title: Association between ALT level and the rate of cardio/cerebrovascular events in HIV-positive individuals: the D: A: D study.
abstract: BACKGROUND
  An inverse association between serum alanine aminotransferase (ALT) levels and the risk of myocardial infarction (MI) has been reported in the general population. We investigated associations between ALT levels and the risk of various cardiovascular and cerebrovascular outcomes in a large cohort study of HIV-positive individuals.
  
  
  METHODS
  Using Poisson regression, we investigated associations between the latest ALT level and MI, coronary heart disease (CHD), and stroke, after adjusting for known confounders and cumulative/recent exposure to antiretroviral drugs. Analyses were also performed for the end points of all-cause/liver-related mortality and new-onset diabetes mellitus.
  
  
  RESULTS
  By February 2011, participants had experienced 541 MIs, 804 CHD, and 258 stroke events. The MI rate decreased from 3.1/1000 person-years among those with ALT ≤18 U/L to 2.1/1000 person-years among those with ALT >60 U/L. After adjustment for confounders, each 2-fold increment in ALT was associated with a 19% drop in the MI rate {relative rate, 0.81 [95% confidence interval (CI): 0.74 to 0.89], P = 0.0001}. A weaker inverse association was seen for CHD with no indication of a linear association between ALT levels and stroke (P = 0.72). Adjusted relative rates were 0.88 (95% CI: 0.81 to 0.97) and 0.70 (95% CI: 0.54 to 0.92) in those who were hepatitis C virus negative and hepatitis C virus positive, respectively, and 0.72 (95% CI: 0.58 to 0.89) and 0.84 (0.77 to 0.93) in injection drug users and non-injection drug users, respectively. Liver-related mortality and diabetes both demonstrated a positive association with ALT levels, whereas all-cause mortality showed a U-shaped relationship.
  
  
  CONCLUSIONS
  Higher ALT levels are associated with lower MI risk in HIV-positive individuals, but with higher risks of liver-related mortality and diabetes mellitus.
authors.affiliation: Research Department of Infection and Population Health, UCL, London, United Kingdom. c.sabin@ucl.ac.uk
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: Lene
authors.initials: L
authors.lastname: Ryom
authors.forename: Helen
authors.initials: H
authors.lastname: Kovari
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.forename: Stephane
authors.initials: S
authors.lastname: de Wit
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Francois
authors.initials: F
authors.lastname: Dabis
authors.forename: Christian
authors.initials: C
authors.lastname: Pradier
authors.forename: Wafaa
authors.initials: W
authors.lastname: El-Sadr
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
authors.forename: David
authors.initials: D
authors.lastname: Kamara
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D016001:Confidence Intervals; D003327:Coronary Disease / Q000201:enzymology* / Q000453:epidemiology; D005260:Female; D006679:HIV Seropositivity / Q000201:enzymology* / Q000453:epidemiology; D006526:Hepatitis C / Q000201:enzymology / Q000453:epidemiology; D006801:Humans; D008107:Liver Diseases / Q000201:enzymology* / Q000401:mortality; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology* / Q000453:epidemiology; D016012:Poisson Distribution; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology* / Q000453:epidemiology; D015819:Substance Abuse, Intravenous / Q000201:enzymology / Q000453:epidemiology
chemical_list: D000410:Alanine Transaminase