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Original research article
Provocative biomarker stress test: stress-delta N-terminal pro-B type natriuretic peptide
  1. Alexander T Limkakeng Jr1,
  2. J Clancy Leahy1,
  3. S Michelle Griffin1,
  4. Yuliya Lokhnygina2,
  5. Elias Jaffa1,
  6. Robert H Christenson3 and
  7. L Kristin Newby4
  1. 1 Division of Emergency Medicine, Duke University School of Medicine, Durham, North Carolina, USA
  2. 2 Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA
  3. 3 Department of Pathology, University of Maryland School of Medicine, Baltimore, USA
  4. 4 Division of Cardiology, Department of Medicine, Duke Clinical Research Institute, Durham, North Carolina, USA
  1. Correspondence to Alexander T Limkakeng Jr; alexander.limkakeng{at}


Objective Stress testing is commonly performed in emergency department (ED) patients with suspected acute coronary syndrome (ACS). We hypothesised that changes in N-terminal pro-B type natriuretic peptide (NT-proBNP) concentrations from baseline to post-stress testing (stress-delta values) differentiate patients with ischaemic stress tests from controls.

Methods We prospectively enrolled 320 adult patients with suspected ACS in an ED-based observation unit who were undergoing exercise stress echocardiography. We measured plasma NT-proBNP concentrations at baseline and at 2 and 4  hours post-stress and compared stress-delta NT-proBNP between patients with abnormal stress tests versus controls using non-parametric statistics (Wilcoxon test) due to skew. We calculated the diagnostic test characteristics of stress-delta NT-proBNP for myocardial ischaemia on imaging.

Results Among 320 participants, the median age was 51 (IQR 44–59) years, 147 (45.9%) were men, and 122 (38.1%) were African–American. Twenty-six (8.1%) had myocardial ischaemia. Static and stress-deltas NT-proBNP differed at all time points between groups. The median stress-deltas at 2  hours were 10.4 (IQR 6.0–51.7) ng/L vs 1.7 (IQR −0.4 to 8.7) ng/L, and at 4  hours were 14.8 (IQR 5.0–22.3) ng/L vs 1.0 (−2.0 to 10.3) ng/L for patients with ischaemia versus those without. Areas under the receiver operating curves were 0.716 and 0.719 for 2-hour and 4-hour stress-deltas, respectively. After adjusting for baseline NT-proBNP levels, the 4-hour stress-delta NT-proBNP remained significantly different between the groups (p=0.009).

Conclusion Among patients with ischaemic stress tests, static and 4-hour stress-delta NT-proBNP values were significantly higher. Further study is needed to determine if stress-delta NT-proBNP is a useful adjunct to stress testing.

  • echocardiography
  • emergency medicine
  • coronary artery disease
  • acute coronary syndrome
  • myocardial ischaemia and infarction (IHD)
  • biomarkers

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  • Contributors ATL conceived the study. ATL, LKN and YL designed the analysis. ATL and LKN obtained funding for the project. ATL, EJ, JCL and MG oversaw enrolment, data collection, blood specimen collection and storage. RC oversaw the analysis of blood samples and provided expertise on laboratory-related content. ATL, EJ, YL and JCL managed the data. YL provided the statistical analysis plan and analysed the data. ATL drafted the manuscript, and all authors contributed substantially to its revision. ATL takes responsibility as guarantor for the content of the paper as a whole.

  • Funding Financial support was not dependent on the results of the study. Roche Diagnostics International provided salary support for investigators and materials for testing samples. The investigators retained control of the data throughout the study and the decision of whether to publish the results. The Duke Office of Clinical Research’s support of this project was made possible by Grant Number 1 UL1 RR024128-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and the NIH Roadmap for Medical Research. Its content is solely the responsibility of the authors and does not necessarily represent the official view of the NCRR or the NIH.

  • Competing interests ATL would like to disclose that he has received research support from Roche Diagnostics, Siemens Healthcare Diagnostics and Abbott Laboratories, all of which are manufacturers of troponin and B-type natriuretic peptide assays. RHC has served as a consultant and member of scientific advisory groups for Roche Diagnostics, Quidel Diagnostics, Beckman Coulter Diagnostics, and Siemens Healthcare Diagnostics. LKN reports receiving consulting honoraria from Roche Diagnostics and Philips Healthcare, which produce products related to the current research, and from AstraZeneca HCF, Metanomics and Medscape. She has received research grants from Bristol-Myers Squibb, GlaxoSmithKline, Google Life Sciences (Verily), NHLBI and the MURDOCK Study.

  • Patient consent Not required.

  • Ethics approval The Duke University Medical Center Institutional Review Board approved this protocol.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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