title: Nonalcoholic fatty liver disease and the risk of clinical cardiovascular events: A systematic review and meta-analysis.
abstract: OBJECTIVE
  Numerous studies have assessed the association between Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However, results have been conflicting due to variability in definitions of NAFLD and ascertainment of CVD, often combining clinical and surrogate endpoints. We therefore systematically reviewed published literature to assess the association between NAFLD and clinical cardiovascular events (CVE) and performed a meta-analysis.
  
  
  METHODS
  We searched PubMed, Medline, Cochrane, CINAHL, and Web of Science databases using terms "nonalcoholic fatty liver disease", "nonalcoholic steatohepatitis", "cardiovascular disease", and their combinations to identify prospective studies published from inception through March 2016. Data from selected studies was extracted and meta-analysis was then performed using random effects model.
  
  
  RESULTS
  A total of six studies with 25,837 patients (NAFLD: 5953; controls: 19,884) were included in the final analysis. Patients with NAFLD had a significantly higher risk of clinical CVE compared to controls (RR: 1.77; 95% CI: 1.26-2.48, p<0.001). Exclusion sensitivity analysis did not alter the above results. The association remained consistent for subgroups with clinical coronary artery disease (RR: 2.26; 95% CI: 1.04-4.92, p<0.001) and ischemic stroke (RR: 2.09; 95% CI: 1.46-2.98, p<0.001). The risk of cardiovascular mortality was also increased in the NAFLD group (RR 1.46, 95% CI 1.31-1.64, p<0.001).
  
  
  CONCLUSIONS
  NAFLD patients have a significantly higher risk for clinical CVE compared to those without. These results need to be confirmed in large prospective studies.
authors.affiliation: Division of Cardiology, Creighton University School of Medicine, Omaha, NE, USA. Electronic address: toufikmahfoodhaddad@creighton.edu.
authors.forename: Toufik
authors.initials: T
authors.lastname: Mahfood Haddad
authors.affiliation: Division of Gastroenterology/Inflammatory Bowel Disease, McGaw Medical Center of Northwestern University, Chicago, IL, USA.
authors.forename: Shadi
authors.initials: S
authors.lastname: Hamdeh
authors.affiliation: Division of Cardiology, Creighton University School of Medicine, Omaha, NE, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Kanmanthareddy
authors.affiliation: Division of Cardiology, Creighton University School of Medicine, Omaha, NE, USA.
authors.forename: Venkata M
authors.initials: VM
authors.lastname: Alla
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology*; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*
keywords: Cardiovascular disease; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis