Alanine aminotransferase—a marker of cardiovascular risk at high and low activity levels
Alanine aminotransferase (ALT) plays a crucial role in amino acid metabolism and gluconeogenesis. Serum ALT activity is a reliable marker of liver disease and general health. Serum ALT may be associated with cardiovascular disease (CVD) or mortality and positive, negative, neutral and J- or U-shaped relationships between ALT and CVD or mortality have been reported. A positive or U-shaped relationship between ALT and CVD or mortality appears to be more likely in studies including subjects across all ALT levels. An inverse relationship between ALT and CVD or mortality is more likely in studies including subjects with ALT within the reference range. The association between ALT and CVD or mortality may differ according to age (more likely to be positive in younger and inverse in older subjects), sex (stronger in men), diabetes (more likely to be positive in diabetic subjects and inverse in nondiabetic subjects), obesity (stronger association in lean subjects) and geographic location (stronger association in Asian population). The association between high ALT and CVD or mortality is explained by CVD risk factors (mostly due to underlying hepatic inflammation or nonalcoholic fatty liver disease) that are more prevalent in subjects with high ALT. The association between low ALT and CVD risk is explained by risk factors (advanced age, hepatic aging, frailty, sarcopenia, malnutrition and occult diseases) that tend to cluster in subjects with low ALT levels and are poorly linked with traditional CVD risk factors. High and low ALT levels have clinical meaning and both of them should be reported and analyzed.