Association of Cirrhosis and Increased Risk of Cardiovascular Events in a VA Patient Population, A Retrospective Cohort Study

Abstract

Background: There is conflicting evidence regarding prevalence and incidence of atherosclerotic cardiovascular disease (ASCVD) in patients with liver cirrhosis. The risk factors associated with ASCVD within this group of patients have not been investigated previously. Methods and Results: This is a retrospective longitudinal study utilizing the Veterans Affairs (VA) Greater Los Angeles Electronic Medical Record of 623 patients with diagnosis of liver disease. We investigated the incidence of ASCVD events and risk factors associated with ASCVD in these patients. We observed an increase in prevalence of ASCVD events in patients with cirrhosis compared to liver disease patients without cirrhosis (19.12% vs 2.46%). Although the cirrhosis group patients were older but, in our Cox-regression model, after adjusting for traditional ASCVD risk factors especially age, cirrhosis remained a major risk factor for ASCVD events with a hazard ratio (HR) of 5.73 (CI: 2.74-12.72). In the subgroup analysis of cirrhosis group, transferrin saturation greater or equal to 40% had 4.27 times higher risk of ASCVD events than lower transferrin saturation. Conclusion: We propose that the liver damage and subsequent decrease in hepcidin production in patients with cirrhosis would cause a major increase in Non-Transferrin-Bound Iron (NTBI) in circulation. Circula-ting NTBI promotes endothelial dysfunction, produces reactive oxygen species (ROS), and exposes important biomolecules, like low density lipoprotein (LDL), to oxidative stress to facilitate atherosclerosis. Accordingly, these epidemiological results provide evidence for further translational investigations to identify factors to mitigate the development of ASCVD.