This Article Full Text Full Text (PDF) Data Supplement Correction (v28,pe14) All Versions of this Article: 27/12/2729    most recent ATVBAHA.107.152298v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fraser, A. Articles by Lawlor, D.A. Search for Related Content PubMed PubMed Citation Articles by Fraser, A. Articles by Lawlor, D.A. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Alcohol Stroke

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2729.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Abigail Fraser; Ross Harris; Naveed Sattar; Shah Ebrahim; George Davey Smith; D.A. Lawlor

From the Department of Social Medicine (A.F., R.H., G.D.S., D.A.L.), University of Bristol, UK; BHF Glasgow Cardiovascular Research Centre (N.S.), University of Glasgow, Scotland; the Department of Epidemiology & Population Health (S.E.), London School of Hygiene & Tropical Medicine, UK; and MRC Centre for Causal Analyses in Translational Epidemiology (G.D.S., D.A.L.), University of Bristol, UK.

Correspondence to Abigail Fraser, Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Rd, Bristol BS8 2PR, UK. E-mail Abigail.Fraser{at}bristol.ac.uk

Objective— To investigate the association of -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.

Key Words: nonalcoholic fatty liver disease • alanine-aminotransferase • -glutamyltransferase • cardiocascular diseases • meta-analysis

This article has been cited by other articles:

				P. Dromparis and E. D. Michelakis A redox-metabolic-electrical remodeling in the diseased left and right ventricle: direct clinical implications in heart disease and beyond. Focus on "Role of {gamma}-glutamyl transpeptidase in redox regulation of K+ channel remodeling in postmyocardial infarction rat hearts" Am J Physiol Cell Physiol, August 1, 2009; 297(2): C231 - C234. [Full Text] [PDF]

				G. Poelzl, C. Eberl, H. Achrainer, J. Doerler, O. Pachinger, M. Frick, and H. Ulmer Prevalence and Prognostic Significance of Elevated {gamma}-Glutamyltransferase in Chronic Heart Failure Circ Heart Fail, July 1, 2009; 2(4): 294 - 302. [Abstract] [Full Text] [PDF]

				K. K. Sato, T. Hayashi, Y. Nakamura, N. Harita, T. Yoneda, G. Endo, and H. Kambe Liver Enzymes Compared With Alcohol Consumption in Predicting the Risk of Type 2 Diabetes: The Kansai Healthcare Study Diabetes Care, June 1, 2008; 31(6): 1230 - 1236. [Abstract] [Full Text] [PDF]

				A. Fraser, N. Sattar, S. Ebrahim, and D.A. Lawlor Is Serum-Glutamylatransferase a Biomarker of Xenobiotics Which Are Conjugated by Glutathione? Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): e29 - e29. [Full Text] [PDF]