Serum gamma-glutamyl transferase activity: new high-risk criteria in acute coronary syndrome patients?

In acute coronary syndromes (ACS), oxidation and inflammation have very important roles and in-vitro studies have demonstrated that gamma-glutamyl transferase (GGT) participates in such oxidative and inflammatory reactions. We aimed to evaluate the prognostic value of baseline serum GGT activity on the development of major adverse cardiac event (MACE) in the follow-up of the patients with ACS in coronary care unit (CCU), after 1 and 6 month periods. We included 117 patients (mean age: 61.2+/-11.3 years, 93 males) hospitalized in CCU with the diagnosis of ACS. All had baseline serum GGT activity and were free of systemic and hepatobiliary disease. MACE was defined as the composite of mortality from cardiac causes, recurrent hospitalization with ACS and nonfatal recurrent myocardial infarction diagnoses, to need for coronary revascularization during CCU, over 1 and 6 month follow-up periods. During the follow-up of CCU, MACE occurred in 17 (14.5%) patients (two died). Serum GGT activity was significantly higher in the patients with MACE than those free of MACE (P=0.001) and GGT was found as the independent predictor of the development of MACE-CCU [relative hazard: 1.05, 95% confidence interval (CI): 1.01-1.09, P=0.007]. During the follow-up of 1 month, MACE occurred in 23 (20.0%) patients (five died). Serum GGT activity was significantly higher in patients with MACE than those free of MACE (P=0.021) and GGT was found as the independent predictor of the development of MACE-1 month (relative hazard: 1.04, 95% CI: 1.01-1.08, P=0.039). During the follow-up of 6 months, MACE occurred in 24 (21.8%) patients (two died). Again, GGT was significantly higher in patients who developed MACE than those free of MACE (P=0.001) and GGT was found as the independent predictor of the development of MACE-6 months (relative hazard 1.06, 95% CI: 1.03-1.10, P<0.001). Serum GGT activity was found to be an independent predictor of the development of MACE in the patients with ACS during CCU, over 1 and 6 month follow-up periods.

Association between coronary flow reserve and exercise capacity.

INTRODUCTION: Reduced exercise capacity is of clinical importance. Sometimes no corresponding cardiovascular disease can be found to explain this condition. We hypothesized that coronary microvascular dysfunction may have an effect on exercise capacity in patients without apparent cardiovascular disease. METHODS: Fifty patients (33 female, mean age 46.8 ± 12.4 years) without coronary artery or other cardiac disease were enrolled. Coronary microvascular function was evaluated by measurement of coronary flow reserve (CFR) during transthoracic pulsed-wave Doppler echocardiography with pharmacological stress. CFR was calculated as the ratio of hyperemic to baseline peak diastolic velocities after dipyridamole infusion. Exercise capacity was determined by treadmill exercise testing. Exercise time, metabolic equivalent (MET), and Duke treadmill score (DTS) were recorded and compared with the CFR data. RESULTS: CFR was correlated with exercise time (r=0.376, p=0.007), MET (r=0.435, p=0.002) and DTS (r=0.458, p=0.001). Exercise time, MET, and DTS were lower in patients with impaired CFR (<2) than in those with normal CFR (2) (5.3 ± 1.8 min vs. 8.6 ± 2.7 min, p<0.001; 7.3 ± 3.1 vs. 11.4 ± 2.8, p=0.002; -1.75 (-5.9, 5.0) vs. 7.5 (5.2, 9.41), p<0.001; respectively). CFR was lower in patients with MET7 as compared to patients with MET>7 (2.0 ± 0.5 vs. 2.6 ± 0.6, p=0.015). CONCLUSIONS: CFR is associated with exercise capacity. Thus coronary microvascular dysfunction may be a reason for reduced exercise capacity in patients who have no apparent cardiovascular disease.

Effect of family history of type-2 diabetes on coronary flow reserve and it's relationship with insulin resistance: an observational study.

OBJECTIVE: Coronary microvascular function among offspring of patients with diabetes mellitus might be compromised when compared to persons with no first-degree relative with diabetes mellitus. The aim of the study was to evaluate effect of family history of type-2 diabetes on coronary flow reserve. METHODS: In this observational study, we evaluated coronary flow reserve (CFR) via echocardiography of 95 subjects having a biological parent with type-2 diabetes and 34 healthy volunteers without any biological parent with type-2 diabetes. We have analyzed possible association with CFR and homeostasis model assessment - insulin resistance (HOMA-IR). Comparison analyses were made using independent samples t test, Chi-square test and one-way ANOVA. Association of independent variables with CFR was obtained by correlation analysis and stepwise linear regression model including potential confounders. RESULTS: CFR was significantly lower in the positive family history group than in the controls. Moreover, when compared with controls, the subgroup of insulin-sensitive subjects in the positive family history group also had significantly reduced CFR (2.67±0.28 vs. 2.83±0.19; p=0.01). Correlation analysis revealed that CFR was inversely correlated with HOMA-IR, (r=-0.433), fasting glucose (r=-0.331), fasting insulin (r=-0.396), and hemoglobin (Hb)A1c (r=-0.405). When the positive family history group was divided into tertiles of insulin resistance (HOMA-IR <1.3, 1.3-2.6, and >2.6; Groups 1-2, and 3), there was a significant difference in CFR between Groups 1 and 2 and between Groups 1 and 3 (p<0.05 for all). Though statistically not significant, there was also a difference in CFR between Groups 2 and 3. In a linear regression model, only fasting glucose level was independent predictor of CFR (ß=-677; p value =0.001, 95% CI: -0.061 and -0.019). CONCLUSION: Nondiabetic first-degree relatives of patients with type-2 diabetes are at increased risk of developing coronary microvascular dysfunction.

Association between serum gamma-glutamyltransferase activity and carotid intima-media thickness.

Serum gamma-glutamyltransferase (GGT) activity is a marker of oxidative stress and activity is associated with cardiovascular disease. Carotid intima-media thickness (IMT) is a noninvasive predictor of atherosclerosis. We investigated the association between serum GGT activity and carotid IMT. Fifty-five persons who had normal liver function tests were consecutively enrolled. Carotid IMT was evaluated in the right and left common carotid arteries. The averaged values of carotid IMT and serum GGT activity were compared. Serum GGT activity correlated with carotid IMT (r = .396, P = .003). Serum GGT activities were increased in patients with carotid intimal hyperplasia compared with those without intimal hyperplasia (20.3 ± 11.2 vs 34.3 ± 16.1 U/L; P = .001). Serum GGT activity is associated with carotid IMT. This finding supports the concept that elevated serum GGT activity is a marker of atherosclerosis.