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July 05, 2022; 99 (1) Research Article

Prediction of Hidden Coronary Artery Disease Using Machine Learning in Patients With Acute Ischemic Stroke

JoonNyung Heo, Joonsang Yoo, Hyungwoo Lee, Il Hyung Lee, Jung-Sun Kim, Eunjeong Park, Young Dae Kim, View ORCID ProfileHyo Suk Nam
First published April 25, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200576
JoonNyung Heo
From the Department of Neurology (J.H., H.L., I.H.L., Y.D.K., H.S.N.) and Department of Internal Medicine (J.-S.K.), Division of Cardiology, Yonsei University College of Medicine, Seoul; Department of Neurology (J.Y.), Yonsei University College of Medicine, Yongin Severance Hospital; and Integrative Research Center for Cerebrovascular and Cardiovascular Diseases (E.P.), Seoul, Korea.
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Joonsang Yoo
From the Department of Neurology (J.H., H.L., I.H.L., Y.D.K., H.S.N.) and Department of Internal Medicine (J.-S.K.), Division of Cardiology, Yonsei University College of Medicine, Seoul; Department of Neurology (J.Y.), Yonsei University College of Medicine, Yongin Severance Hospital; and Integrative Research Center for Cerebrovascular and Cardiovascular Diseases (E.P.), Seoul, Korea.
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Hyungwoo Lee
From the Department of Neurology (J.H., H.L., I.H.L., Y.D.K., H.S.N.) and Department of Internal Medicine (J.-S.K.), Division of Cardiology, Yonsei University College of Medicine, Seoul; Department of Neurology (J.Y.), Yonsei University College of Medicine, Yongin Severance Hospital; and Integrative Research Center for Cerebrovascular and Cardiovascular Diseases (E.P.), Seoul, Korea.
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Il Hyung Lee
From the Department of Neurology (J.H., H.L., I.H.L., Y.D.K., H.S.N.) and Department of Internal Medicine (J.-S.K.), Division of Cardiology, Yonsei University College of Medicine, Seoul; Department of Neurology (J.Y.), Yonsei University College of Medicine, Yongin Severance Hospital; and Integrative Research Center for Cerebrovascular and Cardiovascular Diseases (E.P.), Seoul, Korea.
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Jung-Sun Kim
From the Department of Neurology (J.H., H.L., I.H.L., Y.D.K., H.S.N.) and Department of Internal Medicine (J.-S.K.), Division of Cardiology, Yonsei University College of Medicine, Seoul; Department of Neurology (J.Y.), Yonsei University College of Medicine, Yongin Severance Hospital; and Integrative Research Center for Cerebrovascular and Cardiovascular Diseases (E.P.), Seoul, Korea.
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Eunjeong Park
From the Department of Neurology (J.H., H.L., I.H.L., Y.D.K., H.S.N.) and Department of Internal Medicine (J.-S.K.), Division of Cardiology, Yonsei University College of Medicine, Seoul; Department of Neurology (J.Y.), Yonsei University College of Medicine, Yongin Severance Hospital; and Integrative Research Center for Cerebrovascular and Cardiovascular Diseases (E.P.), Seoul, Korea.
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Young Dae Kim
From the Department of Neurology (J.H., H.L., I.H.L., Y.D.K., H.S.N.) and Department of Internal Medicine (J.-S.K.), Division of Cardiology, Yonsei University College of Medicine, Seoul; Department of Neurology (J.Y.), Yonsei University College of Medicine, Yongin Severance Hospital; and Integrative Research Center for Cerebrovascular and Cardiovascular Diseases (E.P.), Seoul, Korea.
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Hyo Suk Nam
From the Department of Neurology (J.H., H.L., I.H.L., Y.D.K., H.S.N.) and Department of Internal Medicine (J.-S.K.), Division of Cardiology, Yonsei University College of Medicine, Seoul; Department of Neurology (J.Y.), Yonsei University College of Medicine, Yongin Severance Hospital; and Integrative Research Center for Cerebrovascular and Cardiovascular Diseases (E.P.), Seoul, Korea.
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  • ORCID record for Hyo Suk Nam
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Prediction of Hidden Coronary Artery Disease Using Machine Learning in Patients With Acute Ischemic Stroke
JoonNyung Heo, Joonsang Yoo, Hyungwoo Lee, Il Hyung Lee, Jung-Sun Kim, Eunjeong Park, Young Dae Kim, Hyo Suk Nam
Neurology Jul 2022, 99 (1) e55-e65; DOI: 10.1212/WNL.0000000000200576

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Abstract

Background and Objectives A machine learning technique for identifying hidden coronary artery disease (CAD) might be useful. We developed and validated machine learning models to predict patients with hidden CAD and to assess long-term outcomes in patients with acute ischemic stroke.

Methods Multidetector coronary CT was performed for patients without a known history of CAD. Primary outcomes were defined as having any degree of CAD and having obstructive CAD (≥50% stenosis). Demographic variables, risk factors, laboratory results, Trial of ORG 10172 in Acute Stroke Treatment classification, NIH Stroke Scale score, blood pressure, and carotid artery stenosis were used to develop and validate machine learning models to predict CAD. Area under the receiver operating characteristic curves (AUC) was calculated for performance analysis, and Kaplan-Meier and Cox survival analyses of long-term outcomes were performed. Major adverse cardiovascular events (MACEs) were defined as ischemic stroke, myocardial infarction, unstable angina, urgent coronary revascularization, and cardiovascular mortality.

Results Overall, 1,710 patients were included for the training dataset and 348 patients for the validation dataset. An extreme gradient boosting model was developed to predict any degree of CAD, which showed an AUC of 0.763 (95% CI 0.711–0.814) on validation. A logistic regression model was used to predict obstructive CAD and had an AUC of 0.714 (95% CI 0.692–0.799). During the first 5 years of follow-up, MACEs occurred more frequently with predictions of any CAD (p = 0.022) or obstructive CAD (p < 0.001). Cox proportional analysis showed that the hazard ratio of MACE was 1.5 (95% CI 1.1–2.2; p = 0.016) with prediction of any CAD, whereas it was 1.9 (95% CI 1.3–2.6; p < 0.001) for obstructive CAD.

Discussion We demonstrated that machine learning may help identify hidden CAD in patients with acute ischemic stroke. Long-term outcomes were also associated with prediction results.

Classification of Evidence This study provides Class II evidence that in patients with acute ischemic stroke with CAD risk factors but no known history of CAD, a machine learning model predicts CAD on multidetector coronary CT with an AUC of 0.763 (95% CI 0.711–0.814).

Glossary

AUC=
area under the receiver operating characteristic curve;
CAD=
coronary artery disease;
HDL=
high-density lipoprotein;
LDL=
low-density lipoprotein;
MACE=
major adverse cardiovascular event;
MDCT=
multidetector coronary CT;
NIHSS=
NIH Stroke Scale;
TOAST=
Trial of ORG 10172 in Acute Stroke Treatment;
XGBoost=
extreme gradient boosting

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 editors were Brad Worrall, MD, MSc, FAAN, and José Merino, MD, MPhil, FAAN.

  • Editorial, page 13

  • Class of Evidence: NPub.org/coe

  • CME Course: NPub.org/cmelist

  • Received October 11, 2021.
  • Accepted in final form March 2, 2022.
  • © 2022 American Academy of Neurology
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