New diagnosis of cancer and the risk of subsequent cerebrovascular events

Navi, Babak B.; Howard, George; Howard, Virginia J.; Hong, Zhao; Judd, Suzanne E.; Elkind, Mitchell S.V.; Iadecola, Costantino; DeAngelis, Lisa M.; Kamel, Hooman; Okin, Peter M.; Gilchrist, Susan C.; Soliman, Elsayed Z.; Cushman, Mary; Muntner, Paul

doi:10.1212/wnl.0000000000005636

Cited by 38 publications

(41 citation statements)

References 29 publications

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“…We previously reported that among participants enrolled in the prospective REGARDS cohort study, a diagnosis of cancer was associated with an increased short‐term risk of cerebrovascular events . In this follow‐up study, we found that incident cancer was also an independent short‐term risk factor for ATEs more broadly, defined as fatal/nonfatal myocardial infarction or ischemic stroke.…”

Section: Discussionmentioning

confidence: 53%

“…The exposure of interest was any new diagnosis of cancer during follow‐up except squamous or basal cell skin carcinomas. As in previous studies, new diagnoses of cancer were defined by ≥1 of the following Medicare claims algorithms: any inpatient or outpatient emergency department claim with 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, HCPCS, or CPT codes for chemotherapy, radiation, or hormone therapy; or ≥2 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 E&M codes 30 to 365 days apart . In the algorithm requiring ≥2 outpatient claims, the cancer diagnosis was assigned the date of the second cancer claim.…”

Section: Methodsmentioning

confidence: 99%

“…In this design, participants who developed cancer during follow‐up were matched 1:4 to control participants without cancer by age tertile (≤65 years, 66‐75 years, or >75 years), sex, race, and highest education achieved (less than college or some college or higher). These baseline factors were matched because a prior analysis demonstrated differences in these covariates between participants who did and did not develop cancer during follow‐up . To serve as a matched control, participants had to be cancer free at the time when their matched case was diagnosed with cancer.…”

Section: Methodsmentioning

confidence: 99%

“…History of coronary heart disease was determined through the baseline study interview physician E&M codes 30 to 365 days apart. 12 In the algorithm requiring ≥2 outpatient claims, the cancer diagnosis was assigned the date of the second cancer claim. Prior investigations have reported that Medicare claims data can identify incident cancer with ≥98% specificity.…”

Section: Populationmentioning

confidence: 99%

“…[9][10][11] To address the limitations of prior analyses, we recently published a study using prospectively collected data, including adjudicated stroke diagnoses, from the population-based REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort to confirm that incident cancer, particularly when metastatic, is associated with a substantially increased short-term risk of ischemic or hemorrhagic cerebrovascular events independent of vascular risk factors. 12 In this follow-up analysis, we examined whether incident cancer is also an independent risk factor for arterial thromboembolic events (ATEs) more broadly, which we defined as fatal or nonfatal acute myocardial infarction or ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

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The risk of arterial thromboembolic events after cancer diagnosis

Navi

Howard

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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BackgroundRetrospective studies have reported an association between cancer and arterial thromboembolic event (ATE) risk.ObjectivesWe sought to confirm this in a prospective cohort with adjudicated outcomes.MethodsWe evaluated participants enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study with Medicare coverage for 365 days before their baseline visit (2003‐2007). Medicare claims were used to identify new cancer diagnoses during follow‐up. Using incidence‐density sampling, participants who developed cancer were matched by age, sex, race, and education 1:4 to control participants who had not developed cancer. Participants were prospectively followed through 2015 for an expert‐adjudicated ATE, defined as acute myocardial infarction or ischemic stroke. Cox regression was performed to evaluate the association between incident cancer and subsequent ATE.ResultsIn this analysis, 836 REGARDS participants with incident cancer were matched to 3339 control participants without cancer. In the 30 days after cancer diagnosis, 0.60% (n = 5) of the participants had an ATE; most of these events occurred near the time of cancer diagnosis. After adjustment for demographics, geographic region, and cardiovascular risk factors, compared to the noncancer controls, participants with incident cancer had an increased risk of ATE in the first 30 days after diagnosis (hazard ratio, 5.8; 95% confidence interval, 2.1‐15.9). There was no association between cancer diagnosis and ATE beyond 30 days. Cancers with known metastases and types considered high risk for venous thromboembolism had the strongest associations with ATE.ConclusionsIncident cancer is associated with an increased short‐term risk of ATE independent of vascular risk factors.

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Section: Discussionmentioning

confidence: 53%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The risk of arterial thromboembolic events after cancer diagnosis

Navi

Howard

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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Association Between Intracerebral Hemorrhage and Subsequent Arterial Ischemic Events in Participants From 4 Population-Based Cohort Studies

et al. 2021

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and arterial ischemic disease share risk factors, to our knowledge, but the association between the 2 conditions remains unknown. OBJECTIVE To evaluate whether intracerebral hemorrhage was associated with an increased risk of incident ischemic stroke and myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS An analysis was conducted of pooled longitudinal participant-level data from 4 population-based cohort studies in the United States: the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), the Northern Manhattan Study (NOMAS), and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

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Mechanisms of Ischemic Stroke in Patients with Cancer: A Prospective Study

Navi

Sherman

Genova

et al. 2021

Annals of Neurology

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The objective of this study was to examine the pathophysiology of ischemic stroke with cancer. Methods: We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each. The main group included patients with active solid tumor cancer and acute ischemic stroke. The control groups included patients with acute ischemic stroke only or active cancer only. The patients with stroke-only and patients with cancer-only were matched to the patients with cancer-plus-stroke by age, sex, and cancer type, if applicable. The outcomes were prespecified hematological biomarkers and transcranial Doppler microemboli detection. Hematological biomarkers included markers of coagulation (D-dimer and thrombin-antithrombin), platelet function (P-selectin), and endothelial integrity (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], and soluble vascular cell adhesion molecule-1 [sVCAM-1]). Hematological biomarkers were compared between groups using the Kruskal-Wallis and Wilcoxon Rank-Sum tests. In multivariable linear regression models, we adjusted for race, number of stroke risk factors, smoking, stroke severity, and antithrombotic use. Transcranial Doppler microemboli presence was compared between groups using chi-square tests.Results: Levels of all study biomarkers were different between groups. In univariate between-group comparisons, patients with cancer-plus-stroke had higher levels of D-dimer, sICAM-1, sVCAM-1, and thrombomodulin than both control groups; higher levels of thrombin-antithrombin than patients with cancer-only; and higher levels of P-selectin than patients with stroke-only. Findings were similar in multivariable analyses. Transcranial Doppler microemboli were detected in 32% of patients with cancer-plus-stroke, 16% of patients with stroke-only, and 6% of patients with canceronly (p = 0.005). Interpretation: Patients with cancer-related stroke have higher markers of coagulation, platelet, and endothelial dysfunction, and more circulating microemboli, than matched controls.

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New diagnosis of cancer and the risk of subsequent cerebrovascular events

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

Cited by 38 publications

References 29 publications

The risk of arterial thromboembolic events after cancer diagnosis

The risk of arterial thromboembolic events after cancer diagnosis

Association Between Intracerebral Hemorrhage and Subsequent Arterial Ischemic Events in Participants From 4 Population-Based Cohort Studies

Mechanisms of Ischemic Stroke in Patients with Cancer: A Prospective Study

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