Biochemical markers for cardiac failure
Natriuretic peptides were discovered when the infusion of atrial extracts into rats caused a
copious natriuresis and diuresis.
Subsequent research led to the discovery of a family of natriuretic peptides, consisting
mainly of 3 peptides, which differ in their tissue distribution and receptor type.
• Atrial Natriuretic Peptide (ANP) • Mainly in the atria
• Brain Natriuretic Peptide (BNP) • Mainly in the atria
• C-type Natriuretic Peptide (CNP) • Central Nervous System, Kidney, Vascular Endothelium
NT-pro Brain Natriuretic Peptide (NT-proBNP) is the N-terminal part of BNP.
P H Y S I O LO G Y
The main stimulus for ANP and BNP secretion is increased atrial wall tension, reflecting
increased intravascular volume. The main physiological effect of ANP and BNP is one of
natriuresis and diuresis. Furthermore, ANP also reduces peripheral vascular tonus.
The net effect is the lowering of blood pressure in order to protect the heart from volume
P A T H O P H Y S I O LO G Y
The main purpose of natriuretic peptides is to protect the body against salt and water
Excessive atrial wall tension (volume overload) further increases plasma ANP and BNP
Congestive heart failure stimulates cardiac myocyte ANP and BNP synthesis leading to
increased plasma levels.
Cardiac hypertrophy further increases ANP and BNP secretion from the cardiac ventricles.
Under normal conditions only minute amounts of ANP originate from the ventricles. The
plasma levels are directly proportional to the degree of heart failure.
WHICH MARKER FOR CARDIAC FAILURE?
BNP/NT-proBNP are currently described as the best markers for cardiac failure. Apart from
BNP levels increasing with cardiac failure and ventricular hypertrophy, BNP synthesis and
secretion is more rapid than that of ANP from ventricular myocytes in cardiac failure.
BNP/NT-proBNP are superior regarding stability in serum and analytical methods available
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BN P I N P RA C T I C E
Echocardiography is the gold standard for diagnosis of cardiac failure. Unfortunately
echocardiography is not readily available in primary health care and general practice
BNP can detect symptomatic and asymptomatic heart failure with a high degree of
sensitivity. With asymptomatic heart failure the specificity of BNP is low, as BNP increases
with any form of cardiac pathology.
Normal plasma BNP concentration excludes cardiac failure in 99% of cases (negative
predictive value is 99%). An increased BNP plasma level is indicative of cardiac failure, but
other causes of an increased BNP plasma level need to be excluded. Further investigation,
e.g. echocardiography, needs to be considered if clinically indicated.
Please note: Only mild to moderate increases of BNP levels are seen with non-cardiac
CAUSES OF INCREASED BNP CONCENTRATION
• • Heart failure (any cause of heart failure)
• • Myocardial infarction
• • Left ventricular hypertrophy
• • Cardiomyopathy
• • Chronic renal failure
• • Chronic obstructive lung disease
• • Beta-blockers
• • Atrial fibrillation
CAUSES OF A DECREASED BNP
• • Furosemide diuretics
• • Hypothyroidism
• • Vasodilators
• • ACE-inhibitors
It is important to consider the influence of beta-blockers, furosemide diuretics, vasodilators
and ACE-inhibitors when interpreting BNP plasma concentrations.
BNP/NT-proBNP are useful biochemical markers to exclude cardiac failure in clinical
BNP is currently being researched for the following clinical uses:
• Predicting of prognosis in congestive cardiac failure
• Identification of high-risk patients post-myocardial infarction
• Monitoring of cardiac failure therapy
RE F E R E N C E S
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myocardial Infarction. Clinical Cardiology: Vol 23, pp. 921-927; 2000
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