New diagnosis of cancer and the risk of subsequent cerebrovascular events

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.

Figure 1. Study eligibility criteria

Flow diagram detailing selection criteria for study participants. REGARDS = Reasons for Geographic and Racial Differences in Stroke.

Figure 2. Cumulative incidence of cerebrovascular events among participants with and without a new diagnosis of cancer

New diagnoses of cancer were modeled as a time-dependent exposure. Participants who developed cancer during study follow-up contributed follow-up time to the noncancer group before their cancer diagnosis and to the cancer group after their diagnosis. Follow-up day 0 refers to the date of the baseline REGARDS study visit for participants without cancer, and to the date of cancer diagnosis for participants who developed cancer. Follow-up was censored when participants experienced stroke or TIA, withdrew from the REGARDS study, left Medicare insurance coverage, or on December 31, 2014. The inset shows the same data on a magnified x-axis up to 360 days of follow-up. REGARDS = Reasons for Geographic and Racial Differences in Stroke.