reported online June 5 in JAMA Neurology.
Cirrhosis is known to be associated with “extrahepatic hemorrhagic and thrombotic processes, such as GI bleeding and venous thromboembolism. [But] the cerebrovascular complications of cirrhosis are comparatively less well understood.” Previous studies of the association with stroke have been small and have yielded conflicting results, with some finding a reduced incidence of stroke and others finding an increase among cirrhosis patients, said Neal S. Parikh, MD, of the Fell Family Brain and Mind Research Institute and Weill Cornell Medicine, both in New York, and his associates.
They examined a possible association in a retrospective study involving 1,618,059 Medicare beneficiaries hospitalized during a 6-year period. This included 15,586 patients (1%) who had cirrhosis at baseline. A total of 77,268 developed stroke during a mean of 4.3 years of follow-up. The overall incidence of stroke was 2.17% per year among patients with cirrhosis, compared with only 1.11% per year among those 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, 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, Dr. Parikh and his associates said (JAMA Neurol. 2017 Jun 5 [doi: 10.1001/jamaneurol.2017.0923).
This study was not designed to explore the reasons for an association between cirrhosis and stroke, but the investigators noted many 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 investigators said.