Elsevier

Clinica Chimica Acta

Volume 452, 15 January 2016, Pages 155-160
Clinica Chimica Acta

Gamma-glutamyl transferase and prognosis in patients with coronary artery disease

https://doi.org/10.1016/j.cca.2015.11.013Get rights and content

Highlights

  • Gamma-glutamyl transferase (GGT) predicts 3-year mortality in patients with CAD.

  • Elevated GGT activity was associated with cardiac and non-cardiac mortality.

  • Elevated GGT was not associated with nonfatal myocardial infarction or stroke.

  • GGT improved prediction of all-cause and non-cardiac mortality but not cardiac mortality.

Abstract

Background

The association between gamma-glutamyl transferase (GGT) activity and outcome of patients with coronary artery disease (CAD) remains poorly investigated.

Methods

The study included 5501 patients with CAD treated with percutaneous coronary intervention and GGT measurements available. The primary outcome was 3-year mortality.

Results

GGT activity tertiles were: 1st tertile (GGT < 28.10 U/L; n = 1866), 2nd tertile (GGT  28.10 U/L to 49.50 U/L; n = 1804) and 3rd tertile (GG > 49.50 U/L; n = 1831). There were 110 deaths in the 1st, 111 deaths in the 2nd and 216 deaths in the 3rd GGT tertile (mortality estimates, 7.1%, 7.2% and 13.9%; P < 0.001). GGT was independently associated with the increased risk of 3-year all-cause (adjusted hazard ratio [HR] = 1.30, 95% confidence interval [CI] 1.18 to 1.44, P < 0.001), cardiac (HR = 1.21 [1.06–1.39], P = 0.005) and non-cardiac (HR = 1.42 [1.23–1.63], P < 0.001) mortality (all risk estimates calculated per standard deviation increase in the log GGT activity). GGT improved prediction of all-cause (P < 0.001) and non-cardiac mortality (P < 0.001) but not cardiac mortality (P = 0.155).

Conclusions

In patients with CAD, elevated GGT activity is associated with increased risk of 3-year all-cause, cardiac and non-cardiac mortality. GGT provided incremental prognostic information on top of cardiovascular and metabolic risk factors for prediction of all-cause and non-cardiac mortality but not cardiac mortality.

Introduction

Gamma-glutamyl transferase (GGT) is a reliable marker of hepatobiliary disease and alcohol abuse [1]. Over the last 2 decades ample evidence showed that elevated activity of GGT may serve as a risk marker for coronary artery disease (CAD) as well. Epidemiological evidence strongly suggests that elevated activity of circulating GGT is associated with incident CAD [2], [3] and predicts all-cause and cardiovascular mortality in unselected populations [4], [5] and patients with known CAD [6], [7], [8]. Catalytically active GGT is found in atherosclerotic plaques [9] and intra-plaque GGT activity was closely correlated with systemic GGT activity [10] and histological markers of plaque instability [11]. These studies raised the possibility that GGT may be directly involved in atherosclerosis, plaque instability and coronary events. Despite numerous studies on the association of GGT with cardiovascular disease, several areas of uncertainty still remain. First, previous studies have shown that GGT is closely associated with cardiovascular and metabolic risk factors [2], [3], [5], [7]. Nevertheless, it remains unexplored whether GGT provides incremental information on top of the information provided by cardiovascular risk factors regarding mortality prediction [3]. Second, based on the assumption that patients with CAD mostly die from cardiac causes, the association between GGT and non-cardiac mortality has gained little attention in these patients. Evidence available, however, suggests that contribution of non-cardiac mortality to overall mortality among patients with CAD has increased probably due to the increased use and efficacy of secondary prevention strategies. A recent study of patients undergoing PCI has shown that in current era only 36.8% of deaths following PCI are of cardiac origin [12]. Furthermore it has been shown that PCI may abolish prognostic power of GGT [6]. Third, the association of GGT with the extent of coronary atherosclerosis [13], [14] or acute CAD events, in particular nonfatal myocardial infarction [3], [5] remains controversial. The aim of this study was 2-fold: first, we investigated the association between GGT and 3-year prognosis in a large series of patients with angiographic CAD after PCI, and; second, we assessed whether GGT provides incremental prognostic information on top of the information provided by cardiovascular and metabolic risk factors in patients with CAD.

Section snippets

2. 1. Patients

The source sample included 6724 patients with CAD who underwent PCI in our institution between January 2000 and January 2011. To be included in the study, patients had to have angiography-confirmed CAD and GGT activity measurement(s) available. Patients with acute infections, malignancies, hepatobiliary disease or alcohol abuse (n = 971 patients) and those with cardiogenic shock (n = 252 patients) were excluded. Thus 5501 patients were included in this study. Of the 5501 patients included, 2967

3. 1. Baseline data

The study included 5501 patients. Patients were divided into subgroups according to GGT activity tertiles which were: 1st tertile (GGT < 28.10 U/L; n = 1866 patients), 2nd tertile (GGT  28.10 U/L to 49.50 U/L; n = 1804 patients) and 3rd tertile (GGT > 49.50 U/L; n = 1831 patients). Baseline data are shown in Table 1. With the exception of the extent of CAD and clinical presentation all other data differed among patients in different GGT tertiles. All patients received coronary stents. Drug-eluting stents were

4. Discussion

The main findings of this study can be summarized as follows: 1) In patients with CAD, elevated activity of circulating GGT was associated with an increased risk of all-cause, cardiac and non-cardiac mortality. 2) Elevated activity of GGT did not correlate with the extent of angiographic CAD and was not associated with increased risk of nonfatal myocardial infarction, stroke or stent thrombosis over 3 years after PCI. 3) GGT provided prognostic information that was incremental and beyond the

Funding

None.

Conflict of interest

None.

References (23)

  • E. Ruttmann et al.

    Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults

    Circulation

    (2005)
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