Liver enzymes and risk of cardiovascular disease in the general population: a meta-analysis of prospective cohort studies

Background: Gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), commonly used markers of liver dysfunction, have been implicated with risk of cardiovascular disease (CVD). However, the strength and consistency of their associations in the general population have not been reliably quantified.

Methods: We synthesized available prospective epidemiological data on the associations of baseline levels of GGT, ALT, AST, and ALP with CVD [composite CVD, coronary heart disease (CHD), or stroke outcomes]. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science up to December 2013. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random effects models.

Results: Twenty-nine unique cohort studies with aggregate data on over 1.23 million participants and 20,406 cardiovascular outcomes were included. The pooled fully adjusted RRs (95% CIs) for CVD were 1.23 (1.16-1.29) and 1.08 (1.03-1.14) per 1-standard deviation change in log baseline levels of GGT and ALP levels respectively. There was no evidence of an association of ALT or AST with CVD, however, ALT was somewhat inversely associated with CHD 0.95 (0.90-1.00) and positively associated with stroke 1.01 (1.00-1.02) in stratified analysis. Tests for nonlinearity were suggestive of linear relationships of GGT and ALP levels with CVD risk.

Conclusions: Baseline levels of GGT and ALP are each positively associated with CVD risk and in a log-linear fashion. There may be variations in the associations of ALT with cause-specific cardiovascular endpoints, findings which require further investigation.