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NT-proBNP Medical Background

	Overview Medical Background Literature

Medical Background

Source & biological action

The heart not only has a pumping function but is also an endocrine gland. Especially well-known are two peptides that are released from the myocardium into the circulation upon myocardial stress: Atrial natriuretic peptide (ANP) and BNP. Whereas ANP is mainly released from the atrium, BNP is mainly released from the ventricle. Both natriuretic peptides are key regulators in the homeostasis of salt and water excretion and in the maintenance of blood pressure.

BNP is synthesized as a prohormone called proBNP. After stimulation of the cardiomyocytes, proBNP is cleaved by a protease into N-terminal proBNP (NT-proBNP) and the biologically active hormone BNP. The biological half-life of NT-proBNP is 60 - 120 minutes and thus higher than BNP which is only 20 minutes.

Indications for testing

• Diagnosis of congestive heart failure in symptomatic patients
• Discrimination between cardiac and non cardiac dyspnea and exclusion of the diagnosis heart failure
• Assessment of prognosis in patients with heart failure
• Risk stratification and assessment of prognosis in acute coronary syndrome
• Monitoring of heart failure patients for tailoring treatment and improving patient outcome

Patient preparation

No special preparation required

Results

Determination

Testing for NT-proBNP can be done directly in your office or in the lab. Roche Diagnostics offers you both: Roche Cardiac proBNP, a point-of-care NT-proBNP test done in heparinized whole blood with the Roche Cardiac reader, the cobas h 232 system or a lab test done in plasma or serum with the Elecsys^® proBNP immunoassay from Roche Diagnostics. The test - regardless on which assay performed - add valuable information regarding both diagnosis and prognosis across a wide range of cardiovascular syndromes in primary care medicine.

Results

Reference range

For the evaluation of the reference range, NT-proBNP concentrations were determined in blood samples of approx. 2,000 donors.

According to study results, NT-proBNP values below 125 pg/ml are considered as normal. NT-proBNP values may differ between women and men and NT-proBNP values increase upon aging. However, a cut-off value of 125 pg/ml is adequate for clinical and diagnostic purposes. If NT-proBNP concentrations are below 125 pg/ml, cardiac dysfunction can be excluded with high probability, a conclusion which can also be drawn in patients presenting with dyspnea.

NT-pro BNP values above 125 pg/ml may indicate the presence of early cardiac dysfunction and are associated with an increased risk of cardiac events such as myocardial infarction, heart failure, or death.

If sex-specific differentiation of NT-proBNP is required, concentrations of 100 pg/ml and 150 pg/ml for men and women, respectively, can be considered as exclusion values.

Classification of NT-proBNP in donors according to age and sex
Age (years)	18-49	18-49	18-29	18-29
Sex	Males	Females	Males	Females
N	964	574	278	232
Median	20.0	39.3	20.0	37.0
95th percentile	63.9	125	48.8	114
95.7th percentile	84.2	146	64.7	130

Classification of NT-proBNP in donors according to age and sex
Age (years)	30-39	30-39	40-49	40-49
Sex	Males	Females	Males	Females
N	379	194	307	148
Median	20.0	36.9	20.0	49.8
95th percentile	70.7	119	64.0	146
95.7th percentile	88.1	132	94.6	231

Classification of NT-proBNP in donors according to age and sex
Age (years)	50-59	50-59	>60	>60
Sex	Males	Females	Males	Females
N	211	94	110	28
Median	27.4	65.8	42.0	61.4
95th percentile	125	186	194	204
95.7th percentile	179	270	278	262

NT-proBNP levels in patients with reduced left ventricular function
	Median
Normal (n = 1,291)	56 pg/ml
NYHA I (n = 182)	342 pg/ml
NYHA II (n = 250)	951 pg/ml
NYHA III (n = 234)	1,571 pg/ml
NYHA IV (n = 35)	1,707 pg/ml

NHYA, News York Heart Association Classification NT-proBNP is very stable in blood samples and shows nearly no diurnal variation. Therefore, quantification of NT-proBNP provides reliable and reproducible clinical information under routine conditions.

Clinical aspects

Conditions with elevated NT-proBNP

Elevated NT-proBNP levels indicate the presence of an underlying cardiac disorder:

• Heart failure and ventricular dysfunction: NT-proBNP levels correlate with disease severity and prognosis.
• Cardiovascular diseases, particularly acute coronary syndrome:
• NT-proBNP levels predict risk of death in patients who had myocardial infarction or unstable angina.
• NT-proBNP levels predict the risk of new or progressing heart failure and new or recurrent myocardial infarction.

According to guidelines of the European Society of Cardiology (ESC), due to its high diagnostic sensitivity and high negative predictive value (> 97 %) the measurement of NT-proBNP is suitable for the exclusion of patients that do not require further cardiac assessment. As a consequence, patients with elevated NT-proBNP values may be identified as candidates who require further cardiac assessment.

Tips & recommendations

• In patients who present with acute dyspnea of uncertain etiology in your office, low NT-proBNP levels (cut-off 125 pg/ml) argue for a lower risk of acute heart failure.
• NT-proBNP may be used for further risk stratification in patients with acute coronary syndrome. In order to diagnose or exclude myocardial infarction the following sequence has proven to be effective: ECG, troponin T test, determination of NT-proBNP. Patients who do not show ST-segment elevation, whose troponin T test is negative upon admission and after 6 hours, and who have a negative NT-proBNP are at low risk for cardiovascular events.
• Adjustment or change of therapy for heart failure according to serial measurements of NT-proBNP promises to improve outcomes in comparison with adjusting therapy according to unassisted clinical acumen. Thus, by monitoring therapy according to NT-proBNP levels, you can reduce the number of hospital admissions and the risk of acute congestive heart failure.

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