title: The inverse relationship between alanine aminotransferase in the normal range and adverse cardiovascular and non-cardiovascular outcomes.
abstract: BACKGROUND
  High serum alanine aminotransferase (ALT) levels have been associated with increased risk of diabetes and with increased mortality, but associations of variations of ALT in the normal range with outcomes have been less well studied.
  
  
  METHODS
  We studied the relationship between ALT, mortality and cardiovascular events in the West of Scotland Coronary Prevention Study (WOSCOPS) and the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trials that explicitly excluded subjects with clinically significant liver damage, plus the Leiden 85-plus, a study of survivors to age 85 years. The associations between ALT and morbidity and mortality outcomes were investigated using Cox proportional hazard models adjusting for a comprehensive panel of cardiovascular risk factors.
  
  
  RESULTS
  In all three study cohorts, ALT displayed an independent inverse relationship with all-cause mortality so that hazard ratios for fourth versus first quarter of ALT were all below 1.0; HRs 0.64 [95% confidence interval (CI) 0.50-0.81], 0.86 (0.73-1.01), 0.66 (0.50-0.87); WOSCOPS, PROSPER, Leiden 85-plus, respectively. In WOSCOPS and PROSPER, ALT was also inversely associated with risk of fatal plus non-fatal cardiovascular events, including coronary heart disease (CHD) events and stroke.
  
  
  CONCLUSIONS
  In three independent populations, ALT in the normal range displayed an inverse relationship with total mortality, cardiovascular events and non-cardiovascular events in middle-to-older aged subjects without evidence of clinically significant liver damage, independent of traditional cardiovascular and other risk factors. These findings indicate that the relationship between ALT and clinical outcomes is more complex than generally appreciated.
authors.affiliation: From the Robertson Centre for Biostatistics, University of Glasgow, Glasgow, Scotland.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lloyd
authors.forename: Heather M
authors.initials: HM
authors.lastname: Murray
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Packard
authors.forename: Brendan
authors.initials: B
authors.lastname: Buckley
authors.forename: Catriona
authors.initials: C
authors.lastname: Barlow
authors.forename: David
authors.initials: D
authors.lastname: Preiss
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Cobbe
authors.forename: David J
authors.initials: DJ
authors.lastname: Stott
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D000924:Anticholesteremic Agents; D008055:Lipids; D000410:Alanine Transaminase