It's not common for a new diagnostic test to have an immediate impact on clinical practice, but BNP (B-type natriuretic peptide) is just such a test. Best of all, it's a simple, safe blood test that can help doctors evaluate complex cardiac functions.
What is BNP?
BNP belongs to a family of protein hormones called natriuretic peptides. Each member of the group is produced by a different part of the circulatory system. ANP is produced by the muscle cells in the upper pumping chambers of the heart (the atria); BNP is produced in the larger and more powerful lower chambers (the ventricles); CNP is produced mainly in blood vessels; and DNP is found in the blood plasma but probably originates in the heart itself.
These natriuretic peptides have an important role in regulating the circulation. Scientists have learned the most about ANP and BNP. Both act on blood vessels, causing them to dilate, or widen. They also work on the kidneys, causing them to excrete more salt and water. In addition, the natriuretic peptides reduce the production of various hormones that narrow blood vessels, boost the heart rate, or affect fluid retention; examples include adrenaline, angiotensin, and aldosterone.
The net effect of natriuretic peptides is to promote urine excretion, relax blood vessels, lower blood pressure, and reduce the heart's workload. They are part of the body's natural defense mechanisms designed to protect the heart from stress. And they surge into action when they are needed most, when the heart itself is under siege.
BNP in CHF
It sounds like alphabet soup, but it's actually modern cardiology at its best. BNP helps the body compensate for congestive heart failure (CHF); measurements of BNP help doctors diagnose and treat this serious condition.
CHF results when the heart muscle is weakened. The most common causes are coronary artery disease and hypertension. In other cases, heart valve disease is to blame. Less often, various heart muscle diseases (cardiomyopathies) are responsible; in men, their chief causes include viral infections, alcohol abuse, excessively high iron levels, and certain genetic disorders.
The heart's job is to collect blood from the veins, then pump it through the arteries to all the body's tissues. In CHF, the weakened pump is not up to the task; the tissues don't get all the oxygen-rich blood they need, and blood backs up in the lungs and then the veins.
The lack of sufficient tissue oxygen makes people with CHF feel weak and tired. Muscle function suffers, making it hard to get around. Kidney function is also impaired, sometimes permanently, adding to the fatigue and complicating treatment. Deprived of its full complement of blood, the brain can slow down along with the rest of the body, producing lethargy, confusion, and even grogginess.
The backup of blood produces even more symptoms; it's what puts the congestion in congestive heart failure. Shortness of breath is a prime complaint. At first, it occurs only during physical exertion, but advanced CHF makes breathing a chore even at rest. Patients with CHF often need to sleep on extra pillows because they get terribly winded if they lie flat; they can even be awakened by shortness of breath so severe that they have to sit bolt upright. Wheezing and coughing are also among the congestive symptoms of CHF, and the wet lungs are unusually susceptible to pneumonia. Worst of all is acute pulmonary edema, a critical shortness of breath due to fluid in the lungs that requires immediate treatment.
As fluid builds up, it can accumulate elsewhere in the body. Because gravity draws fluid downward, the feet and legs often become puffy during the day, only to slim down in bed at night. In addition, the abdomen may become bloated, and fluid in the liver can cause damage that may be permanent (cardiac cirrhosis). Fluid can also accumulate in the scrotum and penis, producing swelling that can be substantial.
Urinary symptoms are common in CHF, and they may confuse older men who also have symptoms of benign prostatic hyperplasia (BPH). Patients with mild to moderate CHF have to urinate frequently at night, just like men with BPH. In severe CHF, though, urine output is diminished both day and night.
Advanced CHF can also produce severe weakness, loss of appetite, and weight loss known as cardiac cachexia. These patients look as if they have widespread cancer, not heart disease. In fact, they are just as sick.
About five million Americans have CHF, and more than a half-million more join the ranks each year. It's a very serious condition, but treatments have produced major advances. But to treat CHF, you first have to diagnose it "" and that's where BNP fits in.
Doctors can usually diagnose advanced CHF on clinical grounds, confirmed by simple studies like chest x-rays, EKGs, and routine blood tests. But milder CHF can be tricky to recognize, and various lung diseases, liver diseases, and kidney diseases can mimic CHF. So when doctors suspect CHF, they usually order an echocardiogram to confirm the diagnosis and assess its severity. Echocardiograms are safe, but they are relatively expensive and may be hard to come by in some communities. While the BNP test will never replace echocardiography, it has already helped doctors reserve the test for patients who really need it.
In CHF, the heart chambers are dilated, or enlarged. Heart muscle cells are stretched as the chambers swell with extra blood that can't be pumped out efficiently. The stretched muscle cells produce extra BNP, which pours into the bloodstream. And doctors now have simple, accurate, inexpensive tests to measure BNP in blood samples. A bedside test can even yield diagnostic information right in the Emergency Department.
BNP is very helpful in diagnosing CHF. A normal BNP level is about 98% accurate in ruling out the diagnosis, freeing doctors to hunt for other conditions that may be causing shortness of breath or fluid retention. In most labs, levels below 100 picograms per milliliter (pg/ml) rule out CHF (the cutoff is 200 pg/ml for patients with kidney failure). High BNP levels are less conclusive, but in patients with suspected CHF, levels of about 900 pg/ml in 50- to 75-year-olds or above 1,200 pg/ml in older patients support the diagnosis up to 90% of the time; most of the patients who do not have true CHF have elevated BNPs due to severe lung or kidney disease. The table below lists some of the conditions that can raise or lower BNP levels.
Noncardiac conditions that change BNP levels
High blood pressure
Excessive cortisol levels
Advanced liver disease
Certain rare tumors
Ace inhibitorsSpironolactoneDiureticsBeta blockers
BNP is very helpful in determining the outlook for patients with CHF. In general, the higher the level, the worse it is. Finally, BNP is very helpful in guiding the treatment of CHF. Effective therapy reduces the backup of blood in the heart. The heart chambers get smaller, and as the muscle cells recover from being stretched, they produce less BNP. When doctors see falling BNP levels, they breathe a sigh of relief; more important, their patients breathe better.
BNP in CAD
The cardiologists are at it again, this time exploring the role of BNP in coronary artery disease (CAD). Patients who have CAD without CHF don't have stretched heart muscle cells, but if their coronary artery blockages are extensive or if the vascular inflammation in the plaques is active, the muscle cells will be ischemic "" that is, they won't be getting enough oxygen to keep them happy. Like stretched muscle cells, ischemic cells make and release extra BNP "" not enough to register in the CHF range, but enough to push the levels up, typically between 20 and 100 pg/ml.
Measuring BNP to help diagnose and treat CHF is well established, but using it for CAD is still experimental. Nevertheless, scientists have reported that BNP levels bump up during treadmill stress tests in patients with CAD; in one study, BNP levels rose from 15 pg/ml at rest to 35 pg/ml immediately after exercise, only to drift down to 20 pg/ml within 15 minutes. In another study of patients with suspected angina, BNP levels averaged 12 pg/ml in patients who turned out to have healthy coronary arteries, but they averaged 16 pg/ml, 19 pg/ml, and 39 pg/ml respectively in patients who had blockages in one, two, or three of their coronary arteries. And in patients who had BNP levels measured when they were hospitalized for acute coronary events, high BNP levels predicted a high risk of death during the next two years.
BNP testing will never replace treadmill tests, heart scans, or coronary angiography for patients with suspected or proven CAD. But research suggests that this simple test may soon help doctors tell which patients need fancy tests and which don't. And the test has already improved the diagnosis and treatment of CHF. That's a big gain for a small protein.