Abstract
Background and purposeLiver disease, particularly non-alcoholic fatty liver disease (NAFLD), is a risk factor for cardiovascular disease, but little is known about its relationship with ischemic stroke.MethodsIn the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of 30,239 American black and white adults, we assessed baseline NAFLD as fatty liver index (FLI) >60, and assessed liver biomarkers aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and the AST/ALT ratio and risk of incident ischemic stroke over 5.8 years using a case-cohort study design.ResultsConsidering 572 strokes and a 1,017-person cohort sample, NAFLD was inversely associated with stroke risk in men (HR: 0.50; 95% CI: 0.26, 0.96), as was being in the highest ALT quintile versus the lowest (HR: 0.39; 95% CI: 0.19, 0.78) and the highest versus lowest GGT quintile (HR: 0.45, 95% CI: 0.24, 0.85), but not in women. Conversely, FLI score above the 90th percentile was associated with increased stroke risk among women (HR: 2.26; 95% CI: 1.14–4.47), but not men. AST was not associated with stroke risk in either sex. AST/ALT ratio >2 was strongly associated with increased stroke risk in whites, but not blacks (HRs: 3.64; 95% CI: 1.42–9.35 and 0.97; 95% CI: 0.45–1.99, respectively; p for interaction = 0.03).ConclusionsThe relationships between NAFLD, liver biomarkers, and ischemic stroke are complex, and sex and race differences we observed require further study and confirmation.
Highlights
Liver dysfunction can contribute to thrombotic cardiovascular disease (CVD) through effects on synthesis of lipoproteins [1], coagulation proteins [2], and inflammation factors [3]
Considering 572 strokes and a 1,017-person cohort sample, non-alcoholic fatty liver disease (NAFLD) was inversely associated with stroke risk in men (HR: 0.50; 95% confidence intervals (CI): 0.26, 0.96), as was being in the highest ALT quintile versus the lowest (HR: 0.39; 95% CI: 0.19, 0.78) and the highest versus lowest GGT quintile (HR: 0.45, 95% CI: 0.24, 0.85), but not in women
fatty liver index (FLI) score above the 90th percentile was associated with increased stroke risk among women (HR: 2.26; 95% CI: 1.14–4.47), but not men
Summary
Liver dysfunction can contribute to thrombotic cardiovascular disease (CVD) through effects on synthesis of lipoproteins [1], coagulation proteins [2], and inflammation factors [3]. Non-alcoholic fatty liver disease (NAFLD), which is the accumulation of fat in the liver not caused by alcohol use, affects 10–46% of people in the United States [6], and is prevalent in people with type 2 diabetes and obesity. It is considered the “hepatic manifestation of the metabolic syndrome” [7], and is associated with an increased risk of CVD [8,9,10]. Non-alcoholic fatty liver disease (NAFLD), is a risk factor for cardiovascular disease, but little is known about its relationship with ischemic stroke
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