Cirrhosis Associated with Increased Risk of Stroke, Particularly Hemorrhagic Stroke

Findings from a recent study showed that cirrhosis significantly increases an individual’s risk of stroke. The strongest associations were observed for subarachnoid and intracerebral hemorrhage.

The investigators conducted a retrospective cohort study using inpatient and outpatient Medicare claims from January 1, 2008, through December 31, 2014, for a random 5% sample of 1,618,059 patients older than 66 years of age.

The primary outcome of the study was stroke, and the secondary outcomes were ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage—–as defined by validated diagnosis code algorithms.

Published in JAMA Neurology, the results of the study showed that 15,586 patients had cirrhosis, and during a mean follow up of 4.3 years, 77,268 patients were hospitalized with a stroke.

The incidence of stroke was 2.17% per year in patients with cirrhosis and 1.11% per year in patients without cirrhosis. After adjusting for demographic characteristics and stroke risk factors, patients with cirrhosis had a higher risk of stroke.

The association appeared to be greatest for intracerebral hemorrhage (HR 1.9) and subarachnoid hemorrhage (HR 2.4) compared with ischemic stroke (HR 1.3).

“Patients with cirrhosis face an increased risk of stroke, particularly hemorrhagic stroke,” the authors concluded. “These findings in a vascular bed that is independent of portal hypertension may reflect the clinical implications of the mixed coagulopathy observed in cirrhosis.”

Limitations to the study included: the diagnosis code algorithm used to ascertain cirrhosis prioritizes positive predictive value or sensitivity; vascular risk factor ascertainment may be incomplete, although the limitation is expected to be equally present in the control group; relatively few patients had alcohol-related cirrhosis, which may have resulted in the secondary analysis being underpowered; the potential misclassification among outcomes; the results may not be generalizable to younger patients because the analysis was of Medicare beneficiaries; 12.3% of the cohort was censored because of a change in insurance; and the investigators were unable to determine the association of antithrombotic medication use or laboratory derangements with their predictors and outcomes because the Medicare data set used for analysis did not include the data.

The authors noted that further examination into the epidemiology and pathophysiology of the association may yield opportunities for stroke reduction and prevention.