Download PX810501_NT-proBNP-27May2015

N-terminal-pro-brain natriuretic peptide (NT-proBNP)
Date of SC final approval
About the Measure
Domain:
Measure:
Definition:
Purpose:
Sickle Cell Disease: Cardiovascular, Pulmonary, and Renal
N-terminal pro-brain natriuretic peptide (NT-proBNP)
A bioassay to determine an individual’s level of N-terminal pro-brain natriuretic peptide
(NT-proBNP).
N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is released from the right or left
ventricle of the heart when it is under increased strain related to volume or pressure
overload. Levels of NT-pro-BNP can be used as a screening tool to evaluate an
individual’s left and right ventricular function. Elevated NT-pro-BNP levels can be used
diagnostically in decompensated congestive heart failure and they can be followed
longitudinally to understand response to therapy. In patients with pulmonary
hypertension and acute pulmonary embolism, elevated levels reflect an increased risk
of morbidity and mortality. Additionally, in patients with sickle cell disease, levels of
NT-proBNP levels > 160 pg/ml predict increased mortality risk
About the Protocol
Description of
Protocol:
Selection
Rationale:
Specific
Instructions:
This protocol provides instructions for drawing, processing, and storing blood
according to the National Health and Nutrition Examination Survey (NHANES)
methods. Because there are many comparable assays for ascertaining levels of Nterminal-pro-brain natriuretic peptide (NT-proBNP), the protocol also provides basic
guidelines to aid comparability among different studies.
The Sickle Cell Disease Cardiovascular, Pulmonary, and Renal Working Group
selected N-terminal-pro-brain natriuretic peptide (NT-proBNP) measurement because
it is a validated, specific, low-burden, and non-invasive alternative to
echocardiography for differentiating patients with ventricular dysfunction. Additionally,
this assay does not require sample extraction and there is no detectable cross
reactivity with atrial natriuretic peptide (ANP), N-terminal pro-atrial natriuretic peptide
(NT-proANP), brain natriuretic peptide (BNP), or urodilatin.
 The National Health and Nutrition Examination Survey (NHANES) instructions
for drawing, processing, and storing blood provide a standard methodology
used successfully for many years to ensure comparable results across study
sites. However, the Sickle Cell Disease Working Group 1 (Cardiovascular,
Pulmonary, and Renal) notes that certain aspects (e.g., exclusion criteria) of
the NHANES protocol are study specific and might not be applicable to all
types of studies (e.g., sickle cell disease).

N-terminal-pro-brain natriuretic peptide (NT-proBNP) analysis is performed by
plasma assay.
Protocol Text:
Summary of the N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Assay
The following is a summary version of the full National Health and Nutrition
Examination Survey 2011-2012 protocol.
Exclusion Criteria
Persons will be excluded from this component if they:
Version 10 – 10/21/09
N-terminal-pro-brain natriuretic peptide (NT-proBNP)
Date of SC final approval
• Report that they have hemophilia; or
• Report that they have received cancer chemotherapy in the last 4 weeks
SP = Sample Person.
1. Do you have hemophilia?
1[]
2[]
7[]
9[]
Yes
No
Refused
Don’t Know
If the SP answers "Yes," the SP is excluded from the blood draw.
If SP answers "No" or "Don’t Know," blood is drawn from the SP.
2. Have you received cancer chemotherapy in the past four weeks or do you
anticipate such therapy in the next four weeks?
1 [ ] Yes
2 [ ] No
7 [ ] Refused
9 [ ] Don’t Know
If the SP answers "Yes," the SP is excluded from the blood draw.
If SP answers "No" or "Don’t Know," blood is drawn from the SP.
Venipuncture Procedures
Editor’s Note: Please review chapter 4 of the Laboratory Procedures Manual from the
2011-2012 National Health and Nutrition Examination Survey (NHANES) for a full
description of phlebotomy procedures. This manual is posted here, and is also
available at the NHANES website: 2011-2012 NHANES Laboratory Procedures
Manual
Venipuncture should generally be performed using the median cubital, cephalic, or
basilic veins in the left arm unless this arm is unsuitable. If the veins in the left arm are
unsuitable, look for suitable veins on the right arm. If the veins in the antecubital
space on both arms are not suitable, then look for veins in the forearm or dorsal side
of the hand on the left arm/hand and then the right arm/hand.
Recording the Results of the Venipuncture Procedure
Immediately after completing the venipuncture, record the results of the blood draw,
the reasons for a tube not being drawn according to the protocol, and any comments
about the venipuncture.
Blood Processing
Please review chapter 8 of the Laboratory Procedures Manual from the National
Version 10 – 10/21/09
N-terminal-pro-brain natriuretic peptide (NT-proBNP)
Date of SC final approval
Health and Nutrition Examination Survey 2011-2012 for a full description of blood
processing procedures: 2011-2012 NHANES Laboratory Procedures Manual
•
•
Centrifuge the tube at room temperature to separate the plasma and aliquot
into an appropriate storage tube.
Determine if the plasma is hemolyzed, turbid, lipemic, or icteric. If so, enter a
comment to describe the plasma.
Laboratory Assay for NT-proBNP
NT-proBNP can be measured using a two-step sandwich enzyme-linked
immunosorbent assay (ELISA) in streptavidin-coated microtitre plates. The Sickle Cell
Disease Working Group 1 (Cardiovascular, Pulmonary, and Renal) notes that there
are a number of different reagents and instruments that are appropriate to measure
the concentration of NT-proBNP. Once an assay is chosen for a particular study, the
Working Group recommends that no changes in the protocol be made over the course
of the study. To aid comparability, the Working Group recommends that the
investigator record the make and manufacturer of equipment used and the
repeatability and coefficients of variation for the assay.
Reference Ranges
Participant:
Source:
Language of
Source:
Personnel and
Training Required:
Equipment Needs:
Protocol Type:
Age
< 50 years old
50-75 years old
>75 years old
Adults
Range (pg/mL)
300 - 450
300 - 900
300 – 1800
Centers for Disease Control and Prevention (CDC). (2011). National Health and
Nutrition Examination Survey Questionnaire, Laboratory Procedures Manual.
Hyattsville, MD: U.S. Department of Health and Human Services, Centers for Disease
Control and Prevention.
Bay, M., Kirk, V., Parner, J., Hassager, C., Nielsen, H., Krogsgaard, K., Trawinski, J.,
Boesgaard, S., & Aldershvile, J. (2003). NT-proBNP: A new diagnostic screening tool
to differentiate between patients with normal and reduced left ventricular systolic
function. Heart, 89, 150–154.
English
A phlebotomist, nursing staff, or other health care professional who is trained to draw
blood and laboratory staff who are trained to perform this assay.
Phlebotomy supplies, centrifuge for serum separation, and freezer for sample storage
is required.
Bioassay
Requirements:
Requirements Category
Major equipment
Required (Yes/No):
No
Version 10 – 10/21/09
N-terminal-pro-brain natriuretic peptide (NT-proBNP)
Date of SC final approval
Common Data
Elements:
General
References:
Specialized training
No
Specialized requirements for biospecimen
collection
Average time of greater than 15 minutes in an
unaffected individual
TBD by PhenX Team
No
No
Machado, R. F., Hildesheim, M., Mendelsohn, L., Remaley, A. T., Kato, G. J., &
Gladwin, M. T. (2011). NT-pro brain natriuretic peptide levels and the risk of death in
the cooperative study of sickle cell disease. British Journal of Haematology, 154(4),
512-520.
Machado, R. F., Anthi, A., Steinberg, M. H., Bonds, D., Sachdev, V., Kato, G. J.,
Taveira-DaSilva, A. M., Ballas, S. K., Blackwelder, W., Xu, X., Hunter, L., Barton, B.,
Waclawiw, M., Castro,O., Gladwin, M. T., & MSH Investigators. (2006). N-Terminal
Pro-Brain Natriuretic Peptide Levels and Risk of Death in Sickle Cell Disease. JAMA,
296(3), 310-318. doi:10.1001/jama.296.3.310
Karl, J., Borgya, A., Gallusser, A., Huber, E., Krueger, K., Rollinger, W. & Schenk, J.
(1999). Development of a novel, N-terminal-proBNP (NT-proBNP) assay with a low
detection limit. Scandinavian Journal of Clinical and Laboratory Investigation,
59(Suppl230), 177-181.
Tamizifar, B., & Rismankarzadeh, M. (2012). Using NT-proBNP as a criterion for heart
failure hospitalization. Journal of Research in Medical Sciences, 17(1): 111-113.
Pfister, R., & Schneider, C. A. (2008). ESC guidelines for the diagnosis and treatment
of acute and chronic heart failure 2008: application of natriuretic peptides. European
Heart Journal, 382-383. doi: http://dx.doi.org/10.1093/eurheartj/ehn560 382-383
Additional Information About the Measure
Essential Data:
Current Age, Race, Ethnicity
Related PhenX
Measures:
Derived Variables:
Keywords/Related
Concepts:
Heart Valve Function, Pulmonary Hypertension, Blood Pressure
None
N-terminal pro-brain natriuretic peptide, NT-proBNP, left ventricular ejection fraction,
LVEF, sickle cell disease, SCD, chronic heart failure, pulmonary hypertension, PH,
biomarkers, immunoassay
Version 10 – 10/21/09