Abstract 14043: Association of Non-Alcoholic Steatohepatitis Assessed by Fib-4 Index and Risk of Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Introduction: Cardiovascular disease (CVD) is the most common cause of death in nonalcoholic steatohepatitis (NASH). While these conditions share many cardio-metabolic risk factors including metabolic syndrome, diabetes and dyslipidemia, limited data exist on whether NASH is independently and prospectively associated with incident CVD beyond traditional risk factors. Fibrosis-4 (FIB-4) index is a scoring system based on platelet count, age, AST and ALT, shown to be comparable to magnetic resolution elastography for predicting advanced fibrosis in biopsy-proven NASH. We sought to evaluate the association of elevated FIB-4 with global CVD events and CVD mortality in the Atherosclerosis Risk in Communities (ARIC) Study Methods: We studied 5531 individuals, mean age of 76 (SD 5.2) years, 58% female, 22% black, at ARIC visit 5 (2011-2013). FIB-4 was categorized as low risk of advanced fibrosis for score <1.45, intermediate for 1.45-3.25 and high for >3.25. Cox regression was used to estimate the association of FIB-4 with time to first global CVD event (CHD, ischemic stroke or heart failure hospitalization) and CVD mortality adjusted for pooled cohort equation risk factors. Results: Over a median follow up of 6.2 (5.3-6.8) years, there were 1108 global CVD events and 457 CVD deaths. In adjusted models, compared to participants with low FIB-4 (<1.45), those with elevated FIB-4 >3.25, had significantly increased risk for global CVD events (HR 1.58, 95% CI 1.23-2.02) and CVD mortality (HR 1.70, 95% CI 1.16-2.50). Conclusions: In a large prospective cohort, presence of advanced liver fibrosis, as assessed by elevated FIB-4 index >3.25, was associated with increased risk for CVD events and CVD mortality, beyond traditional CVD risk factors. Future clinical trials of candidate medications under study for NASH should examine whether effective NASH treatment will impact CV outcomes.