NT-proBNP

NT-proBNP (N-terminal pro-BNP; N-terminal pro brain natriuretic peptide) and brain natriuretic peptide (BNP; B-natriuretic peptide, B-type natriuretic peptide) are cardiac peptide hormones produced in the heart when a precursor (pro BNP) is cleaved. NT-pro BNP is formed in the left ventricle and BNP is formed mainly in the atria (less formation in the ventricles). In addition to BNP, natriuretic peptides include ANP (atrial natriuretic peptide) and CNP (c-type natriuretic peptide). The trigger for BNP release is the stretching of the myocardium (heart muscle) during hemodynamic overload of the heart in heart failure (cardiac insufficiency). BNP has a vasodilatory (“vasodilating”) effect and inhibits the activated renin-angiotensin-aldosterone system (RAAS), which regulates the body’s fluid and electrolyte balance and thus has a critical effect on blood pressure. NT-pro BNP is eliminated exclusively renally, and has a significantly longer plasma half-life of 60-120 min than BNP (approx. 23 min). BNP is degraded in the kidney, lung, heart, and vascular endothelia, and is also eliminated renally. NT-pro BNP reflects hemodynamic changes over a longer period of time than BNP (NT-pro BNP approximately 12 h; BNP approximately 2 h). Because of better sample stability (in serum 72 h at room temperature) and the previously mentioned facts, NT-proBNP should be determined.

Procedure

Material needed

Preparation of the patient

  • Blood collection should be performed on the fasting patient or after a light breakfast, if possible.
  • Blood collection only in physical rest; no physical stress in the last hours before collection.

Interfering factors

  • Not known

Standard values

Parameter Women Men
NT-proBNP*
  • <155 pg/ml* * (<50 years)
  • < 222 pg/ml* * (50-65 years)
  • < 84 pg/ml* * (< 50 years)
  • < 194 pg/ml* * (50-65 years)
ESC guidelines: <300 pg/ml
BNP
  • <150 pg/ml
  • <100 pg/ml
ESC guidelines: < 100 pg/ml

* Note: Values in EDTA plasma are approximately10% lower. * * Conversion factor NT-proBNP

  • Pg/ml x 0.118 = pmol/l
  • Pmol/l x 8.457 = pg/ml

Indications

  • Heart failure
    • Exclusion/diagnosis and therapy monitoring
    • Determination of the severity of cardiac functional impairment (BNP or NT-proBNP are increased proportionally to the severity of functional impairment).
    • Acute myocardial infarction (heart attack) → heart failure due to necrosis (tissue death) or remodeling?
    • Unstable angina pectoris (one speaks of an unstable angina pectoris / chest tightness or heart pain, if the complaints have increased in intensity or duration compared to the previous angina pectoris attacks) → heart failure due to damage to the myocardium (heart muscle tissue)?
    • Dilated cardiomyopathy (DCM; abnormal dilation (dilatation) of the heart muscle, especially the left ventricle) → heart failure?
  • Differential diagnosis of cardiac (heart-related) and pulmonary (lung-related) dyspnea (shortness of breath).

Interpretation

Interpretation of increased values

  • Acute coronary syndrome (ACS) – spectrum of cardiovascular disease caused by occlusion or high-grade stenosis of a coronary artery.
  • Arterial hypertension (high blood pressure).
  • Atrial and ventricular arrhythmia (cardiac arrhythmias originating in the atrium and ventricle), e.g., atrial fibrillation (VHF); elevation even with normal left ventricular function
  • Heart failure (cardiac insufficiency).
  • Valvular heart disease/valvular heart disease (e.g. mitral regurgitation)
  • Cardiac contusion (cardiac contusion)
  • Hypertension (high blood pressure) with left ventricular hypertrophy (LVH; left ventricular hypertrophy).
  • Congenital heart disease (congenital heart disease).
  • Left ventricular dysfunction – malfunction of the left ventricle.
  • Myocarditis (inflammation of the heart muscle)
  • Restrictive cardiomyopathy – heart muscle disease associated with thickening of the innermost heart wall (endocardium) and leading to fibrosis (increased deposits of connective tissue, scarring) of the heart muscle.
  • Noncardiac causes (noncardiac causes):
    • Anemia (anemia of the blood)
    • Diabetes mellitus
    • Hyperthyroidism (overactive thyroid gland)
    • Liver failure – dysfunction of the liver with partial or complete failure of its metabolic functions.
    • Liver cirrhosis – connective tissue remodeling of the liver leading to functional limitations.
    • Pulmonary embolism – partial (partial) or complete obstruction of a pulmonary artery, mainly due to pelvic-leg thrombosis (about 90% of cases).
    • Neurological disorders (e.g., subarachnoid hemorrhage (SAB), intracerebral hemorrhage (ICB)).
    • Renal insufficiency – process leading to a slowly progressive reduction in renal function.
    • Paraneoplastic syndromes – concomitant symptoms of cancer that do not arise primarily from the neoplasm (solid tumors or leukemias).
    • Pulmonary hypertension (PH) – pressure increase in the pulmonary artery system (here also prognostic parameter).
    • Physiological during physical exertion (increase about 1 h).
    • Severe burns
    • Severe metabolic (metabolic) disorders.
    • Advanced age
  • Other: cardioversion, defibrillation, cardiac surgery.
Classification Clinic NT-proBNF (pg/ml), median SD*
NYHA I(asymptomatic) Absence of symptoms at rest 341 pg/ml 40,3
NYHA II(mild) Impaired exercise capacity with greater physical exertion 951 pg/ml 112,4
NYHA III(moderate) Marked limitation of performance even with low exertion, but no discomfort at rest 1571 pg/ml 185,7
NYHA IV(severe) Complaints already at rest(resting insufficiency) 1707 pg/ml 201,8
Exclusion of ventricular dysfunction. <125 pg/ml < 14,8

* SD (standard deviation) Interpretation of lowered values.

Not relevant to disease; occurs in, among others:

  • Obesity
  • Beta blockers (long-term)
  • ACE inhibitors
  • Angiotensin II receptor antagonists
  • Aldosterone antagonists (spironolactone, eplerone).

Other notes

  • Elevated levels have been described for women on hormone replacement therapy and in patients with renal insufficiency* and dialysis.
  • In one study, BNP levels and age were found to be the strongest predictors of mortality in both patients with and without heart failure; in patients without heart failure, BNP was even stronger as a predictor than age.

* Up to a serum creatinine of 2 mg/dl, there is no clinically relevant effect of renal function on NT-proBNP levels according to the current studies.