-Glutamyltransferase as a Risk Factor for Cardiovascular Disease Mortality: An Epidemiological Investigation in a Cohort of 163 944 Austrian Adults (original) (raw)
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European Heart Journal, 2006
Aims Serum gamma-glutamyltransferase (GGT) concentration may be involved in atherosclerosis. This study examined if serum GGT predicted coronary heart disease (CHD), especially differentiating nonfatal myocardial infarction (MI) and fatal CHD event, among the general population or participants with type-2 diabetes. Methods and results A prospective study of 28 838 Finnish men and women aged 25-74 years was performed (1467 incident CHD cases; a median follow-up time of 11.9 years). Serum GGT cutpoints were the 25th, 50th, 75th, and 90th sex-specific percentiles. After adjustment for known cardiovascular risk factors, compared with the lowest GGT category, hazard ratios (HR) were 1.15, 1.25, 1.27, and 1.57 among men and 1.03, 1.22, 1.32, and 1.44 among women in other four GGT categories (P for trend ,0.01, respectively). However, stronger associations were observed among subjects aged ,60 and among alcohol drinkers. The strength of association was similar for non-fatal MI and for fatal CHD. Among subjects with type-2 diabetes, the corresponding adjusted HRs were 1.29, 1.57, 1.88, and 1.78 (P trend ¼ 0.03, men and women combined). Conclusion This study suggests an independent mechanism linking serum GGT to CHD among general population. Even though the strength of association appeared to be modest among all subjects, stronger associations were observed among subjects aged ,60 and among alcohol drinkers. Especially, measurement of serum GGT among type-2 diabetics may be helpful to predict the future risk of CHD.
Cardiovascular risk factors and γ-glutamyltransferase fractions in healthy individuals
Clinical Chemistry and Laboratory Medicine, 2000
Background: Serum g-glutamyltransferase activity (GGT), even when within its normal reference range, catalyzes low density lipoprotein oxidation in vitro and predicts cardiovascular events. Of the four GGT fractions (b-GGT, m-GGT, s-GGT, and f-GGT) recently identified in blood, only b-GGT is found within atherosclerotic plaques. Our goal was to identify the determinants of the GGT fractions (b-, m-, s-, and f-GGT) and their association with established cardiovascular risk factors in healthy subjects. Methods: Multiple linear regression analysis was applied to estimate the association of fractional GGT with gender, age, body mass index, arterial pressure (AP), plasma glucose, alanine aminotransferase (ALT), high and low density lipoproteins (LDL-C) cholesterol (HDL-C), triglycerides (TG) and C-reactive protein (CRP) in 200 healthy subjects. Results: All GGT fractions were associated with ALT; b-GGT with AP, TG, and CRP; m-GGT with LDL-C, TG and CRP; s-GGT with TG and CRP, and f-GGT only with LDL-C, whereas gender was associated with s-GGT and f-GGT only. Conclusions: In healthy individuals, cardiovascular risk factors are associated with high molecular weight GGT fractions, namely with b-GGT, the only form present within the plaque. This finding adds to the present knowledge concerning the relevance of GGT, within its reference range, for atherosclerosis-related events.
2008
Objective-The purpose of this study was to investigate the association of longitudinal change in serum ␥-glutamyltransferase (GGT) with mortality from cardiovascular disease (CVD). Methods and Results-A population-based cohort of 76 113 Austrian men and women with 455 331 serial GGT measurements was prospectively followed-up for a median of 10.2 years after assessment of longitudinal GGT change during an average period of 6.9 years. Cox proportional hazards regression with time-varying covariates was used to evaluate GGT change as an independent predictor for CVD death. Independently of baseline GGT and other classical CVD risk factors, a pronounced increase in GGT (7-year change Ͼ9.2 U/L) was significantly associated with increased total CVD mortality in men (Pϭ0.005); the adjusted hazard ratio (95% confidence interval) in comparison to stable GGT (7-year change Ϫ0.7 to 1.3 U/L) was 1.40 (1.09 to 1.81). Similarly, total CVD risk was elevated for increasing GGT in women, although effects were less pronounced and statistically significant only in subanalyses regarding coronary heart disease. Age of participants significantly modified the relation between GGT change and CVD mortality, with markedly stronger associations to be observable for younger individuals. Conclusion-Our study is the first to demonstrate that a longitudinal increase in GGT, independently of baseline GGT and even within its normal range, significantly increases risk of fatal CVD. (Arterioscler Thromb Vasc Biol.
European Journal of Cardiovascular Prevention & Rehabilitation, 2009
Background Although serum γ-glutamyltransferase (GGT) predicted cardiovascular diseases (CVD) in prospective studies and may be useful in risk assessment, prediction in older adults was weaker in several studies. Methods We performed a nested case-control study with 5-12-year follow-up in 137 CVD deaths and 249 controls (frequency-matched on age, sex, and examination year, age range 26-85 years). Results An age interaction of serum GGT and CVD mortality (P value for interaction= 0.02) was observed. After adjusting for ...
Clinical Chemistry
Background: ␥-Glutamyltransferase (GGT), which maintains cellular concentrations of glutathione, may be a marker of oxidative stress, and GGT itself may produce oxidative stress. We performed a prospective study to examine whether serum GGT predicts diabetes and hypertension. Methods: Study participants were 4844 black and white men and women 18-30 years of age in 1985-1986; they were reexamined 2, 5, 7, 10, and 15 years later. Year 0 GGT cutpoints were 12, 17, 25, and 36 U/L (overall 25th, 50th, 75th, and 90th percentiles; the laboratory cutpoints for abnormal are 40 U/L in women and 50 U/L in men). We deleted 32 participants with prevalent diabetes and 140 participants with prevalent hypertension from the respective incidence analyses. Results: After adjustment for study center, race, sex, and age in proportional hazards regression, the hazard ratios across year 0 GGT categories were 1.0, 1.6, 1.7, 4.0 (95% confidence interval, 2.0-8.1), and 5.5 (2.7-11.1) for 15year incident diabetes and 1.0, 1.2, 1.7 (1.2-2.2), 2.3 (1.7-3.2), and 2.3 (1.7-3.2) for hypertension. Additional adjustment for year 0 alcohol consumption, body mass index, cigarette smoking, and physical activity attenuated this relationship, but GGT remained a significant predictor. Conclusions: Serum GGT within a range regarded as physiologically normal is associated with incident diabetes and hypertension. Considering known functionality of GGT, these associations are consistent with a role for oxidative stress in risk for diabetes and hypertension.
Association of γ-glutamyl transferase with premature coronary artery disease
Biomedical Reports, 2016
Accumulating evidence from epidemiological studies suggests that higher γ-glutamyl transferase (GGT) levels in the blood are associated with the incident of cardiovascular disease (CVD), including atherosclerosis, and have prognostic importance. However, to the best of our knowledge, the association of the GGT level with premature coronary artery disease (CAD) in an Asian Indian population has not been evaluated. In the present study, 240 (120 unaffected and 120 CAD affected) young subjects (males, ≤45 years and females, ≤50 years) were selected. The markers assayed were GGT, high-sensitivity C-reactive protein, lipids, secretory phospholipase A2, neopterin, myeloperoxidase, interleukin-6, cystatin-C, tumor necrosis factor-like weak inducer of apoptosis and lipoprotein (a). The plasma GGT levels in these subjects showed a positive correlation with quantitative variables, such as waist circumference, triglycerides, neopterin levels and cross-sectional correlation with qualitative variable smoking. The findings suggest that the subjects in the highest tertile of GGT had a 2.1-fold [odds ratio (OR), 2.104; 95% confidence interval (CI), 1.063-4.165; P=0.033] higher risk of developing premature CAD in comparison with the reference tertile. Furthermore, a 1 U/l increase of GGT (on a log scale) increased the OR by 5.2-fold (OR, 5.208; 95% CI, 1.018-24.624; P=0.048) and 7.4-fold (OR, 7.492; 95% CI, 1.221-45.979; P= 0.030) on addition of associated risk factors. In conclusion, the elevated plasma GGT levels potentially indicate increased oxidative stress and the risk of developing premature CAD. Therefore, these findings could be potentially used in the risk stratification of premature CAD following further evaluation.
Background: ␥-Glutamyltransferase (GGT), which maintains cellular concentrations of glutathione, may be a marker of oxidative stress, and GGT itself may produce oxidative stress. We performed a prospective study to examine whether serum GGT predicts diabetes and hypertension. Methods: Study participants were 4844 black and white men and women 18 -30 years of age in 1985-1986; they were reexamined 2, 5, 7, 10, and 15 years later. Year 0 GGT cutpoints were 12, 17, 25, and 36 U/L (overall 25th, 50th, 75th, and 90th percentiles; the laboratory cutpoints for abnormal are 40 U/L in women and 50 U/L in men). We deleted 32 participants with prevalent diabetes and 140 participants with prevalent hypertension from the respective incidence analyses. Results: After adjustment for study center, race, sex, and age in proportional hazards regression, the hazard ratios across year 0 GGT categories were 1.0, 1.6, 1.7, 4.0 (95% confidence interval, 2.0 -8.1), and 5.5 (2.7-11.1) for 15year incident diabetes and 2) for hypertension. Additional adjustment for year 0 alcohol consumption, body mass index, cigarette smoking, and physical activity attenuated this relationship, but GGT remained a significant predictor. Conclusions: Serum GGT within a range regarded as physiologically normal is associated with incident diabetes and hypertension. Considering known functionality of GGT, these associations are consistent with a role for oxidative stress in risk for diabetes and hypertension. Nonstandard abbreviations: GGT, ␥-glutamyltransferase; CARDIA, Coronary Artery Risk Development in Young Adults; AST, aspartate aminotransferase; CRP, C-reactive protein; BMI, body mass index; RR, relative risk; and 95% CI, 95% confidence interval.
Additive prognostic value of gamma-glutamyltransferase in coronary artery disease
International Journal of Cardiology, 2009
Background: Serum gamma-glutamyl transferase activity (GGT) has been documented as an independent cardiovascular risk factor. However, to-date its value has not been compared with C-reactive protein (CRP) and other indexes in a multimarker prognostic strategy in 14 patients with coronary artery disease.
Longitudinal Change in Serum Gamma-Glutamyltransferase and Cardiovascular Disease Mortality
Arteriosclerosis, Thrombosis, and Vascular Biology, 2008
Objective— The purpose of this study was to investigate the association of longitudinal change in serum γ-glutamyltransferase (GGT) with mortality from cardiovascular disease (CVD). Methods and Results— A population-based cohort of 76 113 Austrian men and women with 455 331 serial GGT measurements was prospectively followed-up for a median of 10.2 years after assessment of longitudinal GGT change during an average period of 6.9 years. Cox proportional hazards regression with time-varying covariates was used to evaluate GGT change as an independent predictor for CVD death. Independently of baseline GGT and other classical CVD risk factors, a pronounced increase in GGT (7-year change >9.2 U/L) was significantly associated with increased total CVD mortality in men ( P =0.005); the adjusted hazard ratio (95% confidence interval) in comparison to stable GGT (7-year change −0.7 to 1.3 U/L) was 1.40 (1.09 to 1.81). Similarly, total CVD risk was elevated for increasing GGT in women, alth...