Nonalcoholic Fatty Liver Disease and Acute Ischemic Stroke

To the Editor: Nonalcoholic fatty liver disease is associated with a higher risk of self-reported cardiovascular disease.1 A recent systematic review also found persons with nonalcoholic fatty liver disease to have a 13% relative increase in carotid intima-media thickness.2 The risk of acute ischemic stroke in relation to inflammatory markers of nonalcoholic fatty liver disease remains unknown. We conducted a cross-sectional records-based study at the London Health Sciences Centre in London, Ontario. We included adults aged 20 to 75 years with suspected acute stroke between January 2005 and December 2009; had all undergone diffusion-weighted magnetic resonance imaging (MRI), which is sensitive and specific for early changes of acute ischemic stroke. Persons with an acute ischemic stroke were considered cases, and those whose scan was negative served as controls. Study entry required that a patient have had serum alanine aminotransferase and aspartate aminotransferase concentrations measured within 90 days before, or within 72 hours after, the MRI. Patients with evidence of intracranial hemorrhage or malignancy on MRI were excluded. The primary study outcome was biochemical evidence of inflammatory nonalcoholic fatty liver disease, defined as an elevated serum alanine aminotransferase concentration ≥95th percentile among the controls. The study was done in accordance with a research protocol approved through the Research Ethics Boards of the London Health Sciences Centre. We included 103 cases with, and 200 controls without, acute stroke, confirmed by diffusion-weighted imaging MRI. Details of participant characteristics are listed in the eAppendix (https://links.lww.com/EDE/A443). Transaminases were measured within a median of 2 days (cases) and 17 days (controls) of the diffusion-weighted imaging MRI. The adjusted odds ratio (OR) for acute stroke in the presence of an elevated alanine aminotransferase was 3.3 (95% confidence interval [CI] = 1.3–8.4) (Table). Similar elevations were observed for as partate aminotransferase concentration, as well as for alanine aminotransferase or aspartate aminotransferase in conjunction with an aspartate aminotransferase:alanine aminotransferase ratio under 2.0 (Table).TABLE: Risk of Stroke Associated With Biochemical Markers of Inflammatory Nonalcoholic Fatty Liver DiseaseA study strength was the inclusion of both cases and controls who underwent sensitive diffusion-weighted MRI imaging for the assessment of acute stroke. This likely reduced the presence of diagnostic suspicion or referral bias,3 and correctly assigned persons with acute stroke as cases and those without acute stroke as controls. Second, we adjusted for a number of stroke risk factors, but not serum triglycerides or hepatic fat on imaging studies.1,4 Others have observed nonalcoholic fatty liver disease to predict the future risk of cardiovascular disease independent of metabolic syndrome.1,4 Among 1221 healthy Japanese men and women, the adjusted OR was 4.1 (95% CI = 1.6–11), but there were only 22 cardiovascular events, of which 12 were self-reported ischemic strokes.4 In a second study of 248 diabetic cases with cardiovascular disease, including just 29 nonfatal ischemic strokes, the associated OR between non alcoholic fatty liver disease and cardiovascular disease was 1.5 (95% CI =1.1–1.7).1 Our study, which focused exclusively on acute ischemic stroke, complements these findings. Confirmatory data are needed regarding whether nonalcoholic fatty liver disease is an independent risk factor for ischemic stroke. If so, then measurement of alanine aminotransferase or aspartate aminotransferase—both of which are readily available and inexpensive—could be considered along with traditional stroke risk factors such as serum glucose, lipids, and blood pressure. Ivan Ying Department of Medicine Schulich School of Medicine and Dentistry London Health Sciences Center University of Western Ontario London, Ontario Gustavo Saposnik Division of Neurology Department of Medicine St. Michael's Hospital University of Toronto Toronto, Ontario Marian J. Vermeulen Institute for Clinical Evaluative Sciences University of Toronto Toronto, Ontario Andrew Leung Department of Medical Imaging Schulich School of Medicine and Dentistry London Health Sciences Centre University of Western Ontario London, Ontario Joel G. Ray Departments of Medicine, Obstetrics and Gynecology Health Policy Management and Evaluation St. Michael's Hospital University of Toronto Toronto, Ontario [email protected]

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