NT-proBNP

What is a NT-proBNP test?

A B-type natriuretic peptide (BNP) test gives you information about how your heart is working. This blood test measures the levels of a protein called BNP in your bloodstream. 

→ When your heart has to work harder to pump blood, it makes more BNP. Higher levels of BNP can be a sign of heart failure.

Natriuretic peptide tests measure the levels of BNP or NT-proBNP in your blood. Your health care provider may order a BNP test or an NT-proBNP test, but not both. They are both useful in diagnosing heart failure, but rely on different types of measurements. The choice will depend on the equipment available in your provider's recommended laboratory.

If you already know you have heart failure, your provider may order this test to check the severity (seriousness) of your condition. They may also use this test to monitor how heart failure treatments are working. In some cases, your provider may also order it if they think you may be at higher risk of developing heart failure.

If you've already been diagnosed with heart failure, the test may be used to:

→ Find out the severity of the condition

→ Plan treatment

→ Find out if treatment is working

→ The test may also be used to find out whether or not your symptoms are due to heart failure.

What is BNP?

Both BNP and NT-proBNP are markers of atrial and ventricular distension due to increased intracardiac pressure.

BNP is one of several proteins that help regulate blood circulation throughout your body. Even though your heart makes this protein, providers sometimes call it “brain” natriuretic peptide because it was first discovered in brain tissue.

As part of your circulatory system, your heart and blood vessels pump oxygen-rich blood to your muscles, organs and other tissues. The left ventricle (one of the heart’s four chambers) pumps a great deal of blood through the heart and it goes on to flow through your body.

The left ventricle is one of the main organs that make BNP. As your heart stretches due to increasing load or experiences increased stress from injury, BNP levels rise. Your heart muscle cells respond to such stress by secreting BNP to unload your heart, which prompts your kidneys to relieve salt and water (hence the name “natriuretic”).

What are natriuretic peptides?

Natriuretic peptides are substances made by the heart. Two main types of these substances are brain natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP). 

Normally, only small levels of BNP and NT-proBNP are found in the bloodstream. High levels can mean your heart isn't pumping as much blood as your body needs. When this happens, it's known as heart failure, sometimes called congestive heart failure.

What is the main purpose of the NT-proBNP test?

The main purpose of BNP or NT-proBNP testing is to see if the blood levels of these proteins are within the expected range for a healthy person. These tests are most commonly used for diagnosis but may be involved in other health assessments.

BNP and NT-proBNP testing may also be used to evaluate people who have already been diagnosed with congestive heart failure. In these patients, testing may be ordered to assess the severity of the disease and its likely course or prognosis. Less often, BNP or NT-proBNP tests may be considered when determining what type of treatment to prescribe or when monitoring a patient’s health over time.

What is a diagnosis?

Diagnosis is the process of finding the underlying cause of symptoms. BNP and NT-proBNP tests are often used to determine if a patient has heart failure. Heart failure is a condition in which the heart is not pumping blood properly to the rest of the body, but it does not mean that the heart has stopped.

What are possible symptoms of congestive heart failure?

Heart failure means your heart isn’t pumping blood as it should. It doesn’t mean that your heart has failed or stopped working entirely.

People with congestive heart failure may experience various symptoms, including swelling and shortness of breath. However, these symptoms can be caused by many other conditions besides heart failure. BNP and NT-proBNP testing can be used to help find out if heart failure or some other condition is the cause of a patient’s symptoms.

Shortness of breath is extremely common among people who have congestive heart failure, but this symptom can also occur in other conditions such as lung, kidney, and liver disease. For this reason, your doctor is likely to order a BNP or NT-proBNP test if you have unexplained shortness of breath.

Some possible symptoms of heart failure:

→ Difficulty breathing, shortness of breath (dyspnea) or wheezing

→ Swelling (edema) in your abdomen, legs, ankles and feet

→ Cough that seems dry or “hacking” and gets worse when laying down

→ Delirium (confusion)

→ Dizziness or fainting (syncope)

→ Fatigue or feeling sluggish

→ Heart palpitations

→ Nausea and vomiting or loss of appetite.

→ Urinating (peeing) more than usual at night (nocturia).

Get emergency medical help if you have these symptoms. Heart failure is life-threatening and requires immediate treatment.

If your provider has already diagnosed you with heart failure, they may order a BNP or NT-proBNP test to monitor how treatments are working.

What does the test NT-proBNP measure exactly?

These tests measure blood levels of BNP or NT-proBNP, which are proteins that are made by the heart and blood vessels. These hormones are secreted into the bloodstream in response to excess fluid accumulating in the blood vessels. The active hormone, BNP, encourages the removal of water and salt from the blood.

When should I get a BNP or NT-proBNP test?

Your doctor may order a BNP or NT-proBNP test if you have symptoms of heart failure. If you have already been diagnosed with heart failure, your doctor might order a test to get more information about your condition.

What are normal results for NT-proBNP and BNP?

For people who don’t have heart failure, normal BNP levels are less than 100 picograms per milliliter (pg/mL). BNP levels over 100 pg/mL may be a sign of heart failure.

For NT-proBNP, normal levels are less than 125 pg/mL for people under 75 years old and less than 450 pg/mL for people over age 75. NT-proBNP levels over 900 pg/mL may be a sign of heart failure.

Every person has their own range of BNP or NT-proBNP level range. Ask your provider about the specific measurements of your BNP test or NT-proBNP test.

Heart failure medications, including beta blockers, ACE inhibitors and diuretics, can lower BNP or NT-proBNP levels in the blood. If you’re taking these drugs to treat heart failure, your BNP or NT-proBNP test results may be lower than if you’re not taking them. Your levels can also be lower if you have obesity or kidney failure.

Depending on the results of the BNP test, your provider may order follow-up tests, such as an electrocardiogram (EKG or ECG). This test monitors your heart rate through sensors attached to your skin. It can help your provider diagnose or evaluate heart failure and other heart problems.

If your BNP or NT-proBNP results were normal, it probably means your symptoms are not being caused by heart failure. Your provider may order more tests to help make a diagnosis.

Your health care provider may order one or more of the following tests in addition to or after you've had a BNP or NT-proBNP test:

→ Electrocardiogram, which looks at heart's electrical activity

→ Stress test, which shows how well your heart handles physical activity

→ Chest x-ray to see if your heart is larger than normal or if you have fluid in your lungs

You may also get one or more of the following blood tests:

→ ANP test. ANP stands for atrial natriuretic peptide. ANP is similar to BNP but it is made in a different part of the heart.

→ Metabolic panel to check for kidney disease, which has similar symptoms to heart failure

→ Complete blood count to check for anemia or other blood disorders

Reference values:

Under 50 years of age:

N-terminal pro brain natriuretic peptide (NT-proBNP) values below 300 pg/mL have a 99% negative predictive value for excluding acute congestive heart failure (CHF). A cutoff of 1200 pg/mL for patients with an estimated glomerular filtration rate (eGFR) below 60 yields a diagnostic sensitivity and specificity of 89% and 72% for acute CHF. NT-proBNP values greater than 450 pg/mL are consistent with CHF in adults under 50 years of age.

50-75 years of age:

NT-proBNP values below 300 pg/mL have a 99% negative predictive value for excluding acute CHF. A cutoff of 1200 pg/mL, for patients with an eGFR below 60 yields a diagnostic sensitivity and specificity of 89% and 72% for acute CHF. A diagnostic NT-proBNP cutoff of 900 pg/mL has been suggested in adults 50 to 75 years of age in the absence of renal failure.

Over 75 years of age:

NT-proBNP values below 300 pg/mL have a 99% negative predictive value for excluding acute CHF. A cutoff of 1200 pg/mL for patients with an eGFR below 60 yields a diagnostic sensitivity and specificity of 89% and 72% for acute CHF. A diagnostic NT-proBNP cutoff of 1800 pg/mL has been suggested in adults over 75 years of age in the absence of renal failure.

What is Congestive Heart Failure:

With nearly 500,000 new cases per year and direct costs estimated as high as US$38 billion annually, congestive heart failure (CHF) has become a major priority in modern medicine. This crisis will continue to grow as the population ages, thus the discernment of new diagnostic and therapeutic strategies to improve prognosis and reduce costs is critical.

Therapies and NT-proBNP as an early diagnostic tools:

The irony is that therapies with great benefit for patients with CHF exist, such as angiotensin converting enzyme (ACE) inhibitors and beta-blockers. However, these agents are under-utilized, and when employed may be dosed inadequately. Accordingly, a widely available and accurate diagnostic tool to identify those with CHF would be essential in order to identify those patients eligible for proven therapies in CHF. Such a diagnostic tool for early diagnosis would theoretically lead to earlier initiation of these beneficial medicines while potentially assisting in chronic out-patient management of such patients. As CHF is the leading cause of hospitalization in adults over 65, achieving such early diagnosis and initiation of therapy would thus prevent hospitalizations and reduce the considerable costs of CHF.

Markers of cardiac neurohormonal activation, particularly B-type natriuretic peptides, have been identified as possible tools to identify and treat patients with CHF. While most studies to date have focused on the diagnostic utility of B-type natriuretic peptide (BNP), more recent research has revealed that the amino-terminal fragment of the BNP molecule (NT-proBNP), a marker with great diagnostic and prognostic power, is a marker for CHF. 

The natriuretic peptides are a family of molecules consisting of several structurally-related hormones. At present, the natriuretic peptide family includes atrial natriuretic peptide (ANP), B-type (or brain) natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and dendroaspis natriuretic peptide (DNP).

In particular, the B-type natriuretic peptide family has gained popularity as candidate markers for CHF. Biologically, these neurohormones affect body fluid homeostasis (through natriuresis and diuresis) and vascular tone (through decreased angiotensin II, norepinephrine synthesis), both essential components in the pathophysiology of CHF.

The difference between BNP and NT-proBNP:

Although derived from a common precursor, BNP and NT-proBNP are considerably different in many ways. As a biologically active compound, BNP is actively cleared from the circulation via natriuretic peptide receptors, as well as by degradation by neutral endopeptidases in the bloodstream. Accordingly, the half-life of BNP is only 18 minutes. Additionally, once drawn, BNP levels are not stable in vitro for long periods, dropping significantly over the first 24 hours following collection. 

Also, if blood is collected into glass tubes, BNP levels may fall, due to activation of the kallikrein system. NT-proBNP is not biologically active, and as such does not have active clearance mechanisms. Therefore, the half-life of NT-proBNP is approximately 60-120 minutes. In humans, a renal route of clearance is suspected as a partial mechanism for NT-proBNP metabolism. NT-proBNP is dramatically more stable than BNP, with very little variation in the level of the marker after collection for at least 72 hours, and probably longer. In addition, NT-proBNP may be collected into glass tubes without any issues.

As noted above, sensitive assays now exist for both markers, though the NT-proBNP assay may be more sensitive than BNP in certain scenarios. Recent data has grown demonstrating the value of NT-proBNP testing for a wide variety of uses for patients with CHF.

Uses of NT-proBNP in CHF:

A significant body of evidence has developed to demonstrate that NT-proBNP levels correlate with diagnosis, clinical status and prognosis in congestive heart failure, and may be useful for the longitudinal management of patients with CHF.

Management of CHF:

NT-proBNP is clearly useful for diagnosis and prognosis of CHF, and may be useful for monitoring and guiding therapy to improve such potential risk. 

Other Uses of NT-proBNP:

While much of the literature has focused on the natriuretic peptides in CHF, it is necessary to point out that NT-proBNP may be elevated in states other than CHF, such as acute coronary syndromes (ACS) as well as pulmonary thromboembolism (PE).

Similar to CHF, ACS patients constitute a large, high-risk population, for which an early diagnostic and prognostic marker would prove useful. Multiple studies of patients with ACS now demonstrate that NT-proBNP levels are the most powerful predictor of mortality at presentation, superior to troponins for this purpose.

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Other links referenced:

https://www.aafp.org/pubs/afp/issues/2006/1201/p1893.html

https://www.heart.org/en/health-topics/heart-failure/diagnosing-heart-failure

https://www.aafp.org/afp/2006/1201/p1893.html

https://my.clevelandclinic.org/health/diagnostics/16814-nt-prob-type-natriuretic-peptide-bnp

https://labtestsonline.org/tests/bnp-and-nt-probnp

https://labtestsonline.org/conditions/congestive-heart-failure

https://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/heart-disease/art-20049357

https://www.nhlbi.nih.gov/health/blood-tests

https://ufhealth.org/conditions-and-treatments/brain-natriuretic-peptide-test

https://ufhealth.org/conditions-and-treatments/exercise-stress-test

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https://www.uscjournal.com/articles/nt-probnp-new-test-diagnosis-prognosis-and-management-congestive-heart-failure

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