Hormone called BNP Detects Pulmonary Hypertension
NHLBI Scientists Find Blood Test Predicts Common and Severe Complication
of Sickle Cell Disease, and Identifies Patients at Highest Risk
of Death
A team of scientists with the National Heart, Lung, and Blood Institute
(NHLBI) of the National Institutes of Health has found that a hormone
detected in a simple blood test can identify patients with sickle
cell disease who have developed a life-threatening complication
called pulmonary hypertension. The team has also found that the
same hormone is a clear predictor of death in adult sickle cell
patients.
The hormone, called brain natriuretic peptide or BNP, is released
by the heart ventricles and helps predict death in heart failure
patients. The new study is published in the July 19 issue of the
Journal of the American Medical Association.
“This is an important leap forward in research on sickle
cell disease,” said NHLBI Director Elizabeth G. Nabel, M.D.
“Having a marker in the blood that will not only help identify
sickle cell patients with this deadly complication but also predict
those at the highest risk – will aid in the care and treatment
of these patients.”
Sickle cell anemia is one of the most common genetic blood disorders
in the United States. About 30 percent of sickle cell patients have
pulmonary hypertension. In this condition, there is constant high
blood pressure in the pulmonary arteries that supply the lungs.
This pressure leads to narrowed arteries, causing the heart to work
harder to pump blood. Pulmonary hypertension often leads to heart
failure and it is a major risk factor for death in adults with sickle
cell disease. Currently, echocardiograms and other heart tests are
used to diagnose pulmonary hypertension, but there has not been
a blood test to help detect the condition.
Previous research has found that in patients with pulmonary hypertension,
higher levels of BNP are associated with greater pressure in the
pulmonary arteries. NHLBI researchers theorized that BNP levels
might also correlate with the severity of pulmonary hypertension
and risk of death in sickle cell patients.
Lead scientist Roberto Machado, M.D., an investigator with NHLBI’s
Vascular Medicine Branch, and colleagues, including scientists in
the NIH Clinical Center, measured BNP levels in 230 patients with
sickle cell disease enrolled in the NIH Pulmonary Hypertension Screening
Study between 2001 and 2005. In order to confirm a diagnosis of
pulmonary hypertension, the patients were given echocardiograms
and other measurements of heart function. BNP levels were also measured
in 45 healthy African-American controls, since the disease is more
prevalent in African-Americans.
The scientists found that high blood levels of BNP – greater
than 160 pg/mL – in these patients independently predicted
mortality, increasing the risk of death by as high as fivefold.
The team also found that BNP levels could help identify the patients
with pulmonary hypertension. NIH study patients who had a BNP of
160 pg/mL or higher had a 78 percent chance of having pulmonary
hypertension identified by echocardiogram.
“We now have another tool to help diagnose pulmonary hypertension,”
Machado said. “There is tremendous value in diagnosing this
deadly complication early and accurately so we can aggressively
treat the complication and try to improve the patient’s outcome.”
To validate and confirm the findings, the team then measured BNP
levels in 121 stored blood samples from patients who had been enrolled
in a sickle cell drug treatment study, the Multicenter Study of
Hydroxyurea in Sickle Cell Anemia (MSH) Follow-up Study which began
in 1996. These patients came from major sickle cell centers around
the United States and at the time of enrollment it was not known
that pulmonary hypertension was a common complication of sickle
cell disease.
Thirty percent of patients in the MSH study had a BNP level greater
than 160 pg/ml, consistent with a diagnosis of pulmonary hypertension.
Most importantly, these patients had a threefold increased risk
of death compared with patients without pulmonary hypertension.
“The MSH analysis validated the connection between high BNP
blood levels, pulmonary hypertension and risk of death, found in
the NIH study patients,” said Mark Gladwin, M.D., chief of
NHLBI’s Vascular Medicine Branch. “It also revealed
that almost a third of sickle cell patients in the 1996 MSH study
had undiagnosed pulmonary hypertension. Perhaps the most intriguing
finding, these data suggest that it is pulmonary hypertension --
not painful crises or acute chest syndrome – that is the major
risk factor for death in adults with sickle cell disease.”
Acute chest syndrome is a life-threatening problem similar to pneumonia.
Sickle cell disease affects about 1 in 600 African-Americans and
1 in 1,000 to 1,400 Hispanic newborns every year. Patients with
this disease have abnormal hemoglobin molecules in their red blood
cells. The molecules damage the red cells, causing them to stick
to blood vessel walls and resulting in pain, organ damage, and anemia.
With the development of new treatments for the symptoms and complications
of sickle cell disease, patient survival has improved in recent
years.
Machado is optimistic regarding the future outlook for sickle cell
disease. “Based on these findings and other studies showing
that pulmonary hypertension is a major risk factor for death in
adult patients with sickle cell disease, there is great benefit
to screening sickle cell patients with both echocardiography and
blood BNP. By combining these tests, we hope to identify patients
who can be treated more intensely to improve the management of their
disease and hopefully their survival,” he said.
Machado added that identifying these patients will bring them to
the attention of scientists engaged in clinical trials of new treatments
for the disease. He noted that NHLBI is currently participating
in a multi-center study to test the safety and effectiveness of
the drug bosentan in patients with sickle cell disease and pulmonary
hypertension. An NHLBI-sponsored clinical trial studying the effects
of sildenafil as a treatment for pulmonary hypertension in sickle
cell disease is expected to begin recruiting patients early in 2007.
To interview an NHLBI spokesperson, contact the NHLBI Communications
Office at 301-496-4236.
For
information on sickle cell disease (http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_WhatIs.html).
For
information on pulmonary hypertension (http://www.nhlbi.nih.gov/health/dci/Diseases/pah/pah_what.html).
Part of the National Institutes of Health, the National Heart,
Lung, and Blood Institute (NHLBI) plans, conducts, and supports
research related to the causes, prevention, diagnosis, and treatment
of heart, blood vessel, lung, and blood diseases; and sleep disorders.
The Institute also administers national health education campaigns
on women and heart disease, healthy weight for children, and other
topics. NHLBI press releases and other materials are available online
at: www.nhlbi.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and Centers
and is a component of the U. S. Department of Health and Human Services.
It is the primary federal agency for conducting and supporting basic,
clinical, and translational medical research, and it investigates
the causes, treatments, and cures for both common and rare diseases.
For more information about NIH and its programs, visit http://www.nih.gov.
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