Protocol - N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
- Abdominal Aortic Aneurysm
- Blood Pressure (Adult/Primary)
- Deep Venous Thrombosis
- Heart Valve Function
- Peripheral Arterial Disease
- Pulmonary Embolism
Description
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 N-terminal-pro-brain natriuretic peptide (NT-proBNP), the protocol also provides basic guidelines to aid comparability among different studies.
Specific Instructions
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). Investigators who want to include participants that have hemophilia or have received cancer chemotherapy in the last 4 weeks will need to implement special venipuncture procedures.
The Sickle Cell Disease Curative Therapies Working Group (WG) notes that the N-terminal-pro-brain natriuretic peptide (NT-proBNP) analysis can be performed on plasma or serum. Additionally, NT-proBNP is cleared by the kidneys and levels may be impacted by chronic kidney disease and renal dysfunction (Tagore et al., 2008).
Availability
Protocol
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:
- 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 [ ] 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.
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.
The sample should be collected in a red-top tube, gel-barrier tube, green-top (lithium heparin), or lavender-top (EDTA) tube.
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 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 Cardiovascular, Pulmonary, and Renal Working Group 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
| Age | Range (pg/mL) |
| < 50 years old | 300 - 450 |
| 50-75 years old | 300 - 900 |
| >75 years old | 300 - 1800 |
Personnel and Training Required
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.
Equipment Needs
Phlebotomy supplies, centrifuge for serum separation, and freezer for sample storage is required.
Requirements
| Requirement Category | Required |
|---|---|
| Major equipment | No |
| Specialized training | No |
| Specialized requirements for biospecimen collection | No |
| Average time of greater than 15 minutes in an unaffected individual | No |
Mode of Administration
Bioassay
Lifestage
Adult
Participants
Adults, ages 18 and older
Selection Rationale
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.
Language
English
Standards
| Standard | Name | ID | Source |
|---|---|---|---|
| Human Phenotype Ontology | Increased NT-proBNP level | HP:0031185 | HPO |
| Human Phenotype Ontology | Sickle Cell Anemia | ORPHA:232 | HPO |
| Human Phenotype Ontology | Anemia | OMIM:603903 | HPO |
| caDSR Form | PhenX PX810501 - Nterminal Probrain Natriuretic Peptide Ntprobnp | 6252508 | caDSR Form |
Derived Variables
None
Process and Review
Not applicable.
Protocol Name from Source
National Health and Nutrition Examination Survey Questionnaire (NHANES), Laboratory Procedures Manual, 2011
Source
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.
General References
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.
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
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.
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.
Tagore, R., Ling, L. H., Yang, H., Daw, H. Y., Chan, Y. H., & Sethi, S. K. (2008). Natriuretic peptides in chronic kidney disease. Clinical Journal of the American Society of Nephrology: CJASN, 3(6), 1644-1651.
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.
Protocol ID
810501
Variables
Export Variables| Variable Name | Variable ID | Variable Description | dbGaP Mapping | |
|---|---|---|---|---|
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Age | ||||
| PX810501030000 | Age | Variable Mapping | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Assay_Repeatability | ||||
| PX810501110000 | Repeatability of the NT-proBNP assay | N/A | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Blood_Draw_Results | ||||
| PX810501040000 | Record the results of the blood draw. | N/A | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Blood_Draw_Tube_Deviation | ||||
| PX810501050000 | Record reasons for a tube not being drawn more | N/A | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Chemotheraphy_4weeks | ||||
| PX810501020000 | Have you received cancer chemotherapy in the more | Variable Mapping | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Coefficients_Variation_Assay | ||||
| PX810501120000 | Coefficients of variation of the NT-proBNP assay | N/A | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Concentration | ||||
| PX810501080000 | NT-proBNP concentration | N/A | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Equipment_Make | ||||
| PX810501090000 | Make of the equipment used to perform the more | N/A | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Equipment_Manufacturer | ||||
| PX810501100000 | Manufacturer of the equipment used to more | N/A | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Hemophilia | ||||
| PX810501010000 | Do you have hemophilia? | Variable Mapping | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Plamsa_Description | ||||
| PX810501070200 | If plasma is hemolyzed, turbid, lipemic, or more | N/A | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Plamsa_Determination | ||||
| PX810501070100 | Determine if the plasma is hemolyzed, more | N/A | ||
| PX810501_NTerminalProBrainNatriureticPeptide_NTProBNP_Venipuncture_Comments | ||||
| PX810501060000 | Record any comments about the venipuncture. | N/A | ||
Measure Name
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Release Date
July 30, 2015
Definition
A bioassay to determine an individual’s level of N-terminal pro-brain natriuretic peptide (NT-proBNP).
Purpose
N-terminal pro-brain natriuretic peptide (NT-proBNP) 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-proBNP can be used as a screening tool to evaluate an individual’s left and right ventricular function. Elevated NT-proBNP 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.
Keywords
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, "Cardiovascular, Pulmonary, and Renal"
Measure Protocols
| Protocol ID | Protocol Name |
|---|---|
| 810501 | N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) |
Publications
There are no publications listed for this protocol.