Abstract WP208: Advanced Liver Fibrosis and Stroke Risk in the REasons for Geographic and Racial Differences in Stroke Study

Abstract

Introduction: Advanced liver fibrosis (ALF), particularly due to nonalcoholic fatty liver disease (NAFLD), is associated with high cardiovascular mortality, but its relationship with stroke is unknown. We hypothesized that ALF is associated with incident stroke risk in a national sample. Methods: We used a case-cohort design to assess the association between ALF and stroke in the REasons for Geographic and Racial Differences in Stroke Study. Participants (n=30,239) were recruited between 2003 and 2007 and outcomes prospectively ascertained over a mean of 4.3 years. We excluded participants with baseline stroke and alcohol abuse. Liver enzymes were measured on baseline samples for cases and a cohort random sample (CRS). The Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS) and the Fibrosis-4 (FIB4) score were calculated using baseline data. ALF and its absence were defined using validated cutoffs for each score; the reference group was individuals without ALF. Outcomes were ischemic stroke and hemorrhagic stroke. Weighted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for effect of ALF on outcomes. Models were adjusted for demographics, stroke risk factors, antithrombotic use, and an age*race interaction term. Interactions of ALF by sex were tested. Results: There were 608 incident strokes (536 ischemic, 72 hemorrhagic) and 959 stroke-free participants in the CRS. The prevalence of ALF was 19.5% when defined by the NFS and 5.1% by FIB4. ALF was not associated with ischemic stroke using the NFS (HR 1.76; 95% CI 0.67-4.61) or FIB4 (HR 1.44; 95% CI 0.49-4.28). Effect modification by sex was not observed for ALF defined by the NFS (P=0.71), but ALF defined by FIB4 was associated with an increased risk of ischemic stroke for women (HR 3.51; 95% CI 1.00-12.34) but not men (HR 0.70, 95% CI 0.16-3.16) (P=0.098 for interaction). Hemorrhagic stroke was too rare to model. Conclusion: In a national cohort, ALF was not associated with ischemic stroke overall, but there was an increased risk among women when ALF was defined using the FIB4 score. Further study in larger cohorts with more direct and precise measures of liver disease is warranted.