Association of sickle cell trait with ischemic stroke among African americans a meta-analysis

Hyacinth I. Hyacinth, Cara L. Carty, Samantha R. Seals, Marguerite R. Irvin, Rakhi Prakash Naik, Gregory L. Burke, Neil A. Zakai, James G. Wilson, Nora Franceschini, Cheryl A. Winkler, Victor A. David, Jeffrey B. Kopp, Suzanne E. Judd, Robert J. Adams, W. T. Longstreth, Leonard Egede, Daniel T. Lackland, Herman Taylor, Jo Ann E. Manson, Virginia Howard & 8 others Matthew Allison, Beatrice E. Gee, Adolfo Correa, Monika M. Safford, Donna K. Arnett, George Howard, Alexander P. Reiner, Mary Cushman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)802-807
Number of pages6
JournalJAMA Neurology
Volume75
Issue number7
DOIs
StatePublished - Jul 1 2018

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Sickle Cell Trait
African Americans
Meta-Analysis
Stroke
Exome

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Hyacinth, H. I., Carty, C. L., Seals, S. R., Irvin, M. R., Naik, R. P., Burke, G. L., ... Cushman, M. (2018). Association of sickle cell trait with ischemic stroke among African americans a meta-analysis. JAMA Neurology, 75(7), 802-807. https://doi.org/10.1001/jamaneurol.2018.0571

Association of sickle cell trait with ischemic stroke among African americans a meta-analysis. / Hyacinth, Hyacinth I.; Carty, Cara L.; Seals, Samantha R.; Irvin, Marguerite R.; Naik, Rakhi Prakash; Burke, Gregory L.; Zakai, Neil A.; Wilson, James G.; Franceschini, Nora; Winkler, Cheryl A.; David, Victor A.; Kopp, Jeffrey B.; Judd, Suzanne E.; Adams, Robert J.; Longstreth, W. T.; Egede, Leonard; Lackland, Daniel T.; Taylor, Herman; Manson, Jo Ann E.; Howard, Virginia; Allison, Matthew; Gee, Beatrice E.; Correa, Adolfo; Safford, Monika M.; Arnett, Donna K.; Howard, George; Reiner, Alexander P.; Cushman, Mary.

In: JAMA Neurology, Vol. 75, No. 7, 01.07.2018, p. 802-807.

Research output: Contribution to journalArticle

Hyacinth, HI, Carty, CL, Seals, SR, Irvin, MR, Naik, RP, Burke, GL, Zakai, NA, Wilson, JG, Franceschini, N, Winkler, CA, David, VA, Kopp, JB, Judd, SE, Adams, RJ, Longstreth, WT, Egede, L, Lackland, DT, Taylor, H, Manson, JAE, Howard, V, Allison, M, Gee, BE, Correa, A, Safford, MM, Arnett, DK, Howard, G, Reiner, AP & Cushman, M 2018, 'Association of sickle cell trait with ischemic stroke among African americans a meta-analysis', JAMA Neurology, vol. 75, no. 7, pp. 802-807. https://doi.org/10.1001/jamaneurol.2018.0571
Hyacinth, Hyacinth I. ; Carty, Cara L. ; Seals, Samantha R. ; Irvin, Marguerite R. ; Naik, Rakhi Prakash ; Burke, Gregory L. ; Zakai, Neil A. ; Wilson, James G. ; Franceschini, Nora ; Winkler, Cheryl A. ; David, Victor A. ; Kopp, Jeffrey B. ; Judd, Suzanne E. ; Adams, Robert J. ; Longstreth, W. T. ; Egede, Leonard ; Lackland, Daniel T. ; Taylor, Herman ; Manson, Jo Ann E. ; Howard, Virginia ; Allison, Matthew ; Gee, Beatrice E. ; Correa, Adolfo ; Safford, Monika M. ; Arnett, Donna K. ; Howard, George ; Reiner, Alexander P. ; Cushman, Mary. / Association of sickle cell trait with ischemic stroke among African americans a meta-analysis. In: JAMA Neurology. 2018 ; Vol. 75, No. 7. pp. 802-807.
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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.",
author = "Hyacinth, {Hyacinth I.} and Carty, {Cara L.} and Seals, {Samantha R.} and Irvin, {Marguerite R.} and Naik, {Rakhi Prakash} and Burke, {Gregory L.} and Zakai, {Neil A.} and Wilson, {James G.} and Nora Franceschini and Winkler, {Cheryl A.} and David, {Victor A.} and Kopp, {Jeffrey B.} and Judd, {Suzanne E.} and Adams, {Robert J.} and Longstreth, {W. T.} and Leonard Egede and Lackland, {Daniel T.} and Herman Taylor and Manson, {Jo Ann E.} and Virginia Howard and Matthew Allison and Gee, {Beatrice E.} and Adolfo Correa and Safford, {Monika M.} and Arnett, {Donna K.} and George Howard and Reiner, {Alexander P.} and Mary Cushman",
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TY - JOUR

T1 - Association of sickle cell trait with ischemic stroke among African americans a meta-analysis

AU - Hyacinth, Hyacinth I.

AU - Carty, Cara L.

AU - Seals, Samantha R.

AU - Irvin, Marguerite R.

AU - Naik, Rakhi Prakash

AU - Burke, Gregory L.

AU - Zakai, Neil A.

AU - Wilson, James G.

AU - Franceschini, Nora

AU - Winkler, Cheryl A.

AU - David, Victor A.

AU - Kopp, Jeffrey B.

AU - Judd, Suzanne E.

AU - Adams, Robert J.

AU - Longstreth, W. T.

AU - Egede, Leonard

AU - Lackland, Daniel T.

AU - Taylor, Herman

AU - Manson, Jo Ann E.

AU - Howard, Virginia

AU - Allison, Matthew

AU - Gee, Beatrice E.

AU - Correa, Adolfo

AU - Safford, Monika M.

AU - Arnett, Donna K.

AU - Howard, George

AU - Reiner, Alexander P.

AU - Cushman, Mary

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

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