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Table e-1. Frequency Table of Specific Cancer Types Stratified by the Subsequent Development of a Cerebrovascular Event*†
Cancer Type Total
n=1149
Cerebrovascular Event, n=44‡
No Cerebrovascular Event, n=1105
Prostate 229 (20%) 10 (23%) 219 (20%)
Unknown primary 178 (15%) 11 (25%) 167 (15%)
Lung 146 (13%) 9 (20%) 137 (12%)
Breast 120 (10%) 5 (11%) 115 (10%)
Colorectal 85 (7%) 1 (2%) 84 (8%)
Bladder 53 (5%) 1 (2%) 52 (5%)
Leukemia 42 (4%) 1 (2%) 41 (4%)
Kidney 34 (3%) 2 (5%) 32 (3%)
Non-Hodgkin lymphoma 34 (3%) 1 (2%) 33 (3%)
Melanoma 29 (2%) 0 (0%) 29 (2%)
Pancreas 26 (2%) 0 (0%) 26 (2%)
Primary brain 21 (2%) 0 (0%) 21 (2%)
Ovarian 21 (2%) 0 (0%) 21 (2%)
Head and neck 20 (2%) 0 (0%) 20 (2%)
Multiple myeloma 20 (2%) 2 (5%) 18 (2%)
Thyroid 15 (1%) 0 (0%) 15 (1%)
Uterine 14 (1%) 0 (0%) 14 (1%)
Gastric 13 (1%) 0 (0%) 13 (1%)
Esophageal 9 (1%) 0 (0%) 9 (1%)
Liver 9 (1%) 0 (0%) 9 (1%)
Bone 4 (0%) 0 (0%) 4 (0%)
Hodgkin’s lymphoma 4 (0%) 1 (2%) 3 (0%)
Sarcoma 4 (0%) 0 (0%) 4 (0%)
Gallbladder or biliary tract 3 (0%) 0 (0%) 3 (0%)
Vaginal 3 (0%) 0 (0%) 3 (0%)
Adrenal 2 (0%) 0 (0%) 2 (0%)
Cervical 2 (0%) 0 (0%) 2 (0%)
Penile 2 (0%) 0 (0%) 2 (0%)
Pleura 2 (0%) 0 (0%) 2 (0%)
Small bowel 2 (0%) 0 (0%) 2 (0%)
Endocrine NOS 1 (0%) 0 (0%) 1 (0%)
Primary peritoneal 1 (0%) 0 (0%) 1 (0%)
Thymus 1 (0%) 0 (0%) 1 (0%)
Abbreviations: NOS, not otherwise specified.
*These crude data do not account for differences in follow-up time and censoring between groups.
†Cerebrovascular events were defined as a composite of ischemic or hemorrhagic stroke or transient ischemic attack.
‡Due to rounding, percentages don’t add up to 100.
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Table e-2. Cerebrovascular Event TOAST Classifications Stratified by Diagnosis of Concomitant Cancer*
Classification Total,
n=405†
Cancer, n=40
No Cancer, n=365
Cardioembolism 84 (21%) 12 (30%) 72 (20%)
Large artery atherosclerosis 51 (13%) 6 (15%) 45 (12%)
Small vessel disease 50 (12%) 7 (18%) 43 (12%)
Other determined mechanism 16 (4%) 2 (5%) 14 (4%)
Unknown 204 (50%) 13 (33%) 191 (52%)
Abbreviations: TOAST, Trial of Org 10172 in Acute Stroke Treatment.
*TOAST classifications were only performed in participants with ischemic cerebrovascular events and were missing for 17 events (4% of total participants with ischemic stroke or transient ischemic attack).
†Due to rounding, percentages don’t add up to 100.
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Table e-3. Cox Models Evaluating the Association between a New Cancer Diagnosis and Stroke/TIA:
Sensitivity Analysis Using a Different Outpatient Coding Schema to Identify New Cancer Diagnoses*
Model and Time Period following Cancer Diagnosis† Hazard Ratio (95% CI) Unadjusted
0-30 Days 6.1 (2.7-13.6)
31-90 Days 1.1 (0.3-4.4)
91-180 Days 0.4 (0.1-2.7)
181-365 Days 0.8 (0.3-2.3)
>365 Days 0.9 (0.6-1.3)
Adjustment for demographics, region of residence, and vascular risk factors‡
0-30 Days 6.7 (2.8-16.3)
31-90 Days 1.5 (0.4-5.9)
91-180 Days 0.5 (0.1-3.7)
181-365 Days 0.8 (0.3-2.6)
>365 Days 0.9 (0.6-1.3)
Abbreviations: CI, confidence interval.
*For the primary analysis, new diagnoses of cancer were defined by at least one of the following Medicare claims algorithms: any inpatient or outpatient emergency department claim with International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnoses of 140.xx- 172.xx, 174.xx-208.xx, or 209.0-209.3 in any diagnosis position; any inpatient or outpatient claim with ICD-9-CM, Healthcare Common Procedure Coding System (HCPCS), or Current Procedural
Terminology (CPT ) codes for chemotherapy, radiation, or hormone therapy; or two or more outpatient claims with an ICD-9-CM diagnosis of 140.xx-172.xx, 174.xx-208.xx, or 209.0-209.3 in any diagnosis position associated with physician evaluation and management codes 30 to 365 days apart. In this sensitivity analysis, for those diagnosed through outpatient codes, the date of the first outpatient claim was taken to be the date of cancer diagnosis.
†The proportional hazard assumption was violated for the entirety of patient follow-up. Therefore, hazard ratios were calculated at discrete time periods when the assumption was met.
‡Vascular risk factors included systolic blood pressure, diastolic blood pressure, diabetes mellitus, atrial fibrillation, total and high density cholesterol, coronary heart disease, smoking history, annual income, highest education level, antihypertensive medication use, left ventricular hypertrophy,
estimated glomerular filtration rate, urine albumin-creatinine ratio, physical activity, body mass index, and alcoholic drink consumption.
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Table e-4. Cox Regression Analyses Evaluating the Association between Cancers with Known Metastases (n=322) and Cerebrovascular Events*†
Model and Time Period following Cancer Diagnosis‡ Hazard Ratio (95% CI) Unadjusted
0-30 Days 14.9 (5.6-40.0)
31-90 Days 2.4 (0.3-17.4)
91-180 Days --§
181-365 Days --§
>365 Days 1.6 (0.7-3.9)
Adjustment for demographics, region of residence, and vascular risk factors||
0-30 Days 20.8 (7.7-56.5)
31-90 Days 3.1 (0.4-22.3)
91-180 Days --§
181-365 Days --§
>365 Days 1.3 (0.4-4.1)
Abbreviations: CI, confidence interval.
*For this subgroup analysis, we restricted the cancer exposure to patients with claims for metastatic cancer (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes 196.xx-198.xx, 209.7x).
†Cerebrovascular events were defined as a composite of ischemic or hemorrhagic stroke or transient ischemic attack.
‡The proportional hazard assumption was violated for the entirety of patient follow-up. Therefore, hazard ratios were calculated at discrete time periods when the assumption was met.
§Too few data points to calculate a hazard ratio.
||Vascular risk factors included systolic blood pressure, diastolic blood pressure, diabetes mellitus, atrial fibrillation, total and high density cholesterol, coronary heart disease, smoking history, annual income, highest education level, antihypertensive medication use, left ventricular hypertrophy,
estimated glomerular filtration rate, urine albumin-creatinine ratio, physical activity, body mass index, and alcoholic drink consumption.
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Table e-5. Sensitivity Analysis using a Matched Cohort Design to Evaluate the Association between a New Cancer Diagnosis and Cerebrovascular Events*†
Model and Time Period following Cancer Diagnosis‡ Hazard Ratio (95% CI) Unadjusted besides matching factors
0-30 Days 5.4 (2.4-12.5)
31-90 Days 1.0 (0.2-4.0)
91-180 Days 0.4 (0.1-2.6)
181-365 Days 0.8 (0.3-2.1)
>365 Days 0.9 (0.6-1.3)
Additionally adjusted for region of residence and vascular risk factors§
0-30 Days 5.9 (2.3-15.0)
31-90 Days 1.4 (0.3-5.6)
91-180 Days 0.5 (0.1-3.8)
181-365 Days 0.9 (0.3-2.7)
>365 Days 0.9 (0.6-1.5)
Abbreviations: CI, confidence interval.
*Cancer cases were matched in a 1:4 ratio to control participants without cancer by age tertile (≤65 years, 66-75 years, or >75 years), sex (male or female), race (white or black), and highest education level achieved (less than college or some college or higher).
†Cerebrovascular events were defined as a composite of ischemic or hemorrhagic stroke or transient ischemic attack.
‡The proportional hazard assumption was violated for the entirety of patient follow-up. Therefore, hazard ratios were calculated at discrete time periods when the assumption was met. Reference group is participants without a diagnosis of cancer.
§Vascular risk factors included systolic blood pressure, diastolic blood pressure, diabetes mellitus, atrial fibrillation, total and high density cholesterol, coronary heart disease, smoking history, annual income, antihypertensive medication use, left ventricular hypertrophy, estimated glomerular filtration rate, urine albumin-creatinine ratio, physical activity, body mass index, and alcoholic drink
consumption.
