NEWS & EVENTS

NEWS ARCHIVE | EDUCATIONAL RESOURCES

CARDIOVASCULAR NATRIURETIC PEPTIDES

A potential role of the heart, and specifically the atria, in the control of the vascular salt and water balance through the kidneys was theorized in the 1950s, specific atrial myocyte granules identified in the 1960s, and experiments in the late 1970s led to the discovery of atrial natriuretic peptide (ANP). Since that time, "B-type" (first discovered in brain tissue) natriuretic peptide (BNP), and "C-type" natriuretic peptide (CNP) have also been identified. Along with vasopressin, renin-angiotensin, and aldosterone, these newly identified peptide hormones comprise the fundamental physiologic hormonal mechanisms through which the human cardiovascular/renal salt/water/volume relationships are controlled. The natriuretic peptides work to counteract the effects of vasopressin, renin-angiotensin, and aldosterone and are cleared from the blood by a group of enzymes called neutral endopeptidases.

Natriuresis refers to the control of sodium excretion through the kidneys. ANP and BNP (after enzymatic activation of their prohormones) bring about excretion of sodium and water, and also are vasodilatory. CNP is misnamed in that its action appears to be primarily vasodilatory. ANP is released from the cardiac atria in response to increased central venous pressure, while BNP, residing in the both atrial and ventricular myocytes, is released in response to increased ventricular diastolic pressure and volume expansion.

Clinically, blood levels of these hormones and their precursors are elevated in congestive heart failure, myocardial infarction, volume and salt overload, cardiomyopathy, and mitral/aortic stenosis. It appears that BNP blood levels are more statistically predictive and clinically useful than are ANP levels. With the current testing methodology in use, the test specificity is greater than 98%, meaning that 2% or less of patients without CHF would test as (false) positive (high negative predictive value). BNP levels have been shown to be strongly predictive of survival in the clinical circumstance of heart failure after myocardial infarction. In patients with an acute coronary syndrome, a single early elevated blood level of BNP is associated with a higher risk of death, recurrent heart attack, development of heart failure or progression of heart failure. Further, BNP blood levels change very early in congestive heart failure and ventricular dysfunction, providing an inexpensive, non-invasive screen to determine if more invasive, expensive modalities are needed. BNP levels are also increased in renal failure, probably owing to volume overload, coexisting heart disease and/or decreased clearance of the peptides. BNP has been shown to have utility in distinguishing between the dyspnea of congestive heart failure and chronic obstructive pulmonary disease (COPD).

BNP blood levels are present in picogram per milliliter amounts. A cutoff of 80-100pg/mL has been demonstrated to provide an optimal combination of sensitivity and negative predictive value in the diagnosis of congestive heart failure. The basic research on the natriuretic hormones has been performed using radioimmunoassay or one of its variants. A chemiluminescent method suitable for routine laboratory analysis will soon be available. Currently, a point-of-care blood-testing device is in use.

Recently, a form of BNP produced by recombinant DNA technology has been approved by the FDA and is available for therapeutic use. This medication, called nesiritide (Natrecor, produced by the pharmaceutical company, Scios), is approved for use in the treatment of acutely decompensated heart failure. Nesiritide has been shown to decrease elevated pulmonary capillary wedge pressure, one of the key elements of CHF. Further, recall that BNP and related natriuretic peptides are removed from the blood by enzymes termed neutral endopeptidases. A new class of neutral endopeptidase inhibitors is under active development, the first of which (called omapatrilat) is expected to be released soon. These new enzyme inhibitors are expected to protect the natriuretic peptides present in the patients’ blood so they can better perform their functions.

This new rapidly expanding area of clinical laboratory testing, pharmaceutical and clinical research holds great promise to enable clinicians to more quickly and accurately identify and predict treatable cardiovascular abnormalities, attenuate their courses, preserve myocardium and cardiac functional capabilities, and use resources more effectively.

Physicians Reference Laboratory is pleased to announce the current availability of testing for brain-type natriuretic peptide (BNP). The specimen for testing is whole blood or plasma using EDTA as the anticoagulant. If testing cannot be accomplished within 4 hours, the separated plasma should be stored at -20 degrees C until tested.

Kenneth C. Cummings, MD
Chief, Clinical Pathology
May, 2002