Background-Serum ␥-glutamyltransferase (GGT) is associated with incident cardiovascular diseases and is a potential risk factor for disease mortality. We investigated the relevance of circulating GGT in chronic heart failure. Methods and Results-From 2000 to 2007 clinical and laboratory variables of 1033 consecutive outdoor patients with heart failure were evaluated. Follow-up (mean, 34.4 months) was available in 998 patients. The end point was defined as death from any cause or heart transplantation. A forward stepwise Cox proportional hazards regression model for sex-stratified data was used. Prevalence of elevated GGT was 42.9% in men (GGT Ͼ65 U/L) and 50.2% in women (GGT Ͼ38 U/L), which was higher than for sex-and age-matched healthy subjects (18.6% in men, 19.2% in women) derived from a large historical control group. GGT was associated with severity of heart failure as assessed by New York Heart Association class, left-ventricular ejection fraction, and amino-terminal pro-B-type natriuretic peptide. The end point was recorded in 302 patients. Compared with the lowest GGT quintile, sex-stratified hazard ratios for patients in the highest quintile were 2.88 (1.99 to 4.17) in the univariate model and 1.87 (1.28 to 2.74) in the adjusted model (PϽ0.001). Corresponding 5-year cumulative event rates were 47% and 74%, respectively. Adjusted hazard ratios for elevated GGT was 2.9 (1.64 to 5.17) for patients in New York Heart Association I/II, and 1.2 (0.75 to 2.05) for patients in New York Heart Association III/IV, respectively (Pϭ0.003, for the GGT-New York Heart Association class interaction). Conclusions-Prevalence of elevated GGT is high in patients with chronic heart failure. The GGT levels are associated with disease severity. Increased GGT is an independent predictor of death or heart transplantation. GGT may provide additional prognostic information, especially in patients with mild heart failure. (Circ Heart Fail. 2009;2:294-302.)

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