title: Safety and impact on cardiovascular events of long-term multifactorial treatment in patients with metabolic syndrome and abnormal liver function tests: a post hoc analysis of the randomised ATTEMPT study.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS), is common and accounts for 80% of cases of elevated liver function tests (LFTs). We assessed the long-term effects of multifactorial intervention on LFTs and their association with cardiovascular disease (CVD) events in patients with MetS without diabetes mellitus or CVD.
  
  
  METHODS
  This prospective, randomized, open label study included 1,123 patients (aged 45-65 years). Patients received intensive lifestyle intervention and pharmacotherapy: atorvastatin in all patients (low density lipoprotein cholesterol [LDL-C] targets of<100 mg/dl [group A] or<130 mg/dl [group B]), inhibitors of the renin-angiotensin-aldosterone axis for hypertension, metformin for dysglycaemia and orlistat for obesity.
  
  
  RESULTS
  Among participants, 326 had modestly elevated LFTs and ultrasonographic (US) evidence of NAFLD (165 patients in group A2 and 161 patients in group B2). The NAFLD resolved during the 42-month treatment period in 86% of patients in group A2 and in 74% of patients in group B2 (p<0.001). In both groups nearly 90% of patients attained lipid goals. Mean LDL-C and TG levels were higher in group B2 than in group A2 (p<0.001). There were no CVD events in group A2 whereas 5 non-fatal events occurred in group B2 (log-rank-p = 0.024). There were no major side-effects.
  
  
  CONCLUSIONS
  Attaining multiple treatment targets is safe and beneficial in primary prevention patients with MetS and NAFLD. Lipid levels and LFTs normalized, US findings associated with NAFLD resolved and no CVD events occurred in patients with LDL-C levels<100 mg/dl (group A2). Resolution of NAFLD might have contributed to the prevention of CVD events.
authors.affiliation: 2  Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.
authors.forename: Vassilios G
authors.initials: VG
authors.lastname: Athyros
authors.forename: Olga
authors.initials: O
authors.lastname: Giouleme
authors.forename: Emmanouel S
authors.initials: ES
authors.lastname: Ganotakis
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tziomalos
authors.forename: Themistoklis
authors.initials: T
authors.lastname: Vassiliadis
authors.forename: Evangelos N
authors.initials: EN
authors.lastname: Liberopoulos
authors.forename: Eleni
authors.initials: E
authors.lastname: Theocharidou
authors.forename: Asterios
authors.initials: A
authors.lastname: Karagiannis
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis