B-type natriuretic peptide (BNP) is a hormone that is secreted from cardiac ventricular myocytes in response to myocardial stretch and stress. Its release activates a cascade of pathways resulting in an overall protective effect on the myocardium, particularly those of natriuresis and vasodilation. Serum BNP levels are increased in patients with congestive heart failure (CHF) and are clinically useful in the diagnosis and exclusion of CHF exacerbation. Increased levels may also predict prognosis and adverse outcomes of patients with cardiac disease.
BNP was initially identified in porcine brain tissue in 1988 and was previously referred to as “brain natriuretic peptide.” Later, researchers determined that the primary site of its release are cardiac ventricular cells, particularly in the setting of ventricular distention. Following this discovery, an abundance of literature emerged regarding the utilization of BNP as a potential biomarker to measure the presence and severity of HF.
When exposed to stretch, cardiac ventricular cells secrete BNP, which they release as the prohormone, proBNP. The prohormone is then enzymatically cleaved to form the 76-amino acid peptide, NT-proBNP, and the 32-amino acid peptide, BNP. Both BNP and NT-proBNP are commonly measured in a clinical setting.
Following systemic secretion, the natriuretic peptides activate transmembrane guanylate cyclases on the surface endothelial cells, thereby increasing intracellular levels of cyclic guanosine monophosphate (cGMP), leading to vasodilation. Other systemic effects include diuresis and natriuresis, resulting in lowered blood pressures. The peptides have also demonstrated the ability to antagonize adverse pathways that are over-activated in the setting of heart failure, for example, the renin-angiotensin-aldosterone axis (RAAS), which has anti-diuretic effects, and the transforming growth factor-beta pathway, which increases cardiac remodeling and fibrosis.
In healthy individuals, b-type natriuretic peptide levels vary by age and gender; levels increase with increasing age and are higher on average in women than in men. A normal BNP level in a healthy individual is less than 100 pg/ml.
Because of its longer half-life, serum NT-proBNP levels are approximately six times higher than that of BNP. Like BNP, its concentrations vary by age; the threshold of normal for those less than 50 years of age is 450 pg/ml, while it is 900 pg/ml for those greater than 50 years of age. The clinical importance of measuring one peptide over the other has not yet been demonstrated.
Both BNP and NT-proBNP levels testing through standard blood draws. There are also point-of-care BNP assays, which take approximately fifteen minutes for results and are often useful in emergent settings.
BNP and NT-proBNP levels may be affected by the presence of specific comorbidities, such as chronic renal failure, type 2 diabetes, obesity, and acute coronary syndrome. Levels are higher in patients with renal failure, diabetes, and acute coronary syndrome (ACS), and lower in obese individuals. Therefore, comparisons of levels among patients are less meaningful than tracking an individual patient's peptide trajectory.
BNP and NT-proBNP levels elevate in patients with cardiac disease due to myocardial stress and volume overload. Patients with a BNP elevation of over 100 pg/ml should be assessed further for the signs and symptoms of cardiac disease. Though BNP is traditionally used in the diagnosis of left ventricular systolic function, it can be elevated through other processes as well, for example, in the setting of right ventricular failure, acute myocardial infarction, congenital heart disease, and valvular disease.
Congestive Heart Failure
The strongest indication for BNP measurement is in distinguishing between cardiogenic and non-cardiogenic causes of dyspnea in an emergent setting. Dyspnea is a symptom in nearly all cases of CHF exacerbation. However, it is not specific to CHF and may be the result of other pathologic processes. The sensitivity of BNP in heart failure is approximately 97%. Therefore a normal BNP level (less than 100 pg/ml) virtually excludes heart failure and should prompt a search for noncardiac causes of dyspnea. An elevated level may indicate the presence of cardiac disease and the need for further cardiac workup, for example, with echocardiography, to determine the etiology of the patient's symptoms. Furthermore, short-term elevations in hospitalized patients with CHF have correlated with longer hospital stays.
BNP can also be a useful prognostic marker in patients with known chronic heart failure; elevated levels are found in patients with higher New York Heart Association functional class scores and correlate with mortality and morbidity as well as recurrent hospital admission. Furthermore, in hospitalized patients with heart failure, short-term elevations in BNP have been shown to predict increased hospital stays.
Acute Coronary Syndrome
Left ventricular dysfunction due to cardiac remodeling is a significant cause of mortality following myocardial infarction. BNP monitoring can help to assess prognosis following MI because it becomes elevated in patients with post-MI LV dysfunction with ejection fractions <40%.
While BNP is a useful tool in assessing prognosis in patients with cardiac disease, it has not been well established that BNP-guided therapy offers improved outcomes when compared to symptom-guided therapies. Therefore, knowledge of BNP levels may predict outcomes but does not yet dictate treatment in the chronic management of heart failure. For this reason, BNP should not be used as a stand-alone test when guiding therapy in cardiac disease. Furthermore, while elevated BNP levels are highly sensitive to heart failure, they are not specific to its cause; elevated BNPs may be seen in a variety of cardiac and noncardiac diseases, as previously mentioned. It is, therefore, necessary to follow abnormal BNP levels with further cardiac testing. Particular care is necessary in the evaluation of an elevated BNP in patients with multiple comorbidities, for example, those with renal failure, to identify the cause of the peptide's increase.
Heart failure is a significant and growing cause of morbidity and mortality in the US; it is the leading cause of hospitalization in those aged 65 and older and is responsible for 10% of all health care expenditures. Many of the symptoms of heart failure exacerbations are not specific to the disease process; therefore, identifying a biomarker that could assist in the diagnosis process was critical. BNP measurement is a highly sensitive, low-cost, and rapid test that can be utilized in hospitals to assist in the diagnosis of heart failure.
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