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June 05, 2018; 90 (23) Article

New diagnosis of cancer and the risk of subsequent cerebrovascular events

Babak B. Navi, George Howard, Virginia J. Howard, Hong Zhao, Suzanne E. Judd, Mitchell S.V. Elkind, Costantino Iadecola, Lisa M. DeAngelis, Hooman Kamel, Peter M. Okin, Susan Gilchrist, Elsayed Z. Soliman, Mary Cushman, Paul Muntner
First published May 4, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005636
Babak B. Navi
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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George Howard
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Virginia J. Howard
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Hong Zhao
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Suzanne E. Judd
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Mitchell S.V. Elkind
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Costantino Iadecola
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Lisa M. DeAngelis
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Hooman Kamel
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Peter M. Okin
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Susan Gilchrist
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Elsayed Z. Soliman
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Mary Cushman
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Paul Muntner
From the Department of Neurology (B.B.N., C.I., L.M.D., H.K.) and Feil Family Brain and Mind Research Institute (B.B.N., C.I., L.M.D., H.K.), Weill Cornell Medicine, New York; Department of Neurology (B.B.N., L.M.D.), Memorial Sloan Kettering Cancer Center, New York, NY; Departments of Biostatistics (G.H., S.E.J.) and Epidemiology (V.J.H., H.Z., P.M.), School of Public Health, University of Alabama at Birmingham; Department of Neurology (M.S.V.E.), Columbia College of Physicians and Surgeons, New York, NY; Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York; Department of Medicine (P.M.O.), Division of Cardiology, Weill Cornell Medicine, New York, NY; Department of Clinical Cancer Prevention (S.G.), MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine (E.Z.S.), Division of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; and Department of Medicine (M.C.), Division of Hematology and Oncology, University of Vermont, Burlington.
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Citation
New diagnosis of cancer and the risk of subsequent cerebrovascular events
Babak B. Navi, George Howard, Virginia J. Howard, Hong Zhao, Suzanne E. Judd, Mitchell S.V. Elkind, Costantino Iadecola, Lisa M. DeAngelis, Hooman Kamel, Peter M. Okin, Susan Gilchrist, Elsayed Z. Soliman, Mary Cushman, Paul Muntner
Neurology Jun 2018, 90 (23) e2025-e2033; DOI: 10.1212/WNL.0000000000005636

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Abstract

Objective We aimed to evaluate the association between cancer and cerebrovascular disease in a prospective cohort study with adjudicated cerebrovascular diagnoses.

Methods We analyzed participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were 45 years and older and had Medicare coverage for 365 days before their baseline study visit. Participants with a history of cancer or cerebrovascular events were excluded. The time-dependent exposure was a new diagnosis of malignant cancer identified through Medicare claims algorithms. Participants were prospectively followed from their baseline study visit (2003–2007) through 2014 for the outcome of a neurologist-adjudicated cerebrovascular event defined as a composite of stroke (ischemic or hemorrhagic) or TIA. Cox regression was used to evaluate the association between a new cancer diagnosis and subsequent cerebrovascular events. Follow-up time was modeled in discrete time periods to fulfill the proportional hazard assumption.

Results Among 6,602 REGARDS participants who met eligibility criteria, 1,149 were diagnosed with cancer during follow-up. Compared to no cancer, a new cancer diagnosis was associated with subsequent cerebrovascular events in the first 30 days after diagnosis (hazard ratio 6.1, 95% confidence interval 2.7–13.7). This association persisted after adjustment for demographics, region of residence, and vascular risk factors (hazard ratio 6.6, 95% confidence interval 2.7–16.0). There was no association between cancer diagnosis and incident cerebrovascular events beyond 30 days. Cancers considered high risk for venous thromboembolism demonstrated the strongest associations with cerebrovascular event risk.

Conclusion A new diagnosis of cancer is associated with a substantially increased short-term risk of cerebrovascular events.

Glossary

CI=
confidence interval;
HR=
hazard ratio;
ICD-9-CM=
International Classification of Diseases, Ninth Revision, Clinical Modification;
IQR=
interquartile range;
REGARDS=
Reasons for Geographic and Racial Differences in Stroke;
WHO=
World Health Organization

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.

  • CME Course: NPub.org/cmelist

  • Received September 18, 2017.
  • Accepted in final form March 22, 2018.
  • © 2018 American Academy of Neurology
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