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Blood Test Predicts Sickle Cell Disease Complication, Identifies Patients At High Risk Of Death

Date:
July 19, 2006
Source:
NIH/National Heart, Lung, and Blood Institute
Summary:
A team of scientists with the National Heart, Lung, and Blood Institute 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 is called brain natriuretic peptide or BNP.

The sickle-shaped red blood cells tend to get stuck in blood vessels, blocking the flow of blood.
Credit: Image courtesy of NIH/National Heart, Lung, and Blood Institute

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.

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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 β€" 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 β€" greater than 160 pg/mL β€" 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 patientβ€TMs 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 NHLBIβ€TMs 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 β€" 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.


Story Source:

The above story is based on materials provided by NIH/National Heart, Lung, and Blood Institute. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Heart, Lung, and Blood Institute. "Blood Test Predicts Sickle Cell Disease Complication, Identifies Patients At High Risk Of Death." ScienceDaily. ScienceDaily, 19 July 2006. <www.sciencedaily.com/releases/2006/07/060718175959.htm>.
NIH/National Heart, Lung, and Blood Institute. (2006, July 19). Blood Test Predicts Sickle Cell Disease Complication, Identifies Patients At High Risk Of Death. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2006/07/060718175959.htm
NIH/National Heart, Lung, and Blood Institute. "Blood Test Predicts Sickle Cell Disease Complication, Identifies Patients At High Risk Of Death." ScienceDaily. www.sciencedaily.com/releases/2006/07/060718175959.htm (accessed December 22, 2014).

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