Liver cirrhosis was linked to a greater risk for stroke in a large retrospective study, and the association was independent of established cardiovascular risk factors, a research reported.

In the study of nearly 1.3 million individuals in Germany, multivariable analysis showed a 21% higher risk for any cardiovascular event — stroke or myocardial infarction (MI) — among those with versus without cirrhosis (7.7% vs 5.9%; HR 1.209, 95% CI 1.105-1.322), according to Benjamin Maasoumy, MD, of Hannover Medical School in Germany, who presented the findings at the European Association for the Study of the Liver meeting.

But looking at the two components individually revealed a 37% greater risk for stroke in the cirrhosis group, but no higher risk for MI:

• Stroke: 5.1% vs 3.5% (HR 1.373, 95% CI 1.230-1.532)
• MI: 2.8% vs 2.6% (HR 0.972, 95% CI 0.838-1.127)

“The results are important, however they need to be interpreted with caution,” Omar Massoud, MD, PhD, of the Cleveland Clinic in Ohio, told MedPage Today.

“It is possible that the increase in stroke in the cirrhosis group was at least partially related to the patients being older and males,” he noted. “Even if the investigators adjusted for some of these confounders, it remains unclear how much of the increase in stroke is actually related to cirrhosis.”

Maasoumy noted that liver cirrhosis is associated with systemic inflammation and endothelial dysfunction, as well disturbance of hemostasis, which can lead to an increased risk for bleeding. But whether cirrhosis and adverse cardiovascular events are linked remains a point of controversy.

“The question of why there is an increase in stroke incidence in cirrhotic individuals remains to be explained,” Andrew Talal, MD, of the University at Buffalo in New York, told MedPage Today.

“It is also interesting that myocardial infarctions were not associated with cirrhosis,” said Talal, who was not involved in the study. “This may imply that inflammation may not be the causal reason the investigators initially surmised.”

For their population-based study, the researchers retrospectively examined insurance data on 1,290,057 individuals in northern Germany from 2013 to 2019. Of those, 6,517 had cirrhosis. Patients had to be continuously insured and were excluded if they had a cardiovascular-related event in the years leading up to the study period. ICD-10 codes were used to identify those with liver cirrhosis as well as risk factors for cardiovascular events.

Multivariable analysis adjusted for gender, age, and certain cardiovascular risk factors such as alcohol abuse, atherosclerosis, coronary heart disease, chronic renal failure, heart failure, hypertension, tobacco use, obesity, diabetes, and dyslipidemia.

Advanced stage of cirrhosis — evidenced by portal hypertension, esophageal varices, or ascites/hepatic encephalopathy — was not tied to a greater risk for either stroke or MI, the researchers found.

Those with cirrhosis tended to be older than those without (mean 63 vs 56 years), had higher rates of hypertension (60% vs 44%) and diabetes (37% vs 16%), and were more likely to be male (60% vs 45%) and abuse alcohol (40% vs 2%).

“Patients with cirrhosis can have coagulopathy, coronary artery disease, as well as type II diabetes and dyslipidemia, which are all associated with the development of stroke. We monitor these patients closely,” said Arjmand Mufti, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in this study.

Mufti noted that it would have been helpful to see a breakdown by ischemic versus hemorrhagic stroke, and if risk varied by the etiology of the cirrhosis.

As the study used ICD codes, the mechanism of stroke was unknown, said Maasoumy.

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