title: Inverse linear associations between liver aminotransferases and incident cardiovascular disease risk: The PREVEND study.
abstract: BACKGROUND
  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been linked with an increased risk of type 2 diabetes, but their relationships with cardiovascular disease (CVD) are uncertain. We aimed to assess the associations of ALT and AST with CVD risk and determine their potential utility for CVD risk prediction.
  
  
  METHODS
  ALT and AST measurements were made at baseline in the PREVEND prospective cohort involving 6899 participants aged 28-75 years without pre-existing CVD.
  
  
  RESULTS
  During 10.5 years of follow-up, 729 CVD events were recorded. Serum aminotransferases were strongly correlated with each other and each weakly correlated with several cardiovascular risk markers. ALT and AST were each approximately log-linearly associated with CVD risk. In analyses adjusted for conventional risk factors, the hazard ratios (95% CIs) for CVD per 1 standard deviation increase in loge ALT and loge AST were 0.87 (0.79-0.94; P = 0.001) and 0.91 (0.84-0.98; P = 0.017) respectively. The associations remained consistent after additional adjustment for several potential confounders including alcohol consumption, fasting glucose, and C-reactive protein, with corresponding hazard ratios of 0.88 (0.80-0.96; P = 0.003) and 0.92 (0.84-0.99; P = 0.029). The inverse associations persisted within normal ranges of the aminotransferases. Adding ALT or AST to a CVD risk prediction model containing established risk factors did not improve the C-index or net reclassification.
  
  
  CONCLUSIONS
  Available data suggest the liver aminotransferases are each inversely, independently, and approximately log-linearly associated with CVD risk. Nonetheless, they provide no significant improvement in CVD risk assessment beyond conventional CVD risk factors.
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; School of Clinical Sciences, University of Bristol, Bristol, United Kingdom. Electronic address: skk31@cantab.net.
authors.forename: Setor K
authors.initials: SK
authors.lastname: Kunutsor
authors.affiliation: Department of Internal Medicine, University of Groningen and University Medical Center, Groningen, The Netherlands; Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Clinical Chemistry, University of Groningen and University Medical Center, Groningen, The Netherlands.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Kootstra-Ros
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center, Groningen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Blokzijl
authors.affiliation: Department of Internal Medicine, University of Groningen and University Medical Center, Groningen, The Netherlands.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Gansevoort
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center, Groningen, The Netherlands.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D002097:C-Reactive Protein; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Alanine aminotransferase; Aspartate aminotransferase; Cardiovascular disease; Risk factor; Risk prediction