NHLBI Scientists Find Blood Test Predicts Common
and Severe Complication of Sickle Cell Disease, and Identifies Patients
at Highest Risk of Death
Hormone Called BNP Detects Pulmonary Hypertension
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
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
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 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 black controls, since the disease
is more prevalent in blacks.
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 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 blacks and 1 in 1,000 -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
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
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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 www.nih.gov.