Hyacinth I Hyacinth1, Cara L Carty2, Samantha R Seals3, Marguerite R Irvin4, Rakhi P Naik5, Gregory L Burke6, Neil A Zakai7,8, James G Wilson9, Nora Franceschini10, Cheryl A Winkler11, Victor A David11, Jeffrey B Kopp12, Suzanne E Judd4, Robert J Adams13, W T Longstreth14, Leonard Egede15, Daniel T Lackland13, Herman Taylor16, JoAnn E Manson17, Virginia Howard4, Matthew Allison18, Beatrice E Gee19, Adolfo Correa20, Monika M Safford21, Donna K Arnett22, George Howard23, Alexander P Reiner24, Mary Cushman7,8. 1. Aflac Cancer and Blood Disorder Center, Emory Children's Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia. 2. Women's Health Initiative, Fred Hutchinson Cancer Research Center, Seattle, Washington. 3. Department of Mathematics and Statistics, Hal Marcus College of Science and Engineering, University of West Florida, Pensacola. 4. Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham. 5. Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland. 6. Division of Public Health Science, Wake Forest University, Winston-Salem, North Carolina. 7. Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington. 8. Department of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington. 9. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson. 10. Department of Nephrology, University of North Carolina, Chapel Hill. 11. Basic Science Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, National Cancer Institute, Frederick, Maryland. 12. National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 13. Stroke Center, Department of Neurology, Medical University of South Carolina, Charleston. 14. Departments of Neurology and Epidemiology, University of Washington, Seattle. 15. Division of General Internal Medicine, Medical College of Wisconsin, Milwaukee. 16. Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia. 17. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 18. Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California, San Diego. 19. Department of Pediatrics, Morehouse School of Medicine, Atlanta, Georgia. 20. Jackson Heart Study, University of Mississippi Medical Center, Jackson. 21. Division of General Internal Medicine, Weill Cornell Medicine, New York, New York. 22. College of Public Health, University of Kentucky College of Public Health, Lexington. 23. Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham. 24. Fred Hutchinson Cancer Research Center, University of Washington, Seattle.
Abstract
Importance: African Americans and individuals of African ancestry have a higher risk of stroke compared with non-Hispanic white individuals. Identifying the source of this disparity could provide an opportunity for clinical stroke risk stratification and more targeted therapy. Whether sickle cell trait (SCT) is an indicator of increased risk of ischemic stroke among African Americans is still unclear. Objective: To examine whether SCT is associated with a higher risk of incident ischemic stroke among African Americans. Design, Setting, and Participants: This meta-analysis assessed the association of SCT with the risk of incident ischemic stroke. Four large, prospective, population-based studies with African American cohorts were assessed: Jackson Heart Study (September 1, 2005, through December 31, 2012), Multi-Ethnic Study of Atherosclerosis (July 1, 2002, through December 31, 2012), Reasons for Geographic and Racial Differences in Stroke (January 1, 2003, through December 31, 2014), and Women's Health Initiative (October 1, 1998, through December 31, 2012). Using a Cox proportional hazards regression model adjusted for major stroke risk factors, this study estimated the hazard ratio for incident ischemic stroke associated with SCT. Data analysis was performed from July 10, 2016, to February 2, 2017. Interventions or Exposures: Participants' SCT status determined by polymerase chain reaction assay genotyping or a combination of whole-exome sequencing and imputation. Main Outcomes and Measures: Incident ischemic stroke. Results: This meta-analysis included 19 464 African American individuals (1520 with SCT, 17 944 without SCT, and 620 with ischemic stroke) from 4 studies, with a mean (SD) age of 60.0 (13.0) years (5257 [27.0%] men and 14 207 [73.0%] women). No differences were found in the distribution of risk factors for ischemic stroke comparing participants with and those without SCT at study visit 1 in each cohort. The crude incidence of ischemic stroke was 2.9 per 1000 person-years (95% CI, 2.2-4.0 per 1000 person-years) among those with SCT and 3.2 per 1000 person-years (95% CI, 2.7-3.8 per 1000 person-years) among those without SCT. After stroke risk factors were adjusted for, the hazard ratio of incident ischemic stroke independently associated with SCT in the meta-analysis of all 4 cohorts was 0.80 (95% CI, 0.47-1.35; P = .82). The results of the meta-analysis were similar to those of individual cohorts, in which the results were also similar. Conclusions and Relevance: Sickle cell trait may not be associated with incidence of ischemic stroke among African Americans. The results of this study suggest performing a more thorough clinical evaluation of a stroke patient with SCT rather than assuming that SCT is the etiologic factor for the stroke.
Importance: African Americans and individuals of African ancestry have a higher risk of stroke compared with non-Hispanic white individuals. Identifying the source of this disparity could provide an opportunity for clinical stroke risk stratification and more targeted therapy. Whether sickle cell trait (SCT) is an indicator of increased risk of ischemic stroke among African Americans is still unclear. Objective: To examine whether SCT is associated with a higher risk of incident ischemic stroke among African Americans. Design, Setting, and Participants: This meta-analysis assessed the association of SCT with the risk of incident ischemic stroke. Four large, prospective, population-based studies with African American cohorts were assessed: Jackson Heart Study (September 1, 2005, through December 31, 2012), Multi-Ethnic Study of Atherosclerosis (July 1, 2002, through December 31, 2012), Reasons for Geographic and Racial Differences in Stroke (January 1, 2003, through December 31, 2014), and Women's Health Initiative (October 1, 1998, through December 31, 2012). Using a Cox proportional hazards regression model adjusted for major stroke risk factors, this study estimated the hazard ratio for incident ischemic stroke associated with SCT. Data analysis was performed from July 10, 2016, to February 2, 2017. Interventions or Exposures: Participants' SCT status determined by polymerase chain reaction assay genotyping or a combination of whole-exome sequencing and imputation. Main Outcomes and Measures: Incident ischemic stroke. Results: This meta-analysis included 19 464 African American individuals (1520 with SCT, 17 944 without SCT, and 620 with ischemic stroke) from 4 studies, with a mean (SD) age of 60.0 (13.0) years (5257 [27.0%] men and 14 207 [73.0%] women). No differences were found in the distribution of risk factors for ischemic stroke comparing participants with and those without SCT at study visit 1 in each cohort. The crude incidence of ischemic stroke was 2.9 per 1000 person-years (95% CI, 2.2-4.0 per 1000 person-years) among those with SCT and 3.2 per 1000 person-years (95% CI, 2.7-3.8 per 1000 person-years) among those without SCT. After stroke risk factors were adjusted for, the hazard ratio of incident ischemic stroke independently associated with SCT in the meta-analysis of all 4 cohorts was 0.80 (95% CI, 0.47-1.35; P = .82). The results of the meta-analysis were similar to those of individual cohorts, in which the results were also similar. Conclusions and Relevance: Sickle cell trait may not be associated with incidence of ischemic stroke among African Americans. The results of this study suggest performing a more thorough clinical evaluation of a strokepatient with SCT rather than assuming that SCT is the etiologic factor for the stroke.
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Authors: Nemin Chen; Christina Caruso; Alvaro Alonso; Vimal K Derebail; Abhijit V Kshirsagar; A Richey Sharrett; Nigel S Key; Rebecca F Gottesman; Megan L Grove; Jan Bressler; Eric Boerwinkle; B Gwen Windham; Thomas H Mosley; Hyacinth I Hyacinth Journal: eNeurologicalSci Date: 2019-07-22