By Dr Christopher Ting Chief General Manager, Malaysia/Singapore
Heart Failure Facts
- Prevalence of 22 Million people worldwide (as common as diabetes in the elderly) and increasing with improving survival of post myocardial infarct patients
- The cause of 400,000 deaths per year
- The most common cause of hospitalisation for those above 65 years
- Diagnosis often complex because of its many nonspecific symptoms (e.g. dyspnea, swollen ankles, lethargy) and signs (e.g. oedema) that are shared with other disease states such as respiratory disease, venous insufficiency, hypoalbuminemia, severe anemia, thyroid disease and hepatic and renal disease
- According to some estimates, an initial correct diagnosis is made in only 50% of patients
- Quick access to traditional diagnostic tools such as echocardiography to diagnose heart failure is often not possible or too expensive for some patients
- Hence there is need for a quick reliable test to rule out heart failure
What is BNP?
B-Type Natriuretic peptide (BNP) is a member of the natriuretic peptide family. It originates in the cardiac myocytes along with atrial natriuretic peptide (ANP) whereas C-Type natriuretic peptide originates in the endothelial cells. The function of these peptides is to regulate blood pressure, electrolyte balance and fluid volume.
The Relationship between BNP and Heart Failure
During heart failure, the stressed myocytes release increased levels of BNP into the circulatory system as a compensatory mechanism to increased intra-cardiac pressure and volume overload. BNP then binds to BNP receptors throughout the body to increase sodium excretion and diuresis, thereby reducing the concentration of hormones that cause hypertension and blood vessel constriction.
There are two options for testing cardiac natriuretic peptides:
- Assays that measure the active form, BNP or
- Assays that measure the inactive form, NT-proBNP
ProBNP, the precursor of BNP, when released into the circulation used under stress, is cleaved into two fragments: BNP and NT-proBNP. (Please refer to the below diagram)
The proBNP molecule cleaves to the inactive form, NT-proBNP, and
physiologically active BNP soon after release by the ventricles.
BNP & NT-proBNP physiological differences lead to differences in clearance rates and circulating half-lives:
- BNP with 3 mechanisms of clearance is cleared quickly with a half life of 20 mins
- NT-proBNP is cleared only by renal filtration and hence has a half life of 120 mins
This has two implications:
- BNP is believed to be a better real-time assessment of a patient's current condition
- Interpreting NT-proBNP results in patients with renal impairment is problematic
Clinical Applications of BNP
BNP promises to have a wide utility in the diagnosis and management of cardiac failure. While further work will extend its usage, the following are a summary of guidelines for its use from several published studies and a consensus panel on BNP published in 2004.1
- When used as an adjunctive tool to other clinical information, the BNP assay has a strong negative predictive value (99%) to rule out cardiac failure2
- To triage patients with acute dyspnea in conjunction with clinical information in an emergency setting:
- BNP < 100 pg/mL then heart failure highly unlikely
- BNP > 500 pg/mL then heart failure highly likely
- BNP is a significant independent predictor of mortality in HF. Changes in BNP over time are associated with morbidity and mortality. This provides physicians with an opportunity to provide more aggressive treatment to these patients
- Utilisation of BNP testing in conjunction with other clinical findings prior to echocardiography in at risk populations may reduce the overall cost of heart failure hospitalisation3
- High levels of natriuretic peptides identify those at greatest risk of future serious cardiovascular events including death
- Recent evidence suggest adjusting heart failure therapy in order to reduce natriuretic peptide levels may improve outcome4
BNP testing will be available at Gribbles Pathology from mid May 2006. The assay will be run daily at the main lab in PJ.
Specimen requirements = 4mL EDTA tube.
- Silver MA, Maisel A, Yancy C, et al., for the BNP Consensus Panel 2004. BNP Consensus Panel 2004: A Clinical Approach for the Diagnostic, Prognostic, Screening, Treatment Monitoring and Therapeutic Roles of Natriuretic Peptides in Cardiovascular Diseases. Congest Heart Fail 2004;5(supp 3):1-28
- Mair J et al. The impact of Cardiac Natriuretic Peptide Determination on the Diagnosis and Management of Heart Failure. Clin Chem Lab Med (2001;39(7):571-588)
- Muller C. et al. Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. New England Journal of Medicine 2004; 350: 647-54.
- W.J Remme, et al Guidelines for the diagnosis and treatment of chronic heart failure. European Heart Journal (2001)22, 1527-1560