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B-Type Natriuretic Peptide

The natriuretic peptide system is comprised of 3 peptide hormones including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP).  ANP is synthesized mainly by cardiac myocytes in the atria. Very little ANP is produced by ventricular tissue.  Increased atrial wall tension, reflecting increased intravascular volume, is the dominant stimulus for its release. BNP, also known as brain natriuretic hormone, because it was first isolated from porcine brain, is synthesized primarily by ventricular myocytes.  It is continuously released in response to both ventricle volume expansion and pressure overload.  CNP is produced by brain, pituitary, kidney and endothelial cells.  Its plasma concentration is very low, and its major action is vasodilatory rather than natriuretic.  

The natriuretic peptides are natural antagonists to the renin-angiotensin-aldosterone (RAA) system in regulating arterial pressure. The kidneys release renin in response to a decrease in arterial pressure. Renin triggers an enzymatic cascade that results in the production of angiotensin II, which causes vasoconstriction, retention of salt and water by the kidneys and secretion of aldosterone by the adrenals.  Aldosterone stimulates the renal tubules to reabsorb sodium.  As blood pressure and intra-cardiac pressure rise, atria and ventricles secrete ANP and BNP. These molecules promote sodium and water excretion by increasing GFR and inhibiting sodium reabsorption by the kidney. Thus, they counteract the RAA system by reducing blood pressure and extracellular volume.

Plasma levels of ANP and BNP are increased in disorders associated with intravascular volume overload, increased central venous pressure and left ventricular dysfunction.  Because of this association, there has been much interest in using ANP and BNP as biomarkers for heart failure. Recent studies have demonstrated that BNP is a 

better index of heart failure than ANP.  BNP measurements may be useful in the following clinical situations.

  • Differentiating CHF from pulmonary disease 
  • Screening for CHF in high-risk patients
  • Determining CHF severity
  • Monitoring CHF therapy
  • Risk stratification after acute MI
  • Assessing left ventricular hypertrophy in dialysis patients
  • Assessing chemotherapy cardiotoxicity

Blood BNP levels increase two to three-fold with age, especially after age 75.  Females have higher values than males.  

Mean BNP Concentration by Age




45 – 54



55 – 64



65 – 74







A BNP cutoff point of 100 pg/mL allows for the increased levels seen with advancing age and provides good discrimination between CHF and non-CHF causes of dyspnea.  Very high or very low BNP levels are helpful diagnostically for these patients. A dyspneic person with a BNP <100 has less than a 5% likelihood of having CHF. The grey zone of accepted cutoffs for BNP is 100-500 pg/mL. Therefore, the rule-in cutoff for BNP is >500 pg/mL for patients of all ages. 

A person with known heart disease, who has a BNP level >1200 most likely does have CHF. Unfortunately, cardiac diseases other than CHF can produce BNP levels between 100 and 1200. This is the reason why the specificity of BNP for CHF is only 70 to 75%. 

Acute pulmonary embolism may produce BNP levels around 200 pg/mL. BNP may not be elevated in very acute CHF or with ventricular inflow obstruction such as occurs in hypertrophic obstructive cardiomyopathy, mitral stenosis and atrial myxoma.  

BNP is an objective indicator of CHF severity.  BNP mean concentrations progressively increase from New York Heart Association (NYHA) class I to IV.  However, the range of BNP concentrations within one NYHA class substantially overlaps with the next higher class.  

BNP Values in CHF

NYHA Class

Mean BNP










Since its introduction, many physicians have begun ordering daily BNP levels to monitor therapy. However, the value of this BNP application has never been proven.  A recent article investigating the biological variability of BNP within an individual patient strongly suggests that serial monitoring is not good practice (Clinical Chemistry 2004; 50: 2052-58). The within day, day-to-day and week-to-week variability of BNP in 43 patients with stable chronic heart failure and a left ventricular ejection fraction <40% was studied. BNP levels ranged from 100 to 1630, with a median of 134. Within day variation was calculated from six samples that were collected every 2 hours starting at 08:00. Day to day variation was calculated from five samples collected between 08:00 and 10:00 on consecutive days within 1 week. Week to week variation was calculated on samples drawn between 08:00 and 10:00 once weekly for 6 consecutive weeks. The analytical imprecision of BNP measurement was 8.4%.

BNP values within individual patients fluctuated as much as 12% during a single day, 27% from day to day, and 41% from week to week. BNP increased 25% during the day, with the lowest values occurring in the morning and the highest values in the evening. Using biological variation and analytical imprecision, it is possible to calculate how much BNP must change to be medically significant.  

BNP Variability

Medically Significant Change

Within Day


Day to Day


Week to Week



As seen in the table, BNP must change almost twofold from one day to the next, or one week to the next to be medically significant. This magnitude of change is greater than the 45 - 55% reduction in BNP that is expected with standard CHF therapy. Also, the majority of patients required more than 5 days of treatment to decrease their BNP levels more than the fluctuation due to biological variation. This study clearly demonstrates that daily orders for BNP are not warranted or helpful. In most cases, BNP should only be ordered twice during an admission: once for diagnosis and then again prior to discharge.  

Also, it is important to remember that specimens for BNP levels should be drawn at the same time of the day to eliminate diurnal variation. BNP should not be measured while a patient is receiving nesiritide (Natrecor) because results will be falsely elevated. The BNP assay measures the same peptide that is present in nesiritide Maximum decrease in endogenous BNP will be detected at 6 hours post-infusion.  

Because MI is a major cause of CHF, BNP has been evaluated as a cardiac risk factor in patients presenting with an acute coronary syndrome.  A single BNP measurement taken approximately 2 days after the onset of ischemic symptoms has prognostic value in patients with acute MI with ST-segment elevation, acute MI without ST-segment elevation and unstable angina.  Patients with a BNP level >81 pg/mL are significantly more likely to die, have a recurrent MI, or have progressive heart failure.  

BNP is elevated in patients with end stage renal disease undergoing dialysis.  However, the increase is attributed to left ventricular hypertrophy and not renal dysfunction. An elevated level is associated with higher cardiac mortality.  

Specimen requirement is one lavender top tube of blood. BNP is not very stable, and testing should optimally occur within 4 hours after collection. Serum level decreases approximately 10% during refrigerated storage for 8 hours. Testing is available 24 hours a day and can be performed on a stat basis.  


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