Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 105788 |
| Journal | Journal of Stroke and Cerebrovascular Diseases |
| Volume | 30 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2021 |
Funding
This research project is supported by cooperative agreement U01 NS041588 co-funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Service. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIA. Representatives of the NINDS were involved in the review of the manuscript but were not directly involved in the collection, management, analysis or interpretation of the data. The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at: https://www.uab.edu/soph/regardsstudy/ . Additional funding was provided by K08HL096841, which included funding for select assays. This research project is supported by cooperative agreement U01 NS041588 co-funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Service. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIA. Representatives of the NINDS were involved in the review of the manuscript but were not directly involved in the collection, management, analysis or interpretation of the data. The authors thank the other investigators, the staff, and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at: https://www.uab.edu/soph/regardsstudy/. Additional funding was provided by K08HL096841, which included funding for select assays.
Keywords
- Epidemiology
- Ischemic Stroke
- Liver disease
- NAFLD
- Risk factors
- Women
ASJC Scopus subject areas
- Surgery
- Rehabilitation
- Clinical Neurology
- Cardiology and Cardiovascular Medicine