B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) assist in the diagnosis of heart failure (HF) and in determining patient prognosis. In response to myocardial wall stretch, pre-proBNP is synthesized and processed to proBNP; which is further processed to the biologically inactive NT-proBNP fragment and the biologically active BNP fragment. Since BNP and NT-proBNP are elevated in patients with HF, both are useful adjuncts to clinical evaluation. In fact, the seminal studies for BNP and NT-proBNP demonstrated similar sensitivity and specificity for ruling in and ruling out HF. However, measurable concentrations of NT-proBNP are higher in plasma than BNP necessitating different clinical cut-points. For example, the accepted rule out cut-points for acute HF for BNP is 100 pg/mL and for NT-proBNP is 300 pg/mL. Subsequently, clinical guidelines give no direction to clinicians or laboratorians with regards to the best natriuretic peptide to test for assessing HF (1).
Despite the widespread acknowledgement that these tests are essentially clinically equivalent, no published study had assessed diagnostic concordance between BNP and NT-proBNP for ruling in and ruling out HF at the accepted cut-points. To close this gap in the literature, we performed BNP and NT-proBNP testing on 3,029 patient samples with physician ordered BNP from our hospital. We then assigned patients to two groups: 1) those that were ordered from the ED were assigned the cut-points for acute HF and 2) those from out-patient clinics, ICU’s and hospital floors were assigned the cut-points for non-acute HF. We found that there was relatively low diagnostic concordance and correlation between BNP and NT-proBNP using the current cutoffs for HF. In other words, there were frequent occasions where patients would have been ruled out for HF by one method and ruled in for HF by the other. Moreover, we found that chronic kidney disease had a profound negative impact on concordance between the two tests (2).
What this study emphasizes are the multiple biological and analytical complexities associated with natriuretic peptide immunoassays. There are multiple, well known issues with measuring BNP and NT-proBNP in patient specimens including differences in protein glycosylation, half-lives, renal clearance, biochemical diversity in HF patients, and variable reactivity of antibodies with the precursor proBNP (3). Consequently, BNP and NT-proBNP are clearly not interchangeable. Interestingly, BNP assays are only harmonized at 100 pg/mL, complicating interpretation between different assays above and below this concentration. Therefore, different BNP assays are also not interchangeable. Accordingly, the IFCC committee on Clinical Applications of Cardiac Biomarkers recommends against using different natriuretic peptide assays in clinical practice (4). Further studies are needed to examine the diagnostic concentrations of natriuretic peptides, modes of clearance, and assay specificity for circulating forms. For laboratorians and clinicians, it is important to understand the clinical and analytic contexts of each of these methods for analyzing natriuretic peptides for HF.
- Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr., Drazner MH, et al. 2013 accf/aha guideline for the management of heart failure: A report of the american college of cardiology foundation/american heart association task force on practice guidelines. J Am Coll Cardiol 2013;62:e147-239.
- Farnsworth CW, Bailey AL, Jaffe AS, Scott MG. Diagnostic concordance between nt-probnp and bnp for suspected heart failure. Clin Biochem 2018;59:50-5.
- Vasile VC, Jaffe AS. Natriuretic peptides and analytical barriers. Clin Chem 2017;63:50-8.
- Kavsak PA, Lam CSP, Saenger AK, Jaffe AS, Collinson P, Pulkki K, et al. Educational recommendations on selected analytical and clinical aspects of natriuretic peptides with a focus on heart failure: A report from the ifcc committee on clinical applications of cardiac biomarkers. Clin Chem 2019.