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August 17, 2021; 97 (7) Research Article

Sex and Race Differences in the Risk of Ischemic Stroke Associated With Fasting Blood Glucose in REGARDS

Tracy E. Madsen, D. Leann Long, View ORCID ProfileApril P. Carson, George Howard, Dawn O. Kleindorfer, Karen L. Furie, JoAnn E. Manson, View ORCID ProfileSimin Liu, View ORCID ProfileVirginia J. Howard
First published May 27, 2021, DOI: https://doi.org/10.1212/WNL.0000000000012296
Tracy E. Madsen
From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
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D. Leann Long
From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
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April P. Carson
From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
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  • ORCID record for April P. Carson
George Howard
From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
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Dawn O. Kleindorfer
From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
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Karen L. Furie
From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
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JoAnn E. Manson
From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
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Simin Liu
From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
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  • ORCID record for Simin Liu
Virginia J. Howard
From the Departments of Emergency Medicine (T.E.M.), Neurology (K.L.F.), Epidemiology (S.L.), Medicine (S.L.), and Surgery (S.L.), and Center for Global Cardiometabolic Health, Brown University School of Public Health (S.L.), Alpert Medical School of Brown University, Providence, RI; Departments of Biostatistics (D.L.L., G.H.) and Epidemiology (A.P.C., V.J.H.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (D.O.K.), University of Michigan Medical School, Ann Arbor; and Department of Medicine, Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital/Harvard Medical School, Boston, MA.
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  • ORCID record for Virginia J. Howard
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Sex and Race Differences in the Risk of Ischemic Stroke Associated With Fasting Blood Glucose in REGARDS
Tracy E. Madsen, D. Leann Long, April P. Carson, George Howard, Dawn O. Kleindorfer, Karen L. Furie, JoAnn E. Manson, Simin Liu, Virginia J. Howard
Neurology Aug 2021, 97 (7) e684-e694; DOI: 10.1212/WNL.0000000000012296

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Abstract

Objective To investigate sex and race differences in the association between fasting blood glucose (FBG) and risk of ischemic stroke (IS).

Methods This prospective longitudinal cohort study included adults age ≥45 years at baseline in the Reasons for Geographic And Racial Differences in Stroke Study, followed for a median of 11.4 years. The exposure was baseline FBG (mg/dL); suspected IS events were ascertained by phone every 6 months and were physician-adjudicated. Cox proportional hazards were used to assess the adjusted sex/race-specific associations between FBG (by category and as a restricted cubic spline) and incident IS.

Results Of 20,338 participants, mean age was 64.5 (SD 9.3) years, 38.7% were Black, 55.4% were women, 16.2% were using diabetes medications, and 954 IS events occurred. Compared to FBG <100, FBG ≥150 was associated with 59% higher hazards of IS (95% confidence interval [CI] 1.21–2.08) and 61% higher hazards of IS among those on diabetes medications (95% CI 1.12–2.31). The association between FBG and IS varied by race/sex (hazard ratio, FBG ≥150 vs FBG <100: White women 2.05 [95% CI 1.23–3.42], Black women 1.71 [95% CI 1.10–2.66], Black men 1.24 [95% CI 0.75–2.06], White men 1.46 [95% CI 0.93–2.28], pFBG×race/sex = 0.004). Analyses using FBG splines suggest that sex was the major contributor to differences by race/sex subgroups.

Conclusions Sex differences in the strength and shape of the association between FBG and IS are likely driving the significant differences in the association between FBG and IS across race/sex subgroups. These findings should be explored further and may inform tailored stroke prevention guidelines.

Glossary

BMI=
body mass index;
CI=
confidence interval;
FBG=
fasting blood glucose;
HR=
hazard ratio;
IS=
ischemic stroke;
PAF=
population attributable fractions;
REGARDS=
Reasons for Geographic and Racial Differences in Stroke;
SBP=
systolic blood pressure

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received December 23, 2020.
  • Accepted in final form May 7, 2021.
  • © 2021 American Academy of Neurology
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