Liver enzyme variability and risk of heart disease and mortality: A nationwide population-based study.

Abstract

Liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT), have been suggested as surrogate markers of various cardiovascular diseases. However, previous studies assessed liver enzymes only once at baseline. We investigated the association between liver enzyme variability and the risk of mortality and cardiovascular outcomes in general population. A total of 6496271 subjects participating in ≥3 health examinations within the previous 5years including the index year (2009-2010) were included. Variability was measured using variability independent of the mean. Cox proportional hazard models adjusting demographic factors, comorbidities, blood pressure, total cholesterol, glomerular filtration rate and baseline liver enzyme level were used. During a median follow-up of 6years, there were 106413 deaths (1.6%), 53385 myocardial infarctions (MI, 0.8%), 65143 atrial fibrillations (AF, 1.0%) and 50139 congestive heart failures (CHF, 0.7%). High variability in AST, ALT and GGT was associated with a higher risk for all-cause mortality, MI, AF and CHF. The degree of association was largest for GGT variability. For the highest quartile of GGT variability relative to the lowest quartile, the hazard ratios (95% confidence intervals) were 1.32 (1.28-1.35) for all-cause mortality, 1.16 (1.11-1.20) for MI, 1.28 (1.18-1.38) for AF and 1.25 (1.20-1.30) for CHF. These findings were consistent regardless of alcohol consumption, body mass index and degree of fatty liver. Sensitivity analysis also revealed similar results. Higher visit-to-visit variability of liver enzymes was an independent predictor of all-cause mortality and cardiovascular events.