title: Cardiovascular risk assessment in the treatment of nonalcoholic steatohepatitis: a secondary analysis of the MOZART trial.
abstract: BACKGROUND
  Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular risk and mortality. No US Food and Drug Administration (FDA) approved therapies for NASH are available; clinical trials to date have not yet systematically assessed for changes in cardiovascular risk. This study examines the prospective utility of cardiovascular risk assessments, the Framingham risk score (FRS) and coronary artery calcium (CAC) score, as endpoints in a NASH randomized clinical trial, and assesses whether histologic improvements lead to lower cardiovascular risk.
  
  
  METHODS
  Secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial (MOZART) in which 50 biopsy-proven NASH patients received oral ezetimibe 10 mg daily (n = 25) versus placebo (n = 25). Biochemical profiling, FRS, CAC scores, liver biopsies were obtained at baseline and endpoint.
  
  
  RESULTS
  Ezetimibe improved FRS whereas placebo did not (4.4 ± 6.2 to 2.9 ± 4.8, p = 0.038; 3.0 ± 4.4 to 2.9 ± 4.2, p = 0.794). CAC scores did not change with ezetimibe or placebo (180.4 ± 577.2 to 194.1 ± 623.9, p = 0.293; 151.4 ± 448.9 to 183.3 ± 555.7, p = 0.256). Ezetimibe improved FRS and CAC scores in more patients than placebo (48% versus 23%, p = 0.079, and 21% versus 0%, p = 0.090, respectively), though not significantly. No differences were noted in cardiovascular risk scores among histologic responders versus nonresponders.
  
  
  CONCLUSIONS
  Ezetimibe improved FRS whereas placebo did not. FRS and CAC scores improved in a greater proportion of patients with ezetimibe; this trend did not reach significance. These findings indicate the utility and feasibility of monitoring cardiovascular risk in a NASH trial. The utility of CAC scores may be higher in trials of longer duration (⩾52 weeks) and with older patients (age ⩾45). ClinicalTrials.gov registration: NCT01766713.
authors.affiliation: NAFLD Translational Research Unit, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Lin
authors.affiliation: NAFLD Translational Research Unit, Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Ang
authors.affiliation: NAFLD Translational Research Unit, Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hernandez
authors.affiliation: NAFLD Translational Research Unit, Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Ricki
authors.initials: R
authors.lastname: Bettencourt
authors.affiliation: NAFLD Translational Research Unit, Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Jain
authors.affiliation: NAFLD Translational Research Unit, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Joanie
authors.initials: J
authors.lastname: Salotti
authors.affiliation: NAFLD Translational Research Unit, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Richards
authors.affiliation: Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kono
authors.affiliation: NAFLD Translational Research Unit, Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Bhatt
authors.affiliation: Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Hamed
authors.initials: H
authors.lastname: Aryafar
authors.affiliation: Department of Pathology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Lin
authors.affiliation: Department of Pathology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Valasek
authors.affiliation: Department of Pathology and Liver Imaging Group, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Claude B
authors.initials: CB
authors.lastname: Sirlin
authors.affiliation: Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Brouha
authors.affiliation: Professor of Medicine and Associate Director of Clinical Research, Division of Gastroenterology, Adjunct Professor, Division of Epidemiology, University of California at San Diego, Biomedical Research Facility II, 4A18, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
keywords: Framingham risk; coronary artery calcium; fatty liver; hepatic steatosis; score