Elevated hepatic enzymes and incidence of venous thromboembolism: A prospective study

Purpose: Approximately 10% of the general population has elevated blood concentrations of hepatic enzymes, which are linked to increased coagulation markers. We tested whether elevated hepatic enzymes are associated with increased risk of venous thromboembolism (VTE). Methods: We followed 12,604 adults with measurements of alanine transaminase, aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) prospectively for VTE occurrence. Results: AST and GGT above the laboratory normal values were associated over two decades of follow-up with increased risk of total (n=532) and provoked VTE (n=332), but with not unprovoked VTE (n=200). In a model adjusted for age, race, sex, hormone replacement, alcohol intake, diabetes, body mass index, estimated glomerular filtration rate, and C-reactive protein, the hazard ratios (HR) (95% confidence interval) for high versus normal AST were 1.46 (1.00-2.11) for total VTE and 1.83 (1.21-2.79) for provoked VTE. For high GGT, the HR were 1.34 (1.06-1.69) for total VTE and 1.43 (1.07-1.91) for provoked VTE. When follow-up was limited to the first 10 years, associations were even stronger (HR≈1.7 for total VTE). Conclusions: Elevated concentrations of two hepatic enzymes (AST and GGT) in this general middle-aged population are associated with a modestly increased risk of VTE.