Liver Fibrosis is Associated with Ischemic Stroke Risk in Women but not Men: The REGARDS Study.

Background Nonalcoholic fatty liver disease is inconsistently associated with ischemic stroke, with one study suggesting an association in women and not men. The relative importance of liver fibrosis, as opposed to fatty liver, for cardiovascular risk is increasingly appreciated. We hypothesized that advanced liver fibrosis is associated with incident ischemic stroke risk, and especially in women. Methods We performed a case-cohort study in the REasons for Geographic and Racial Differences in Stroke cohort. Black and white individuals aged 45 and older were recruited between 2003 and 2007 and followed for ischemic stroke. The Fibrosis-4 (FIB-4) score and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS) were calculated using baseline data for stroke cases and a cohort random sample; advanced liver fibrosis was classified using validated cutoffs. Cox proportional hazards models were used to estimate hazard ratios (HR) of stroke after adjusting for potential confounders. Sex differences were assessed. Results There were 572 incident ischemic strokes (285 in women) over 5.4 (SD, 2.2) years. Advanced liver fibrosis was not significantly associated with ischemic stroke overall using the FIB-4 (HR 1.44; 95% CI 0.49-4.28) or NFS (HR 1.76; 95% CI 0.67-4.61). However, liver fibrosis was associated with stroke in 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) when using FIB-4. A similar but non-significant sex difference was seen for NFS. Conclusion Advanced liver fibrosis may be associated with a higher risk of ischemic stroke in women but not men.