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 P. 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; Matthew Allison; Beatrice E. Gee; Adolfo Correa; Monika M. Safford; Donna K. Arnett; George Howard; Alexander P. Reiner; Mary Cushman

doi:10.1001/jamaneurol.2018.0571

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 P. 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 HowardMatthew Allison, Beatrice E. Gee, Adolfo Correa, Monika M. Safford, Donna K. Arnett, George Howard, Alexander P. Reiner, Mary Cushman

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

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 language	English
Pages (from-to)	802-807
Number of pages	6
Journal	JAMA Neurology
Volume	75
Issue number	7
DOIs	https://doi.org/10.1001/jamaneurol.2018.0571
State	Published - Jul 2018

Bibliographical note

Publisher Copyright:
© 2018 American Medical Association. All rights reserved.

Funding

The Multi-Ethnic Study of Atherosclerosis (MESA) and the MESA SHARe (SNP Health Association Resource) project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, UL1-TR-000040, and DK063491. The Jackson Heart Study (JHS) is supported and conducted in collaboration with Jackson State University through contracts HHSN268201300049C and HHSN268201300050C, Tougaloo College through contract HHSN268201300048C, and the University of Mississippi Medical Center through contracts HHSN268201300046C and HHSN268201300047C from the NHLBI and the National Institute for Minority Health and Health Disparities. The Women's Health Initiative (WHI) program is funded by the NHLBI, National Institutes of Health (NIH), US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort is supported by cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke. This work was also supported in part with federal funds by contract HHSN26120080001E from the National Cancer Institute, NIH, and by the Intramural Research Program of the NIH and National Cancer Institute, Center for Cancer Research. This research was also supported in part by grants R01 HL080477 (Dr Safford), 3U01 HL117721 (Dr Hyacinth), 1R01 HL138423-01 (Dr Hyacinth), 1K08HL125100 (Dr Naik), K08HL096841 (Dr Zakai), R01 HL136574 (Dr Reiner), R01 HL132947 (Dr Reiner), R01HL130733 (Dr Reiner), R56 DK104806 (Dr Franceschini), and R21 HL123677 (Dr Franceschini) from the NHLBI and Emory Pediatrics HeRO pilot grant 00051285 (Dr Hyacinth). Atherosclerosis (MESA) and the MESA SHARe (SNP Health Association Resource) project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, UL1-TR-000040, and DK063491. The Jackson Heart Study (JHS) is supported and conducted in collaboration with Jackson State University through contracts HHSN268201300049C and HHSN268201300050C, Tougaloo College through contract HHSN268201300048C, and the University of Mississippi Medical Center through contracts HHSN268201300046C and HHSN268201300047C from the NHLBI and the National Institute for Minority Health and Health Disparities. The Women’s Health Initiative (WHI) program is funded by the NHLBI, National Institutes of Health (NIH), US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort is supported by cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke. This work was also supported in part with federal funds by contract HHSN26120080001E from the National Cancer Institute, NIH, and by the Intramural Research Program of the NIH and National Cancer Institute, Center for Cancer Research. This research was also supported in part by grants R01 HL080477 (Dr Safford), 3U01 HL117721 (Dr Hyacinth), 1R01 HL138423-01 (Dr Hyacinth), 1K08HL125100 (Dr Naik), K08HL096841 (Dr Zakai), R01 HL136574 (Dr Reiner), R01 HL132947 (Dr Reiner), R01HL130733 (Dr Reiner), R56 DK104806 (Dr Franceschini), and R21 HL123677 (Dr Franceschini) from the NHLBI and Emory Pediatrics HeRO pilot grant 00051285 (Dr Hyacinth).

Funders	Funder number
Tougaloo College	HHSN268201300048C
University of Mississippi Medical Center
National Institutes of Health (NIH)
U.S. Department of Health and Human Services	HHSN268201100004C, U01 NS041588, HHSN268201100003C, HHSN271201100004C, HHSN268201100002C, HHSN268201100046C, HHSN268201100001C
National Heart, Lung, and Blood Institute (NHLBI)	R01HL130733, K08HL096841
National Childhood Cancer Registry – National Cancer Institute	1K08HL125100, R56 DK104806, 1R01 HL138423-01, R21 HL123677, R01 HL136574, R01 HL080477, R01 HL132947, 3U01 HL117721, 00051285
National Institute of Neurological Disorders and Stroke	HHSN26120080001E, U01NS041588
Women's Health Initiative
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
National Institute on Minority Health and Health Disparities (NIMHD)
Mississippi Agricultural and Forestry Experiment Station, Mississippi State University	HHSN268201300046C, HHSN268201300047C
Jackson State University	HHSN268201300050C, HHSN268201300049C
Association for Geographic Information
Respiratory Health Association of Metropolitan Chicago
National Cancer Research Institute
Keyano College
Department of Health and Human Services, State Government of Victoria
Ministry of Education and Science of Ukraine	UL1-TR-001079, UL1-TR-000040, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95160, N01-HC-95169, N01-HC-95159, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, DK063491, HHSN268201500003I
Hellenic Atherosclerosis Society

ASJC Scopus subject areas

Clinical Neurology

Access to Document

10.1001/jamaneurol.2018.0571

Cite this

Hyacinth, H. I., Carty, C. L., Seals, S. R., Irvin, M. R., Naik, R. P., Burke, G. L., Zakai, N. A., Wilson, J. G., Franceschini, N., Winkler, C. A., David, V. A., Kopp, J. B., Judd, S. E., Adams, R. J., Longstreth, W. T., Egede, L., Lackland, D. T., Taylor, H., Manson, J. A. E., ... 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

@article{d0c1fac295b1411f8b75616082382e94,

title = "Association of sickle cell trait with ischemic stroke among African americans a meta-analysis",

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 P.} 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",

year = "2018",

month = jul,

doi = "10.1001/jamaneurol.2018.0571",

language = "English",

volume = "75",

pages = "802--807",

number = "7",

}

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

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 P.

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

Y1 - 2018/7

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

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