Natriuretic Peptides
Description
A variety of neurohormones, including the group of natriuretic peptides (ANP, BNP), help maintain fluid homeostasis in the healthy individual. These hormones oppose the actions of the renin-angiotensin-aldosterone system in response to short-term perturbations in fluid balance.Atrial natriuretic peptide (ANP):
- 28-amino-acid peptide hormone released from the atria into the circulation
- Main stimulus for release of ANP is atrial stretch
- Dilation of the afferent glomerular arteriole and constriction of the efferent arteriole, resulting in increased filtration pressure. Sodium reabsorption is inhibited in the collecting duct; both mechanisms cause increased natriuresis.
- Opposes angiotensin effects on aldosterone and renin release, vascular tone, vascular mitogenesis, and renal sodium absorption, further promoting natriuresis; increases vascular permeability
- Antimitotic effect in vitro
- Central nervous system effects: Decreased salt appetite, decreased thirst, decreasedcorticotropin release
- All of the effects noted previously result in lowered plasma volume and lowered blood pressure.
Brain natriuretic peptide (BNP) and N-terminal pro Brain natriuretic peptide (NT-pro BNP)
- Discovered in brain homogenate
- Secreted in the ventricles, less in the atria
- Cleaved into biologically active (BNP) and inactive (NT-proBNP) forms
- BNP has similar natriuretic and central effects to those of ANP
- Kidney: Natriuresis nearly as strong as ANP
- Release of BNP is increased in response to high ventricular filling pressures
- BNP circulating concentration is usually <20% of ANP, but can exceed levels of ANP in heart failure, making BNP and NT-pro BNP useful peptides to measure in acute heart failure.
Assay:Initially, immunoradiometric assays were used to measure levels of BNP but were replaced by a “rapid” assay using a fluorescence immunoassay
Results within 10–15 minutes
The “normal range” of BNP and NT-proBNP levels depends upon the clinical disorder in question and the prevalence of that disease in the population. In young adults, most will have BNP <25 pg/mL and NT-proBNP <70 pg/mL. However, natriuretic peptide levels are known to increase with age, and age-normalized values, particularly for NT-proBNP, have been recommended.
Marker of LV dysfunction
Natriuretic peptides in patients with acute dyspnea:In patients presenting to the emergency department, BNP levels >100 pg/mL diagnosed heart failure with a sensitivity of 90% and a specificity of 76%.
The overall predictive accuracy was 83%, which is as good or superior to a history consistent with heart failure, findings of rales on exam, and cardiomegaly on CXR. BNP is also superior to both the Framingham and National Health and Nutrition Examination Survey (NHANES) criteria for heart failure.
In a 2nd study of patients presenting to the emergency department with acute dyspnea, a NT-pro BNP level <300 pg/mL was used to effectively exclude decompensated HF, with a 98% negative predictive value.
To confirm the diagnosis of heart failure in the acutely dyspneic patient, an NT-proBNP >1,000 pg/mL has been suggested as an age-independent value with an acceptable positive predictive value.
Patients with permanent/paroxysmal atrial fibrillation have significantly higher circulating levels of BNP and therefore a cutoff of at least 200 pg/mL should be used.
Although BNP and NT-pro BNP have been shown to have a high sensitivity for detecting
heart failure, they should not be used alone for diagnosis, and are best used in conjunction with other data and clinical judgment to confirm or exclude a diagnosis of heart failure.
Natriuretic peptides and prognosis:Elevated natriuretic peptide levels in heart failure are predictors of increased morbidity and mortality. Changes in BNP and NT-pro BNP over time correlate with changes in morbidity and mortality in patients with heart failure.
Data regarding the use of natriuretic peptides to guide medical therapy are sparse. However, the failure to observe a decline in natriuretic peptides during an inpatient stay for HF is an ominous sign. Some authors have recommended checking BNP and NT-pro BNP levels at the time of admission for acutely decompensated HF, and at the time of discharge, when the patient is thought to be at his “dry weight.”
Elevated natriuretic peptide levels have been shown to predict short-term (30-day) and long-term (10-mo) morbidity and mortality in patients presenting with acute coronary syndromes.
BNP as a screening tool for LV dysfunction:Use of BNP and NT-pro BNP as indicators of preclinical ventricular dysfunction has not yet been proven to be efficacious.
Potential sources of error:BNP and NT-proBNP levels increase with age and are increased in females.
BNP and NT-proBNP levels are increased in patients with glomerular filtration rate (GFR) <60, regardless of whether they clinically have heart failure. Therefore, monitoring BNP in this subset of patients may not facilitate management of heart failure.
Other causes of elevated natriuretic peptides include: Pulmonary embolism, high output states, sepsis, atrial fibrillation, and valvular heart disease.
Obese patients have BNP and NT-pro BNP levels that are lower than expected.
Results within 10–15 minutes
The “normal range” of BNP and NT-proBNP levels depends upon the clinical disorder in question and the prevalence of that disease in the population. In young adults, most will have BNP <25 pg/mL and NT-proBNP <70 pg/mL. However, natriuretic peptide levels are known to increase with age, and age-normalized values, particularly for NT-proBNP, have been recommended.
Marker of LV dysfunction
Natriuretic peptides in patients with acute dyspnea:In patients presenting to the emergency department, BNP levels >100 pg/mL diagnosed heart failure with a sensitivity of 90% and a specificity of 76%.
The overall predictive accuracy was 83%, which is as good or superior to a history consistent with heart failure, findings of rales on exam, and cardiomegaly on CXR. BNP is also superior to both the Framingham and National Health and Nutrition Examination Survey (NHANES) criteria for heart failure.
In a 2nd study of patients presenting to the emergency department with acute dyspnea, a NT-pro BNP level <300 pg/mL was used to effectively exclude decompensated HF, with a 98% negative predictive value.
To confirm the diagnosis of heart failure in the acutely dyspneic patient, an NT-proBNP >1,000 pg/mL has been suggested as an age-independent value with an acceptable positive predictive value.
Patients with permanent/paroxysmal atrial fibrillation have significantly higher circulating levels of BNP and therefore a cutoff of at least 200 pg/mL should be used.
Although BNP and NT-pro BNP have been shown to have a high sensitivity for detecting
heart failure, they should not be used alone for diagnosis, and are best used in conjunction with other data and clinical judgment to confirm or exclude a diagnosis of heart failure.
Natriuretic peptides and prognosis:Elevated natriuretic peptide levels in heart failure are predictors of increased morbidity and mortality. Changes in BNP and NT-pro BNP over time correlate with changes in morbidity and mortality in patients with heart failure.
Data regarding the use of natriuretic peptides to guide medical therapy are sparse. However, the failure to observe a decline in natriuretic peptides during an inpatient stay for HF is an ominous sign. Some authors have recommended checking BNP and NT-pro BNP levels at the time of admission for acutely decompensated HF, and at the time of discharge, when the patient is thought to be at his “dry weight.”
Elevated natriuretic peptide levels have been shown to predict short-term (30-day) and long-term (10-mo) morbidity and mortality in patients presenting with acute coronary syndromes.
BNP as a screening tool for LV dysfunction:Use of BNP and NT-pro BNP as indicators of preclinical ventricular dysfunction has not yet been proven to be efficacious.
Potential sources of error:BNP and NT-proBNP levels increase with age and are increased in females.
BNP and NT-proBNP levels are increased in patients with glomerular filtration rate (GFR) <60, regardless of whether they clinically have heart failure. Therefore, monitoring BNP in this subset of patients may not facilitate management of heart failure.
Other causes of elevated natriuretic peptides include: Pulmonary embolism, high output states, sepsis, atrial fibrillation, and valvular heart disease.
Obese patients have BNP and NT-pro BNP levels that are lower than expected.
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