These findings from scientists at St. Jude Children's Research Hospital are published in the July issue of Radiology. This novel finding may help explain why African-American men between 33 and 44 years of age are three to four times more likely to suffer a stroke than American white men of the same age, according to Grant Steen, Ph.D., an associate member in the Department of Radiological Sciences at St. Jude and associate professor in the Departments of Pediatrics and Radiology at the University of Tennessee School of Medicine.
"We've shown that apparently healthy siblings of children with SCD can develop a blood vessel abnormality in childhood that could become a serious health threat during adulthood," Steen said.
Many factors contribute to the increased risk for stroke among African-American adults. About a third of the overall increased risk is associated with greater exposure to the known risk factors: high blood pressure, high cholesterol, smoking, obesity and diabetes. Another third of the increased risk is probably due to factors that relate to poverty, such as stress, according to Steen. Until now there was no evidence to help explain the remaining third of the increased risk for stroke in African-Americans.
SCD is caused by abnormal hemoglobin--the oxygen-carrying protein inside red blood cells. These abnormal hemoglobin molecules bind together in long chains after releasing their oxygen to the body. These chains force the red blood cells to flatten and bend into the sickle shape characteristic of the disease. When the red cells pick up more oxygen in the lungs, the hemoglobin molecules separate, and the cells spring back to their normal shape. But the repeated sickling and unsickling of red cells that contain this abnormal hemoglobin shortens the lives of these red cells. The cells die faster than the body can replace them, and the heart tries to compensate for this loss of healthy red cells by significantly increasing the flow of blood, according to Steen.
"Instead of a garden hose bringing blood to the brain, you have a fire hose," Steen said.
Steen believes that the high rate of blood flow damages arteries in the brain, causing them to become twisted or "tortuous." As these children grow older, the tortuous arteries may fail to supply the brain with sufficient blood, thus setting the stage for a stroke in adulthood.
"In fact, when we look at the blood vessels in the brains of these children, they tend to look like those of a 65-year-old adult with high blood pressure," Steen said. "Yet they don't show any symptoms during childhood. This appears to be a hidden public health problem." Children who have inherited only one sickle cell disease gene from a parent do not show signs of the disease, and are referred to as having hemoglobin AS (A = normal). Children who have not inherited any sickle genes are referred to as having hemoglobin AA. The amount of abnormal hemoglobin S in children with hemoglobin AS can vary from 20 percent to 40 percent. The St. Jude study suggests that, in siblings with high hemoglobin S, the abnormal hemoglobin can cause a high rate of blood flow, which may occur to compensate for the loss of red cells. Steen believes that it may be the high rate of blood flow that damages arteries, since children with more hemoglobin S also had more tortuousity.
Steen and his colleagues believe that as children with hemoglobin AS grow into adults, the tortuousity of blood vessels in their brains may increase. In fact, based on the number of people with AS in the U.S. (2.7 million) and the amount of tortuousity found in siblings with AS in this study, the St. Jude researchers estimate that there may be more than 135,000 people in the U.S. with AS-related blood vessel tortuousity.
"If these findings are confirmed, it would suggest that children with sickle trait (hemoglobin AS) should be tested to see if they have a high percentage of hemoglobin S," Steen said.
The scientists hope to continue this investigation with a much larger study, which would track children and young adults in different age groups over time to see if there is a progression toward arterial tortuousity and stroke.
Other authors of this paper include Gisele Hankins, R.N. and Xiaoping Xiong, Ph.D. (St. Jude), Winfred C. Wang, M.D. (St. Jude and UT); Kenneth Beil, MD (St. Jude); James W. Langston, M.D. (St. Jude and UT); and Kathleen J. Helton, MD (St. Jude and UT). This work was supported by the National Institutes of Health and ALSAC.
St Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit www.stjude.org.
Journal
Radiology