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Letters to the Editor |
Endocrine Unit, Ospedale "Luigi Sacco", Via G.B. Grassi 74, 20157 Milan, Italy
Dept. of Cardiovascular Res., Ist. di Ricerche Farmacol. "Mario Negri", Milan, Italy
To the Editor:
Brain natriuretic peptide (BNP) is a 32-amino acid peptide structurally related to atrial natriuretic peptide and predominantly secreted by myocardial ventricles. Interest in this peptide has recently increased because its concentration carries prognostic value in patients with myocardial infarction [1], congestive heart failure (CHF) [2], or cardiac hypertrophy [3]. The circulating concentration of BNP is also a predictor of mortality, independently of cardiovascular disease [4]. Three commercially available immunoassay methods are designed to measure the plasma concentration of human BNP: two recent nonextraction assays and an older extraction RIA. Here, we compared these three immunoassays and correlated them to cardiac function in healthy volunteers and patients with CHF.
We studied 26 patients (15 men, 11 women; ages 51–84) with depressed left ventricular function and a wide range of ejection fractions (22–57%) measured by bidimensional echo-Doppler technique. Six volunteers without evidence of cardiovascular disease were also included in the evaluation. Blood samples (14–21 mL) were collected in chilled tubes containing EDTA-sodium and aprotinin (500 kallikrein inhibitor units/mL), and the plasmas obtained were immediately separated and stored in aliquots at -80 °C until assay. Each plasma sample was assayed for BNP with a nonextraction RIA from Peninsula Labs. (cat. no. RIAS9086), a nonextraction IRMA from Shionogi (Shionoria® BNP), and an extraction RIA from Phoenix Pharmaceuticals (cat. no. RK-011–03). For the last assay, plasma was extracted on C18 Sep-Pak (Waters) cartridges. Protocols and manufacturers' directions were followed for all immunoassays. Plasma volumes for the determinations by the three methods were 0.1, 0.1, and 1 mL, respectively. The procedures followed were in accordance with the current revision of the Helsinki Declaration of 1975.
Figure 1
displays the agreement between each of the three immunoassays
evaluated, according to the representation of Bland and Altman
(5). There was a good agreement between the two
nonextraction immunoassays, though with a zero-bias (difference =
-97 ± 128 ng/L, mean ± 2 SD). Conversely, there was a
significant divergence between either nonextraction immunoassay and the
assay utilizing extraction, the difference increasing with the average
BNP concentration. The extraction immunoassay gave lower BNP
concentrations, on average, than either nonextraction method.
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All three immunoassays showed a good clinical correlation with left ventricular ejection fraction for the patients with CHF. After log-transformation of BNP concentrations (y values), the regression analysis resulted in the following respective parameters for the Shionogi, Peninsula, and Phoenix immunoassays: slope -0.042 ± 0.01, -0.026 ± 0.01, and -0.024 ± 0.01; intercept 3.91 ± 0.22, 3.50 ± 0.13, and 2.99 ± 0.11; and r2 0.73, 0.75, and 0.74.
In conclusion, the three immunoassays evaluated here showed similar correlations with left ventricular function in patients with CHF (r = 0.73–0.75), but the results of the two nonextraction methods differed from the results of the extraction method.
Acknowledgments
S.M. is a fellow of the "Training and Mobility of Researchers" program from the EU.
Footnotes
References
The following articles in journals at HighWire Press have cited this article:
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  F. Boomsma and A. H. van den Meiracker Plasma A- and B-type natriuretic peptides: physiology, methodology and clinical use Cardiovasc Res, August 15, 2001; 51(3): 442 - 449. [Full Text] [PDF]
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