Analytical Performance and Diagnostic Accuracy of Immunometric Assays for the Measurement of Plasma B-Type Natriuretic Peptide (BNP) and N-Terminal proBNP

Abstract

Over the last 5 years, several immunoassay methods for the measurement of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) became commercially available. Recent studies have confirmed the clinical usefulness of measurements of these cardiac natriuretic peptides for the prognostic stratification of patients with congestive heart failure, for the detection of left ventricular systolic and/or diastolic dysfunction, and for the differential diagnosis of dyspnea (1-4 ). However, to answer the most urgent requests of current clinical practice and to allow widespread use of BNP and NT-proBNP assays, some key issues had to be solved, such as increasing the sensitivity, precision, and experimental practicability (5 ). The aim of the present study was to evaluate and compare the analytical and clinical performance of five commercial natriuretic peptide immunoassays.Throughout this report, the values in healthy individuals and patients are reported as the range, median, and 25th and 75th percentiles. We enrolled 172 healthy adults (89 women and 83 men; age range, 16 -73 years; median age, 49.0 years; 25th percentile, 38 years; 75th percentile, 58 years). All participants were nonobese (body mass index, 19.4 -27.6 kg/m 2 , 24 kg/m 2 , 22.8 kg/m 2 , and 25.6 kg/m 2 ), normotensive (diastolic blood pressure, 60 -85 mmHg, 70 mmHg, 70 mmHg, and 80 mmHg; systolic blood pressure, 90 -140 mmHg, 120 mmHg, 102.5 mmHg, and 124.5 mmHg), and free from acute or chronic diseases. All participants had main plasma indices (including creatinine, urea nitrogen, glucose, uric acid, albumin, enzymes, electrolytes, and hemoglobin) within the appropriate reference intervals, and normal erythrocyte and leukocyte counts and urine analyses. All were asymptomatic and underwent a complete examination by a cardiologist, including a visit, standard 12-lead electrocardiogram, Doppler echocardiographic examination, and a bicycle stress test (when older than 50 years), which excluded silent heart disease.We also prospectively evaluated 279 consecutive patients with heart failure (211 men and 68 women; age, 20 -89 years, 66.0 years, 57.3 years, and 73 years). Cardiac morphology and function were assessed by two-dimensional echocardiography, or cardiac catheterization when needed. Idiopathic dilated cardiomyopathy was diagnosed in 136 patients (48.7%), whereas the other 143 patients suffered from secondary cardiomyopathy. Of these, 126 (45.1%) had ischemic cardiomyopathy. The inclusion criterion was a depressed (Ͻ50%) left ventricular ejection fraction [mean (SD), 31.8 (9.4)%; range, 10 -48%]. Heart failure severity was evaluated clinically according to the New York Heart Association (NYHA) classification: 32 patients were in functional NYHA class I, 133 were in class II, 81 were in class III, and 33 were in class IV, respectively. Patients were treated with a multidrug treatment (78% of patients treated with frusemide, 94% with angiotensin-converting enzyme inhibitor, 70% with carvedilol, and 58% with spironolactone), which was not stoppe...

Comparison of the Diagnostic Accuracy of Brain Natriuretic Peptide (BNP) and the N-Terminal Part of the Propeptide of BNP Immunoassays in Chronic and Acute Heart Failure: A Systematic Review

“…The use of BNP or NT-proBNP measurement in clinical practice requires the commercial availability of robust and fully automated immunoassay methods (3,7,8 ). Although several studies have been published recently on the biochemical characteristics and pathophysiological relevance of BNP and NT-proBNP, no systematic reviews have been reported that specifically aimed to compare the diagnostic accuracy of commercial immunoassays for different B-type related natriuretic peptides.…”

“…Several recent studies suggested that the diagnostic accuracy of CNH immunoassay methods depends not only on the peptide measured but also on the platform used (3,7,8 ). Commercial immunoassays for BNP use different standard materials and antibodies that are specific for different epitopes located on the N-terminus, C-terminus, or cysteine-ring of the peptide chain (8 ).…”

“…Commercial immunoassays for BNP use different standard materials and antibodies that are specific for different epitopes located on the N-terminus, C-terminus, or cysteine-ring of the peptide chain (8 ). Experimental data support the hypothesis that BNP is cleaved by several plasma proteases; therefore, these enzymatic cleavages, particularly the one at the N-terminus, must be considered when choosing epitopes for antibody production and immunoassay design (3,7,8 ). Because of their different biochemical and physiological characteristics, BNP and NT-proBNP measurements may have different advantages (1,3 ).…”

Clinical Relevance of Biological Variation of B-Type Natriuretic Peptide

“…According to this approach, the assay imprecision of BNP immunoassays should be as low as possible. A recent study from our laboratory evaluated the analytical imprecision of several commercial BNP immunoassays (12 ). On average, this study demonstrated that analytical performance, as well as reference and decision values, varied greatly among the BNP assay methods; in particular, the imprecision of these immunoassays varied, on average, from ϳ15% (the worst) to 5% (the best) (12 ).…”

“…A recent study from our laboratory evaluated the analytical imprecision of several commercial BNP immunoassays (12 ). On average, this study demonstrated that analytical performance, as well as reference and decision values, varied greatly among the BNP assay methods; in particular, the imprecision of these immunoassays varied, on average, from ϳ15% (the worst) to 5% (the best) (12 ). Evidently, the immunoassay with the best imprecision is able to detect significantly narrower changes in BNP concentrations (i.e., variations of ϳ15% for the method with the lowest imprecision).…”