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August 29, 2023; 101 (9) Research Article

Association Between Ischemic Stroke Subtype and Stroke Severity

The Atherosclerosis Risk in Communities Study

Michelle C. Johansen, Jinyu Chen, Andrea L.C. Schneider, Julia Carlson, Taylor Haight, Kamakshi Lakshminarayan, Shalom Patole, Rebecca F. Gottesman, Josef Coresh, Silvia Koton
First published July 6, 2023, DOI: https://doi.org/10.1212/WNL.0000000000207535
Michelle C. Johansen
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
MD, PhD
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Jinyu Chen
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
MS
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Andrea L.C. Schneider
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
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Julia Carlson
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
MD
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Taylor Haight
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
MD
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Kamakshi Lakshminarayan
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
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Shalom Patole
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
MD
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Rebecca F. Gottesman
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
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Josef Coresh
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
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Silvia Koton
From the Johns Hopkins University School of Medicine (M.C.J.); Johns Hopkins University School of Public Health (J. Chen, J. Coresh), Baltimore, MD; University of Pennsylvania (A.L.C.S.), Philadelphia; University of North Carolina (J. Carlson), Chapel Hill; Virginia Commonwealth University (T.H.), School of Medicine, Richmond; University of Minnesota (K.L., S.P.), Minneapolis; National Institutes of Neurological Disorders and Stroke Intramural Program (R.F.G.), NIH, Bethesda, MD; and Stanley Steyer School of Health Professions (S.K.), Tel Aviv University, Israel.
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Citation
Association Between Ischemic Stroke Subtype and Stroke Severity
The Atherosclerosis Risk in Communities Study
Michelle C. Johansen, Jinyu Chen, Andrea L.C. Schneider, Julia Carlson, Taylor Haight, Kamakshi Lakshminarayan, Shalom Patole, Rebecca F. Gottesman, Josef Coresh, Silvia Koton
Neurology Aug 2023, 101 (9) e913-e921; DOI: 10.1212/WNL.0000000000207535

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Abstract

Background and Objectives Disability after stroke occurs across ischemic stroke subtypes, with a suggestion that embolic strokes are more devastating. Whether this difference is as a result of differences in comorbidities or differences in severity at the time of the stroke event is not known. The primary hypothesis was that participants with embolic stroke would have more severe stroke at the time of admission and a higher risk of mortality, compared with thrombotic stroke participants even with consideration of confounders over time, with a secondary hypothesis that this association would differ by race and sex.

Methods Atherosclerosis Risk in Communities (ARIC) study participants with incident adjudicated ischemic stroke, stroke severity and mortality data, and complete covariates were included. Multinomial logistic regression models determined the association between stroke subtype (embolic vs thrombotic) and admission NIH Stroke Scale (NIHSS) category (minor [≤5], mild [6–10], moderate [11–15], severe [16–20], and very severe [>20]) adjusted for covariates from visits most proximal to the stroke. Separate ordinal logistic models evaluated for interaction by race and sex. Adjusted Cox proportional hazard models estimated the association between stroke subtype and all-cause mortality (through December 31, 2019).

Results Participants (N = 940) were mean age 71 years (SD = 9) at incident stroke, 51% female, and 38% Black. Using adjusted multinomial logistic regression, the risk of having a more severe stroke (reference NIHSS ≤5) was higher among embolic stroke vs thrombotic stroke patients, with a step-wise increase for embolic stroke patients when moving from mild (odds ratio [OR] 1.95, 95% CI 1.14–3.35) to very severe strokes (OR 4.95, 95% CI 2.34–10.48). After adjusting for atrial fibrillation, there was still a higher risk of having a worse NIHSS among embolic vs thrombotic strokes but with attenuation of effect (very severe stroke OR 3.91, 95% CI 1.76–8.67). Sex modified the association between stroke subtype and severity (embolic vs thrombotic stroke, p interaction = 0.03, per severity category, females OR 2.38, 95% CI 1.55–3.66; males OR 1.75, 95% CI 1.09–2.82). The risk of death (median follow-up 5 years, interquartile range 1–12) was also increased for embolic vs thrombotic stroke patients (hazard ratio 1.66, 95% CI 1.41–1.97).

Discussion Embolic stroke was associated with greater stroke severity at the time of the event and a higher risk of death vs thrombotic stroke, even after careful adjustment for patient-level differences.

Glossary

AF=
atrial fibrillation;
ARIC=
Atherosclerosis Risk in Communities;
BMI=
body mass index;
IQR=
interquartile range;
LDL=
low-density lipoprotein;
NIHSS=
NIH Stroke Scale;
OR=
odds ratio

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.

  • Submitted and externally peer reviewed. The handling editor was Editor-in-Chief José Merino, MD, MPhil, FAAN.

  • Received August 9, 2022.
  • Accepted in final form May 4, 2023.
  • Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.
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