Liver Cirrhosis Tied to Increased Stroke Risk

Megan Brooks

March 06, 2017

HOUSTON, Texas — Patients with liver cirrhosis are at increased risk for stroke, particularly hemorrhagic stroke, a new study suggests.

Liver cirrhosis is characterized by a coagulopathy associated with both hemorrhagic and thrombotic complications. However, the risk for stroke in patients with cirrhosis has not been thoroughly assessed, the investigators note.

"Overall, our results challenge the notion that cirrhosis is protective against ischemic stroke and complement growing evidence of an increased risk of hemorrhagic stroke in patients with cirrhosis," Neal S. Parikh, MD, from Weill Cornell Medical College in New York City, and colleagues conclude.

"Future studies should explore whether and to what extent variables such as medication use and laboratory derangements mediate the association between cirrhosis and stroke."

Their results were presented at the International Stroke Conference (ISC) 2017.

For this analysis, the researchers examined Medicare beneficiary claims from 2008 to 2014. Among 1,618,059 people, 15,586 (1.0%) had been diagnosed with liver cirrhosis, defined as the presence of at least two International Classification of Diseases, 9th Revision, Clinical Modification inpatient or outpatient claims for liver cirrhosis or its complications.

Patients with cirrhosis had a mean age of 74.1 years, and 47% were women.

Each year, stroke occurred in 2.2% of those who had liver cirrhosis vs 1.1% in patients without liver cirrhosis, report the researchers.

After adjustment for demographic characteristics and stroke risk factors, patients with liver cirrhosis had a 40% higher risk for stroke relative to their peers without cirrhosis. The association was stronger for intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) than for ischemic stroke.

Table 1. Stroke Risk Associated With Cirrhosis (Hazard Ratios and 95% Confidence Intervals)

Endpoint All Stroke Ischemic Stroke ICH SAH
Cirrhosis 1.4 (1.3 - 1.5) 1.3 (1.2 - 1.5) 1.9 (1.5 - 2.4) 2.4 (1.7 - 3.5)

 

In a separate analysis, the researchers identified individuals with alcohol-related cirrhosis (n = 3255 ), non–alcohol-related cirrhosis (n = 11,164), and decompensated cirrhosis (n = 6043) and found that the risk for stroke, ischemic stroke, ICH, and SAH were consistently elevated relative to the risk in cirrhosis-free individuals.

Table 2. Stroke Risk by Cirrhosis Type (Hazard Ratios and 95% Confidence Intervals)

Cirrhosis Type All Stroke (95% Confidence Interval) Ischemic Stroke ICH SAH
Alcohol-related 1.5 (1.2 - 1.8) 1.4 (1.2 - 1.7) 2.3 (1.5 - 3.7) 1.6 (2.7 - 4.0)
Non–alcohol-related 1.5 (1.3 - 1.4) 1.4 (1.2 - 1.5) 2.1 (1.6 - 2.7) 2.8 (1.9 - 4.1)
Decompensated 1.7 (1.5 - 2.0) 1.6 (1.8 - 3.5) 2.5 (1.8 - 3.5) 2.8 (1.7 - 5.0)

 

"The patients we studied were elderly and had a high burden of vascular risk factors, so the findings can't be generalized necessarily to all patients with liver cirrhosis," Dr Parikh noted in an interview with Medscape Medical News. "But doctors who are taking care of patients with liver cirrhosis, particularly older patients, should manage vascular risk factors appropriately," said Dr Parikh.

A Challenge to Current Thinking

Commenting on the results, Philip Gorelick, MD, medical director of the Hauenstein Neuroscience Center and clinical professor of translational science and molecular medicine at Michigan State University College of Human Medicine, East Lansing, said this study challenges the idea that ischemic stroke doesn't happen in liver cirrhosis and heightens awareness of the risks for hemorrhagic stroke in these patients.

"The clinician in practice is well aware that patients with liver cirrhosis are prone to bleeding as there are pro-hemorrhagic coagulation factor abnormalities associated with liver damage," Dr Gorelick said. "As disease progresses, these patients often languish with hepatic encephalopathy, ascites, and esophageal varices and die due to these complications. Clinicians, however, are less familiar with the anticipated elevated risk of brain hemorrhage and may not expect to encounter ischemic stroke in these patients," he added.

"This large study suggests that the relative risk of ICH and SAH are generally high, especially with far advanced liver cirrhosis, and in addition, there is increased risk of ischemic stroke, though the relative risk is not as high as that for hemorrhagic stroke," he said.

Patients with liver cirrhosis may not receive certain medications that prevent ischemic stroke, including antithrombotics, certain antihypertensive agents, and statin agents, because of concern about bleeding risk or the safety of these medications in these patients, he noted.

"Extrahepatic brain thrombotic complications could be explained at least in part by a lack of preventive treatment, as bleeding and other safety risks may dictate that such therapy is not used," Dr Gorelick concluded.

The study had no funding, and the authors have disclosed no relevant financial relationships. Dr Gorelick is a consultant with BrainsGate.

International Stroke Conference (ISC) 2017. Poster WMP60. Presented February 22, 2017.

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