Gamma-glutamyltransferase is associated with incident vascular events independently of alcohol intake: analysis of the British Women's Heart and Health Study and Meta-Analysis

Objective— To investigate the association of {gamma}-glutamyltransferase (GGT) with incident CHD and stroke. GGT is a marker of alcohol intake but may also reflect oxidative stress and nonalcoholic fatty liver disease. Alanine aminotransferase (ALT) is the enzyme most closely associated with liver fat content. Methods and Results— Associations of GGT and ALT with incident CHD, stroke, and a combined outcome of CHD or stroke were examined in the British Women’s Heart and Health study (n=2961), and a meta-analysis of population based studies examining these associations was performed. In pooled analyses of fully adjusted results of 10 prospective studies, a change of 1 U/L of GGT was associated with a HR=1.20 (95% CI: 1.02, 1.40) for CHD; a HR=1.54 (95% CI: 1.20, 2.00) for stroke; and HR=1.34 (95% CI: 1.22, 1.48) for CHD or stroke. Heterogeneity was substantially decreased when 2 studies in Asian populations were excluded. In a subgroup of nondrinkers results were similar to the main analysis. Meta analyses of the only 2 studies that examined the association of ALT with incident cardiovascular events found a HR=1.18 (95% CI: 0.99, 1.41) for CHD and a HR=1.10 (95% CI: 0.89, 1.36) for CHD or stroke (combined). Conclusion— GGT is associated with incident vascular events independently of alcohol intake. The mechanisms underlying this association remain unclear and require future study. In a meta-analysis of prospective population based studies, GGT was associated with vascular events even among nondrinkers. ALT was also associated with these outcomes. Therefore it is possible that GGT reflects other biological processes such as oxidative stress or liver steatosis, or lifestyle behaviors that are linked to cardiovascular disease.