Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults

Abstract

ObjectiveTo estimate the risk of acute myocardial infarction (AMI) or stroke in adults with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).DesignMatched cohort study.SettingPopulation based, electronic primary healthcare databases before 31 December 2015 from four European countries: Italy (n=1 542 672), Netherlands (n=2 225 925), Spain (n=5 488 397), and UK (n=12 695 046).Participants120 795 adults with a recorded diagnosis of NAFLD or NASH and no other liver diseases, matched at time of NAFLD diagnosis (index date) by age, sex, practice site, and visit, recorded at six months before or after the date of diagnosis, with up to 100 patients without NAFLD or NASH in the same database.Main outcome measuresPrimary outcome was incident fatal or non-fatal AMI and ischaemic or unspecified stroke. Hazard ratios were estimated using Cox models and pooled across databases by random effect meta-analyses.Results120 795 patients with recorded NAFLD or NASH diagnoses were identified with mean follow-up 2.1-5.5 years. After adjustment for age and smoking the pooled hazard ratio for AMI was 1.17 (95% confidence interval 1.05 to 1.30; 1035 events in participants with NAFLD or NASH, 67 823 in matched controls). In a group with more complete data on risk factors (86 098 NAFLD and 4 664 988 matched controls), the hazard ratio for AMI after adjustment for systolic blood pressure, type 2 diabetes, total cholesterol level, statin use, and hypertension was 1.01 (0.91 to 1.12; 747 events in participants with NAFLD or NASH, 37 462 in matched controls). After adjustment for age and smoking status the pooled hazard ratio for stroke was 1.18 (1.11 to 1.24; 2187 events in participants with NAFLD or NASH, 134 001 in matched controls). In the group with more complete data on risk factors, the hazard ratio for stroke was 1.04 (0.99 to 1.09; 1666 events in participants with NAFLD, 83 882 in matched controls) after further adjustment for type 2 diabetes, systolic blood pressure, total cholesterol level, statin use, and hypertension.ConclusionsThe diagnosis of NAFLD in current routine care of 17.7 million patient appears not to be associated with AMI or stroke risk after adjustment for established cardiovascular risk factors. Cardiovascular risk assessment in adults with a diagnosis of NAFLD is important but should be done in the same way as for the general population.

Diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) Is Independently Associated with Cardiovascular Risk in a Large Austrian Screening Cohort

“…This is in concordance with a meta-analysis of pooled studies from European, Asian, and American countries suggesting an independent association of NAFLD with CV risk [10]. However, a British study including 17.7 million patients found that the diagnosis of NAFLD was not associated with increased risk for acute myocardial infarction or stroke after adjustment for established CV risk factors [22]. Nevertheless, in another meta-analysis of Targher et al, patients with NAFLD evidenced an increased risk of fatal and non-fatal CV disease [23].…”

Editorial: re‐thinking cardiovascular risk factors in NAFLD with advanced fibrosis? Authors' reply

“…We acknowledge the heterogenous data in this area and that our study is limited by sample size and follow‐up time, though our cohort had the important strengths of being biopsy‐proven, highly phenotyped and having confirmed clinical end points. While population‐based studies like the one cited have advantages in terms of sample size, they also have limitations, most notably, limited phenotyping, often with a lack of confirmation of diagnosis and endpoints . We similarly believe that larger, multicentre, prospective studies are thus needed to further characterise the relationship between NAFLD and cardiovascular disease and to validate our findings.…”

Non-alcoholic fatty liver disease in patients with inflammatory bowel disease might boost cardiovascular disease burden

“…It should be highlighted that, despite the established knowledge that NAFLD is associated with increased risk for the development of CVD, two recently published large cohort studies provide contradictory results on the monitoring of these patients: one suggests that NAFLD patients should be closely monitored for CVD disease prevention [17], while the other proposes that cardiovascular risk stratification in NAFLD patients should be made in the same way as in the general population [18]. We also know that cardiovascular evaluation is rather conservative for asymptomatic NAFLD patients, based on current recommendations, unless they feature intermediate or high risk or have progressed to NASH cirrhosis [19].…”