Low Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) Ratio Associated with Increased Cardiovascular Disease and its Risk Factors in Healthy Japanese Population

Aims: This study aimed to evaluate the association between aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and cardiovascular disease, and risk factors in a healthy Japanese population. 
Methods: A retrospective cohort study was conducted at St. Luke’s International Hospital, Tokyo, Japan, between 2005 and 2018. We included all participants who visited the hospital for voluntary health checkups. Our primary outcome was the development of cardiovascular disease, and the secondary outcomes were cardiovascular risk factors. We grouped the participants into quartiles (Qs) according to their baseline AST/ ALT ratios and examined the outcomes of patients in each group. 
Results: 87,740 participants were included in this study. The mean age of the participants was 44.9 years [standard deviation (SD): 12.1], and 43,191 (49.2%) were men. The mean AST and ALT levels were 21.7 IU/L (SD 10.0) and 22.4 IU/L (SD 16.5), respectively, resulting in a mean AST/ALT ratio of 1.1 (0.4). During the median follow-up of 1,829 days (interquartile range 756–3,470), 1,493 (1.7%) participants developed cardiovascular disease, 831 (1%) experienced ischemic heart disease, and 723 (0.8%) experienced strokes. Those in the Q1 AST/ALT ratio group had significantly higher hazard ratios compared to those in the Q3 AST/ ALT ratio group [adjusted hazard ratio (HR)=1.32, 95% confidence interval (CI): 1.12-1.56 for cardiovascular disease; HR=1.36, 95%CI: 1.09-1.68 for ischemic heart disease; HR=1.28, 95%CI: 1.00-1.65 for stroke]. However, those belonging to the Q4 or Q5 AST/ALT ratio groups was not statistically different for primary outcomes compared to the Q3 AST/ALT ratio group. In contrast, the adjusted HRs for all secondary outcomes decreased in a dose-dependent manner as the AST/ALT ratio increased. 
Conclusions: A Q1 AST/ALT ratio was associated with an increased risk of cardiovascular disease compared to the Q3 AST/ALT ratio in the Japanese population, which is in contrast with the Western population. In our study, Q4 or Q5 AST/ALT ratios were not associated with cardiovascular disease compared to the Q3 AST/ ALT ratio. As for cardiovascular risk factors, the risk decreased as the AST/ALT ratio increased.