5 commercial BNP and 3 commercial NT-proBNP assays with 2 BNP, 2 NT-proBNP, and 2 proBNP materials.The NPs studied were: Peptide Institute synthetic BNP (aa 77-108), Scios human recombinant BNP (aa 77-108), HyTest human recombinant NT-proBNP (aa 1-76), Roche modified (amidated for stabilization) synthetic NTproBNP, HyTest human recombinant proBNP (aa 1-108), and Scios glycosylated human recombinant proBNP. BNP assays evaluated were Abbott Architect, Abbott AxSYM, Bayer Centaur, Biosite Triage, and Beckman Access (Biosite assay packaged for use by Beckman). NT-proBNP assays (all based on Roche reagents) were Dade-Behring Dimension, OrthoClinical Diagnostics Vitros, and Roche Elecsys 2010. All assays, for which epitopes of the antibodies used have been previous described (3 ), were run according to the manufacturers' guidelines. BNP, NT-proBNP, and proBNP materials were diluted with normal (low NP concentration) EDTAplasma pools and lithium-heparin plasma (Dade assay only) pools, collected from healthy donors after institutional review board approval was obtained, to achieve target concentrations of 250, 500, and 1000 ng/L. Baseline BNP and NT-proBNP were quantified first in the pools and then after the pools were spiked with NP peptides. All measurements were performed in duplicate. Baseline BNP or NT-proBNP concentrations were subtracted from each spiked pool measurement. Percent crossreactivity was calculated by dividing the measured concentration for the spiked pool into the expected peptide concentration, multiplying by 100, and then averaging across all 3 expected concentrations.Recoveries and cross-reactivity percentages between peptides and BNP and NT-proBNP assays are displayed in Table 1. The BNP assays were more specific for the BNP peptides, with recovery ranging from 79% to 199%, compared to 5% to 38% cross-reactivity to the proBNP peptides and Ͻ1% to 7% cross-reactivity to the NTproBNP peptides. Similarly, the NT-proBNP assays were more specific for the NT-proBNP peptides, showing 47% to 243% recovery, with substantial crossreactivity to proBNP peptides (Ͻ1% to 249%), and no crossreactivity to the BNP peptides (Ͻ1% across all assays).This study demonstrates th...

Background:The objective of this report is to improve the quality of immunochemical measurements of B-type natriuretic peptide (BNP) and its N-terminal propeptide (NT-proBNP). The recommendations proposed are intended for use by manufacturers of commercial assays, by clinical laboratories using those assays, by clinical trial groups and research investigators, and by regulatory agencies, such as the United States Food and Drug Administration. Methods: A group of cardiac biomarker experts reviewed and abstracted the scientific literature to provide recommendations pertaining to the quality specifications for BNP/NT-proBNP assays. Results: The evidence-based recommendations encourage manufacturers to endorse and consistently follow the proposed recommendations; encourage that all package inserts for BNP/NT-proBNP immunoassays include uniform information on assay design, preanalytical performance characteristics, analytical performance characteristics, and clinical performance; and encourage regulatory agencies to adopt a minimal and uniform set of criteria for manufacturers to provide when seeking clearance for new and/or improved assays. Conclusions: These recommendations address the use of BNP and NT-proBNP as cardiac biomarkers and not their physiologic and/or pathophysiologic relevance.

Background: As part of the NIH/National Heart, Lung and Blood Institute Contract for the Standardization of Lipoprotein(a) [Lp(a)] Measurements, a study was performed in collaboration with the IFCC Working Group for the Standardization of Lp(a) Assays. The aims of the study, performed with the participation of 16 manufacturers and 6 research laboratories, were to evaluate the IFCC proposed reference material (PRM) for its ability to transfer an accuracy-based value to the immunoassay calibrators and to assess concordance in results among different methods. Methods: Two different purified Lp(a) preparations with protein mass concentrations determined by amino acid analysis were used to calibrate the reference method. A Lp(a) value of 107 nmol/L was assigned to PRM. After uniformity of calibration was demonstrated in the 22 evaluated systems, Lp(a) was measured on 30 fresh-frozen sera covering a wide range of Lp(a) values and apolipoprotein(a) [apo(a)] sizes. Results: The among-laboratory CVs for these samples (6–31%) were, in general, higher than those obtained for PRM (2.8%) and the quality-control samples (14%, 12%, and 9%, respectively), reflecting the broad range of apo(a) sizes in the 30 samples and the sensitivity of most methods to apo(a) size heterogeneity. Thus, although all of the assays were uniformly calibrated through the use of PRM, no uniformity in results was achieved for the isoform-sensitive methods. Conclusions: Linear regression analyses indicated that to various degrees, apo(a) size heterogeneity affects the outcome of the immunochemical methods used to measure Lp(a). We have also shown that the inaccuracy of Lp(a) values determined by methods sensitive to apo(a) size significantly affects the assessment of individual risk status for coronary artery disease.

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