All forms of cirrhosis are associated with an increased risk of stroke, especially hemorrhagic stroke, according to a large, nationally representative cohort study published online ahead of print June 5 in JAMA Neurology.
Cirrhosis is commonly associated with “extrahepatic hemorrhagic and thrombotic processes, such as gastrointestinal bleeding and venous thromboembolism. [But] the cerebrovascular complications of cirrhosis are comparatively less well understood,” said Neal S. Parikh, MD, Resident Physician Neurologist at New York-Presbyterian Hospital in New York City, and colleagues. Previous studies of the association between cirrhosis and stroke have been small and have yielded conflicting results.
To examine the association between cirrhosis and stroke, Dr. Parikh and colleagues conducted a retrospective study that involved 1,618,059 Medicare beneficiaries hospitalized during a six-year period. In all, 15,586 patients (1%) had cirrhosis at baseline, and 77,268 patients developed stroke during a mean of 4.3 years of follow-up. In addition, the overall incidence of stroke was 2.17% per year among patients with cirrhosis, compared with 1.11% per year among patients without cirrhosis. After the data were adjusted to account for stroke risk factors, relevant comorbidities, and demographic traits, the annual incidence of any type of stroke was significantly higher with cirrhosis than without cirrhosis (hazard ratio [HR], 1.4). The association was stronger for intracranial hemorrhage (HR, 1.9) and subarachnoid hemorrhage (HR, 2.4) than for ischemic stroke (HR, 1.3).
The results of several secondary and sensitivity analyses were consistent with those of the primary analysis, regardless of whether the cirrhosis was alcohol-related or the stroke was fatal. The association was strongest among patients who had decompensated cirrhosis and was not evident at all among patients who had mild liver disease, said Dr. Parikh and colleagues.
Although this study was not designed to explore the reasons for an association between cirrhosis and stroke, the investigators noted several possible explanations. First, “cirrhosis is accompanied by a mixed coagulopathy, with potential implications for hemorrhagic and thrombotic processes.” It has been linked to many bleeding complications, including, most recently, cerebral microhemorrhages detectable on brain MRI. In addition, the underlying causes of cirrhosis, including alcohol abuse, hepatitis infection, and metabolic disease, may also contribute to stroke risk.
Alternatively, clinicians caring for patients with cirrhosis “may limit the aggressiveness of stroke prevention”—for example, by limiting antithrombotic medications or statins—because they are mindful of the patient’s increased risk of bleeding and hepatic toxicity, the authors said.
—Mary Ann Moon
Suggested Reading
Parikh NS, Navi BB, Schneider Y, et al. Association between cirrhosis and stroke in a nationally representative cohort. JAMA Neurol. 2017 Jun 5 [Epub ahead of print].