Association of Increased Risk of Atherosclerotic Cardiovascular (ASCVD) Event in Chronic Liver Disease Patients with and Without Cirrhosis

Introduction: The current data on the association of advanced liver disease with ASCVD outcomes is conflicting. Hypothesis: Hyperinflammatory state due to decrease in bioavailability of nitric oxide, gut hyperpermeability, recurrent infection causing persistent immune system deregulation in advanced liver disease could increase the risk of development and progression of ASCVD. Method: Our cohort included 486,887 patients with diagnosis of non-alcoholic fatty liver disease, or viral hepatitis liver disease from VA National Database from January 1, 2000 to December 31, 2019. Cohort then further divided into patients with diagnosis of cirrhosis and without cirrhosis. Cox models were used to estimate the association between severity of liver disease (defined as cirrhosis vs no cirrhosis) with time to the first ASCVD event hospitalization defined as myocardial infarction (MI), ischemic stroke (CVA). Model was adjusted for age, sex, hypertension (HTN), diabetes (DM) and smoking history, systolic and diastolic blood pressure (BP), Low Density lipoprotein (LDL) and high- density lipoprotein (HDL). Results: The cohort included 4.6% female, 21% African American, 12% diabetes and 23.5% HTN. The prevalence of HTN and DM were higher in patients with cirrhosis but LDL and systolic BP were much lower in cirrhosis. The time to ASCVD event was 37 vs 73 months in cirrhosis vs no cirrhosis. The Kaplan Meier curve for composite ASCVD is shown in figure 1. In a fully adjusted model, risk of first ASCVD hospitalization was 9% higher in patients with cirrhosis (HR: 1.09, 95%confidence interval, CI (1.07-1.11)). In individual event analysis, risk of time to the first MI and CVA hospitalization were also higher in cirrhosis, with HR 1.01 and 1.20 respectively as shown in figure 1. Conclusion: As liver disease advances to cirrhosis the risk of ASCVD events increases and time to the first ASCVD decreases. The inflammatory state of advanced liver disease could be a possible explanation.