ARTICLE IN BRIEF
A team of investigators analyzed two groups of women with sickle cell disease: those who use oral contraceptives versus those who do not. They found a four-fold higher risk of stroke in the first group.
PHILADELPHIA—Can the association between stroke and sickle cell disease be mitigated? Yes, according to an analysis of women with sickle cell disease, investigators reported here at the AAN Annual Meeting in April.
Led by Adnan I Qureshi, MD, FAAN, professor of neurology, neurosurgery, and radiology and executive director of the Zeenat Qureshi Stroke Research Center at the University of Minnesota in Minneapolis, a team of investigators analyzed two groups of women with sickle cell disease: those who use oral contraceptives versus those who do not. They found a four-fold higher risk of stroke in the first group.
“While a higher risk of ischemic stroke has been documented in both women who take oral contraceptives and those who have sickle cell disease, the combination of both factors has not been studied,” Dr. Qureshi told Neurology Today.
“Neurologists need to be aware that oral contraceptive use is not uncommon in women with sickle cell disease,” he added. “Given the four-fold higher risk of ischemic stroke associated with oral contraceptive use in young women [and the significant number of smokers within this group], alternate methods of contraception and cessation of cigarette smoking should be strongly considered.”
The research included a total of 1263 women aged between the ages of 15 and 45, who were enrolled in Phase 1 of Cooperative Study of Sickle Cell Disease from 23 centers across the US.
The baseline examinations for the participants screened for demographics, prior medical history, lab assessments, and clinical data. During an average of 5.2 years of follow-up, routine examinations, measures of organ damage, and collection of acute and chronic complications were also collected. Strokes were classified based on clinical data and MRI.
Twenty-two percent of the women (281) reported use of oral contraceptives. Age did not differ significantly between women using or not using contraceptives, but the history of exchange transfusions (24.2 percent versus 15 percent, p=0.003) and cigarette smoking (24.7 percent versus 18.5 percent, p=0.03) was significantly higher in the women who used oral contraceptives.
After adjusting for age, the rate of incident stroke among women who used oral contraceptives was four times higher than those who did not report use (1.4% versus 0.3%, p= 0.04). Once the investigators adjusted for history of exchange transfusion and cigarette smoking in the women, they found that oral contraceptive use was not significantly associated with rate of ischemic stroke (p= 0.2) or stroke-free survival (p= 0.9).
“The four-fold higher risk of incident stroke associated with use of oral contraceptives in women with sickle cell disease can be mitigated by avoiding cigarette smoking,” the authors concluded. These findings, said Dr. Qureshi, “point to the importance of looking at multiple and underlying risk factors, as well as the interplay between already known risk factors.”
One limitation from this work, he noted, might be the “unmeasured effect of other risk factors that predispose women to ischemic stroke.” The length of time that patients had been on oral contraceptives was also not available to the researchers.
In the future, “there needs to be more research into the factors that contribute to the increased risk of ischemic stroke among women with sickle cell disease,” he said.
The abstract presented data from a unique population of patients with sickle cell disease, said Pierre Fayad, MD, FAAN, professor of neurology and director of the stroke center at the University of Nebraska Medical Center. “This study confirms again the harmful effects of smoking and its impact on risk of stroke across the board, even in patients with a recognized cause of stroke such as sickle cell disease.”
Lori Jordan, MD, PhD, director of the pediatric stroke program and associate director of the pediatric neurology residency program at Vanderbilt University School of Medicine in Nashville, TN, said that these results were not surprising.
Citing a meta-analysis of 16 epidemiological studies published in the Journal of the American Medical Association (JAMA) by Leslie Allison Gillum, MD, MPH, of the University of California – San Francisco and colleagues, Dr. Jordan said that earlier research has shown a small increase in ischemic stroke risk in women using oral contraceptives. According to the JAMA report, “nonsmoking, normotensive woman's annual stroke risk would be expected to increase from 4.4 to 8.5 per 100,000 with use of low estrogen oral contraceptives. Therefore, treatment of 24,000 women with oral contraceptives would lead to only one additional ischemic stroke each year.
“Given this low risk in a presumably healthy population of women, it's not surprising that in a population of women with sickle cell disease with a higher stroke risk primarily related to cerebral vasculopathy, the effect of oral contraceptives [after adjusting for exchange transfusion and cigarette smoking] would be rather small,” she continued.
However, Dr. Jordan warned that the true effect of oral contraceptives might not be detectable in a population of this size (only 1263 women). “While smoking cessation and meticulous treatment for sickle cell disease are the most important factors, the use of oral contraceptives in women with sickle cell disease should be considered on a case by case basis,” she said.
This study also points to the larger need for more research on adults with sickle cell disease, Dr. Jordan said. “In children with sickle cell disease, we have proven strategies for primary stroke prevention. In young adults with sickle cell disease, there is little research to guide neurologists and hematologists regarding stroke prevention and treatment.”