Baseline Gamma-glutamyl Transferase Levels Research Articles

Exposure to ambient air pollution and elevated blood levels of gamma-glutamyl transferase in a large Austrian cohort

Gamma glutamyl transferase (GGT) is related to oxidative stress and an indicator for liver damage. We investigated the association between air pollution and GGT in a large Austrian cohort (N = 116,109) to better understand how air pollution affects human health.Data come from voluntary prevention visits that were routinely collected within the Vorarlberg Health Monitoring and Prevention Program (VHM&PP). Recruitment was ongoing from 1985 to 2005. Blood was drawn and GGT measured centralized in two laboratories. Land use regression models were applied to estimate individuals' exposure at their home address for particulate matter (PM) with a diameter of <2.5 μm (PM2.5), <10 μm (PM10), fraction between 10 μm and 2.5 μm (PMcoarse), as well as PM2.5 absorbance (PM2.5abs), NO2, NOx and eight components of PM. Linear regression models, adjusting for relevant individual and community-level confounders were calculated.The study population was 56 % female with a mean age of 42 years and mean GGT was 19.0 units. Individual PM2.5 and NO2 exposures were essentially below European limit values of 25 and 40 μg/m3, respectively, with means of 13.58 μg/m3 for PM2.5 and 19.93 μg/m3 for NO2. Positive associations were observed for PM2.5, PM10, PM2.5abs, NO2, NOx, and Cu, K, S in PM2.5 and PM10 fractions and Zn mainly in PM2.5 fraction. The strongest association per interquartile range observed was an increase of serum GGT concentration by 1.40 % (95 %-CI: 0.85 %; 1.95 %) per 45.7 ng/m3 S in PM2.5. Associations were robust to adjustments for other biomarkers, in two-pollutant models and the subset with a stable residential history.We found that long-term exposure to air pollution (PM2.5, PM10, PM2.5abs, NO2, NOx) as well as certain elements, were positively associated with baseline GGT levels. The elements associated suggest a role of traffic emissions, long range transport and wood burning.

Association between serum gamma glutamyl transferase and fasting blood glucose in Chinese people: A 6-year follow-up study.

In this study, we aimed to investigate the relationships between gamma-glutamyl transferase (GGT) and fasting blood glucose (FBG) during a 6-year follow-up study of participants, and to determine whether GGT is a risk factor for FBG. A total of 1,369 individuals from the health examination survey in the urban area of Xuzhou, central China, were followed up for 6 years. The patients were divided into four groups based on their baseline GGT levels (in quartiles). The one-way analysis of variance (anova) method was used to compare the differences between the variables and baseline. The relationship between GGT and FBG levels was investigated using repeated measurements anova. The grouping of baseline GGT levels affected the changes in blood glucose during the 6-year follow-up study. In the GGT quartile subgroups, the annual mean increase in FBG levels showed a positive relationship with baseline GGT levels. This trend was even more aggregated in the highest baseline GGT group. Interactions among time course, baseline FBG and GGT groups in different participants together affected the change of FBG levels during the follow-up period. The repeated measures anova suggested that different baseline GGT groups were still significantly associated with increased FBG levels. GGT is a risk factor that affects FBG levels(P < 0.001). The annual mean increase in FBG levels showed a positive relationship with baseline GGT levels. Higher baseline GGT levels resulted in a faster annual mean increase in FBG. Thus, GGT can be used for the early detection of FBG-related disorders of glucose metabolism for clinical application.

Elevated gamma-glutamyl transpeptidase level is associated with an increased risk of hip fracture in postmenopausal women

The aim of this study was to evaluate the association between gamma-glutamyl transferase (GGT) levels and the risk of hip fracture among middle-aged women by using the Korean National Health Insurance Service claims database from 2002 to 2015. After exclusion of those with any chronic liver disease, heavy alcohol consumption, any missing values required for our analysis, or GGT levels less than 1 or greater than 99 percentile, we classified subjects into three groups according to baseline GGT levels. A total of 127,141 women aged 50 years or older were included for analysis (GGT range: 8–106 U/L). During an average 12.1 years of follow-up, 2758 patients sustained hip fractures (2.17%). Compared with the group in the lowest tertile, the group in the highest tertile had the highest cumulative incidence of hip fracture. One log-unit increase in GGT was associated with a 17% increased risk of hip fracture. Subgroup analysis by BMI (≥ 25 vs. < 25 kg/m2), presence of diabetes, levels of other liver enzymes, and alcohol consumption level did not show significant effect modification. In summary, elevated baseline GGT level was associated with an increased risk of hip fracture in postmenopausal women, independent of alcohol consumption and chronic liver disease.

Relationship Between Serum Gamma-Glutamyl Transferase Level and Impaired Fasting Glucose Among Chinese Community-Dwelling Adults: A Follow-Up Observation of 6 Years.

Objective: We aimed to investigate the relationship between serum gamma-glutamyl transferase (GGT) and fasting blood glucose (FBG) levels, as well as the cumulative risk of impaired fasting glucose (IFG) regulation in the Chinese adult population after 6 years of follow-up. Methods: A total of 1360 apparently healthy Chinese men and women who completed a community-based health examination survey and did not have IFG in central China in 2010 and 2016 were included in this study. The patients were divided into four groups according to their baseline GGT (in quartiles). The relationship between GGT levels and FBG levels was examined using general linear regression models. The effect of the GGT level on the risk of IFG was analyzed using multivariate logistic regression. The first quartile group of GGT levels was set as the dummy variable in the model, and the odds ratios and 95% confidence intervals of the remaining quartile groups relative to the first quartile group were obtained. Results: After 6 years of follow-up, 16.4% (188/1148) of participants were diagnosed with IFG. The cumulative incidence of IFG in the four groups according to their baseline GGT levels (in quartiles) was 7.7%, 16.1%, 15.8%, and 26.8%, respectively. Based on the Cox multiple regression, the hazard ratio for IFG increased by 28.9% for each unit of increase in the baseline GGT level after adjusting for the confounding factors. The GGT levels of participants in the first quartile were used as the reference group. The relative risks of IFG in the second, third, and fourth quartiles of GGT were 1.70, 1.55, and 2.46, respectively (P = 0.005). Conclusions: GGT was positively associated with the risk of IFG and can be used as an indicator to assess whether a patient may develop prediabetes.

Prognostic value of long-term gamma-glutamyl transferase variability in individuals with diabetes: a nationwide population-based study

We examined whether long-term gamma-glutamyl transferase (GGT) variability can predict cardiovascular disease (CVD) and mortality in individuals with diabetes. We included 698,937 Koreans diabetes patients older than 40 years without histories of CVD, chronic liver disease, or heavy alcoholics who received health exams supported by the Korean government more than once in 2009–2012 (baseline). We used Cox proportional analyses to estimate the risk of stroke, myocardial infarction (MI), and all-cause mortality until December 31, 2016, according to the quartiles of the average successive variability (ASV) of GGT measured during the five years before the baseline. A total 26,119, 15,103, and 39,982 cases of stroke, MI, and death, respectively, were found. GGT ASV quartile 4 had a significantly higher risk of stroke and all-cause mortality than quartile 1, with adjustment for risk factors, such as baseline glucose and GGT level, and comorbidities. Hazard ratios (95% confidence intervals) for GGT ASV quartile 4 were 1.06 (1.03–1.10) and 1.23 (1.20–1.27) for stroke and mortality, respectively. This significant association was shown consistently across the baseline GGT quartiles. GGT variability was related to the risk of stroke and all-cause mortality. The effect was most pronounced in all-cause mortality, irrespective of baseline GGT level.

Gamma-glutamyl transferase variability and risk of dementia: A nationwide study.

Variability in various biomarkers has emerged as a new clinical indicator for diseases including neurodegenerative disorders. Gamma-glutamyl transferase (GGT) has a potential to be involved in the pathogenesis of dementia due to its function as a marker of oxidative stress and atherosclerosis. We investigated the association between baseline GGT, GGT variability, and dementia risk for the first time in a large population. The Korean National Health Insurance Service datasets of claims and preventive health check-ups from 2004 to 2016 were used for this retrospective longitudinal study. The risk of incident dementia (all-cause dementia, Alzheimer's disease, and vascular dementia) was analyzed according to sex-specific quartiles of baseline GGT and GGT variability, and groups categorized by baseline GGT and GGT variability in ≥40-year-old individuals without baseline dementia (N = 6 046 442; mean follow-up 6.32 years). During follow-up, 166 851 cases of new dementia developed. The fully adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia increased in the higher quartiles of baseline GGT and GGT variability (HR [95% CI]: Q2, 1.034 [1.019-1.049]; Q3, 1.090 [1.075-1.105]; Q4, 1.212 [1.196-1.229]). The association between GGT variability quartiles and dementia risk remained significant even after adjusting for log-transformed baseline GGT level. The fully adjusted HRs for dementia was highest in the group with high baseline GGT concentration and the highest GGT variability quartile [HR (95% CI): 1.273 (1.250-1.296)]. Not only baseline GGT level, but also GGT variability may be an independent predictor of dementia, and might be used for risk stratification for future dementia.

Non-linear relationship between gamma-glutamyl transferase and type 2 diabetes mellitus risk: secondary analysis of a prospective cohort study.

ObjectiveTo investigate the association between gamma-glutamyl transferase (GGT) and type 2 diabetes mellitus (T2DM) risk.MethodsThis was a secondary analysis based on a publicly available DRYAD dataset that included 15 444 study participants that received medical examinations at a single centre in Japan between 2004 and 2015. Crude, minimally-adjusted and fully-adjusted regression models were used to evaluate the relationship between GGT levels and T2DM risk.ResultsThe study participants (mean ± SD age of 43.72 ± 8.90 years; 8415 of 15 444 [54.49%] were male) were followed-up for a median of 1968 days (5.39 years). After adjusting for potential covariates, a non-linear relationship between the baseline GGT level and T2DM incidence was observed. The inflection point for T2DM risk was 10 IU/l GGT; below this point, the T2DM incidence increased by 1.18-fold per unit change in GGT. Above this point, the association between GGT and the incidence rate of T2DM became nonsignificant.ConclusionBaseline GGT exhibited a non-linear association with T2DM incidence. Elevated GGT levels should be incorporated into routine screening for individuals at high risk of T2DM, allowing for early intervention targeting GGT to potentially reduce T2DM-related morbidity.

Gamma-glutamyl transferase and cardiovascular risk in nonalcoholic fatty liver disease: The Gut and Obesity Asia initiative.

BACKGROUNDGamma-glutamyl transferase (GGT) is associated with the risk of cardiovascular disease (CVD) in the general population.AIMTo identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).METHODSThis was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia (referred to as “GO ASIA”) workgroup. All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation (QRISK2-2017; developed by researchers at the United Kingdom National Health Service; https://qrisk.org/2017/; 10-year cardiovascular risk estimation) were included and compared to healthy controls with the same age, sex, and ethnicity. Relative risk was reported. QRISK2 score > 10% was defined as the high-CVD-risk group. Fibrosis stages 3 and 4 (F3 and F4) were considered advanced fibrosis.RESULTSA total of 1122 patients (73%) had complete data and were included in the final analysis; 314 (28%) had advanced fibrosis. The median age (interquartile range [IQR]) of the study population was 53 (44-60) years, 532 (47.4%) were females, and 492 (43.9%) were of Chinese ethnicity. The median 10-year CVD risk (IQR) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. The high-CVD-risk group was significantly older than the low-risk group (median [IQR]: 63 [59-67] vs 49 [41-55] years; P < 0.001). Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk (P < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: Median [IQR], high risk 60 [37-113] vs low risk 66 [38-103], P = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02).CONCLUSIONThe CVD risk of NAFLD patients is higher than that of healthy individuals. Baseline GGT level cannot predict CVD risk in NAFLD patients. However, advanced fibrosis is a predictor of a high CVD risk.

Liver Enzymes and the Risk of Atrial Fibrillation: A Meta-Analysis of Prospective Cohort Studies.

Background: The association between liver enzymes and the future development of atrial fibrillation (AF) from observational studies is unclear. We, therefore, performed a meta-analysis to systematically evaluate the relationship between liver enzymes and AF risk. Methods: We searched the PubMed and Embase databases for observational cohort studies assessing the association between liver enzymes and AF risk. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Results: Five prospective studies with 282,615 participants and 7062 AF events were included. The pooled fully adjusted RRs (95% CIs) for AF were 1.10 (1.06-1.14) per 1-standard deviation change in log baseline level of gamma glutamyltransferase (GGT). No positive association was found between alanine aminotransferase (ALT, RR 1.04, 95% CI 0.90-1.20, p = 0.607) or aspartate aminotransferase (AST, RR 1.05, 95% CI 0.96-1.15, p = 0.268) and the risk of AF. Conclusions: The baseline GGT level is positively associated with the AF risk in a log-linear manner. We found no significant association between ALT or AST and the risk of AF. However, further well-designed prospective studies are needed to confirm these findings and elucidate the pathophysiological mechanisms.

Associations of serum liver enzyme levels and their changes over time with all-cause and cause-specific mortality in the general population: a large-scale national health screening cohort study

ObjectivesTo investigate the associations of the levels of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT), at baseline and their changes over time with...

Gamma-glutamyl transferase predicts recurrences of atrial fibrillation after catheter ablation.

Catheter ablation is a popular therapy of atrial fibrillation (AF). Gamma-glutamyl transferase (GGT) is known as a marker of oxidative stress. The objective of this study was to ascertain the relationship between levels of GGT and recurrence of AF after catheter ablation. A total of 102 paroxysmal AF patients who underwent cryoballoon catheter ablation were enrolled. Serum samples were obtained to evaluate GGT levels before catheter ablation. Cox regression analysis was used to estimate the predictors of AF recurrence. Mean age of the cohort was 49.9 ± 11.7 and 63% of the patients were male. After a mean follow-up of 20 months, 19 (23%) patients had AF recurrences. The baseline GGT levels were significantly higher in patients who had AF recurrence [27 U/L (17-36) vs 18 U/L (13-22), P = 0.002]. The optimal cut-off value of GGT to predict AF recurrence was 23.5 U/L according to receiver operating characteristic curve analysis (area under the curve 0.72, P = 0.002). In the multivariable Cox regression analysis, baseline GGT > 23.5 was the only independent predictor of AF recurrence (hazard ratio (HR) 4.47, 95% confidence interval [1.66-12.09], P = 0.003). Our results indicate that elevated GGT is associated with AF recurrence. A simple measurement of GGT may help us to identify high-risk patients undergoing catheter ablation for AF.

Relation of antioxidant capacity of diet and markers of oxidative status with C-reactive protein and adipocytokines: a prospective study

BackgroundThe role of dietary antioxidants and plasma oxidant-antioxidant status in low-grade chronic inflammation and adipocytokine levels is not established yet. ObjectivesWe aimed to evaluate whether total dietary antioxidant capacity (assessed by dietary ferric reducing antioxidant potential (FRAP)), serum uric acid (UA) and gamma glutamyltransferase (GGT) were associated with low-grade chronic inflammation and circulating adipocytokines. MethodsData of 4506 participants aged ≥55years from the Rotterdam Study were analyzed. Baseline (1990–1993) FRAP score was assessed by a food frequency questionnaire. Baseline UA and GGT levels were assessed in non-fasting serum samples. Serum high sensitivity C-reactive protein (hs-CRP) was measured at baseline and 10years later. Plasma leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1) and resistin levels were assessed 10years later. ResultsA high FRAP score was associated with lower levels of UA and GGT. Overall, no association was found between FRAP and hs-CRP levels. FRAP score was associated with lower levels of leptin and PAI-1, higher levels of adiponectin, and no difference in resistin levels. Increased levels of UA were associated with higher levels of hs-CRP, PAI-1 and leptin; lower levels of adiponectin and no difference in resistin levels. Similarly, GGT was associated with higher levels of hs-CRP whereas no association was observed between GGT and adipocytokines. ConclusionThese findings suggest that overall antioxidant capacity of diet and low levels of UA are associated with circulating adipocytokines whereas no consistent association was found with hs-CRP.

Gamma-glutamyl transferase predicts recurrences of atrial fibrillation after catheter ablation

Background Catheter ablation is a popular therapy of atrial fibrillation (AF). Gamma-glutamyl transferase (GGT) is known as a marker of oxidative stress. The objective of this study was to ascertain the relationship between levels of GGT and recurrence of AF after catheter ablation.Methods A total of 102 paroxysmal AF patients who underwent cryoballoon catheter ablation were enrolled. Serum samples were obtained to evaluate GGT levels before catheter ablation. Cox regression analysis was used to estimate the predictors of AF recurrence.Results Mean age of the cohort was 49.9 ± 11.7 and 63% of the patients were male. After a mean follow-up of 20 months, 19 (23%) patients had AF recurrences. The baseline GGT levels were significantly higher in patients who had AF recurrence [27 U/L (17-36) vs 18 U/L (13-22), P= 0.002]. The optimal cut-off value of GGT to predict AF recurrence was 23.5 U/L according to receiver operating characteristic curve analysis (area under the curve 0.72, P= 0.002). In the multivariable Cox regression analysis, baseline GGT > 23.5 was the only independent predictor of AF recurrence (hazard ratio (HR) 4.47, 95% confidence interval [1.66-12.09], P= 0.003).Conclusions Our results indicate that elevated GGT is associated with AF recurrence. A simple measurement of GGT may help us to identify high-risk patients undergoing catheter ablation for AF.

Gamma glutamyltransferase and metabolic syndrome risk: a systematic review and dose-response meta-analysis.

We aimed to quantify and characterise in detail the nature of the dose-response relationship between baseline gamma glutamyltransferase (GGT) level and risk of incident metabolic syndrome (MetS) in the general population and determine the precise estimate of the magnitude of the association. We performed a systematic review and dose-response meta-analysis of published prospective cohort studies. Relevant studies were identified in a literature search of MEDLINE, EMBASE and Web of Science up to May 2014. A potential nonlinear relationship between GGT levels and MetS was examined using restricted cubic splines. Study-specific estimates were combined using random-effects models. Of the 323 studies reviewed, we included 10 prospective cohort studies with data on 67,905 participants comprising of 6595 incident MetS cases. In pooled analysis of seven studies with relevant data, baseline GGT level was statistically significantly positively associated with risk of MetS in a nonlinear fashion (p for nonlinearity = 0.003). Comparing individuals in the top vs. bottom thirds of baseline GGT levels, relative risk for MetS in pooled analysis of all 10 eligible studies was 1.88 (95% confidence interval: 1.49-2.38). Evidence was lacking of publication bias among the contributing studies. Baseline GGT level is positively and strongly associated with risk of the MetS in a nonlinear dose-response manner.

Liver enzymes and risk of all-cause mortality in general populations: a systematic review and meta-analysis

Gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), commonly used as markers of liver dysfunction, have been implicated with risk of all-cause mortality. The prospective evidence on the associations in general populations has not been reliably quantified. We conducted a systematic review and meta-analysis of published prospective cohort studies evaluating the associations of baseline levels of these enzymes with all-cause mortality in general populations. Relevant studies were identified in a literature search of MEDLINE, EMBASE and Web of Science up to March 2013. Authors of unpublished studies provided data on request. Nineteen unique cohort studies with aggregate data on over 9.24 million participants and 242 953 all-cause mortality outcomes were included. In a comparison of extreme thirds of baseline GGT and ALP levels, relative risks (RRs) (95% confidence intervals) for all-cause mortality were 1.60 (1.42-1.80) and 1.38 (1.17-1.63), respectively. The corresponding RRs for ALT were 0.82 (0.78-0.86) and 1.43 (1.08-1.90) in North American and Asian populations, respectively. There was no strong evidence of an association of AST with all-cause mortality: RR 1.23 (0.80-1.88). The pooled RRs per 5 U/l increment in GGT and ALP levels were 1.07 (1.04-1.10) and 1.03 (1.01-1.06), respectively. Available data indicate positive independent associations of baseline levels of GGT and ALP with all-cause mortality, consistent with linear dose-response relationships. There were geographical variations in the association of ALT with all-cause mortality which require further investigation. The potential incremental prognostic values of GGT and ALP in mortality risk assessment need evaluation.

A higher serum gamma-glutamyl transferase level could be associated with an increased risk of incident osteoporotic fractures in Korean men aged 50 years or older

Oxidative stress has detrimental effects on bone metabolism, and gamma-glutamyl transferase (GGT) is known to play an important role in the generation of free radical species through the extra-cellular hydrolysis of glutathione, the main cellular antioxidant. We performed a large longitudinal study with an average follow-up period of 3 years to investigate the association between baseline serum GGT levels and the development of future osteoporotic fractures (OFs) in men. A total of 16,036 Korean men aged 50 years or older who had undergone comprehensive routine health examinations were enrolled. Incident fractures at osteoporosis-related sites (e.g., hip, spine, distal radius, and proximal humerus) that occurred after baseline examinations were identified from the nationwide claims database of the Health Insurance Review and Assessment Service of Korea using selected ICD-10 codes. Among the study subjects, 156 cases (1.0%) developed incident OFs during the study period. The event rate was 32.7 (95% CI = 28.0-38.3) per 10,000 person-years. Multivariable adjusted Cox proportional hazard analyses adjusted for age, body mass index, lifestyle factors, and medical and drug histories revealed that the hazard ratio per standard deviation increase of the baseline GGT levels for the development of incident fractures was 1.115 (95% CI = 1.011-1.230). These data provide the first epidemiological evidence, in support of previous in vitro and animal studies, of the harmful effects of GGT on bone metabolism, and indicate that the serum GGT level may be a useful biomarker of poor bone health outcomes in men.

Population pharmacokinetics of posaconazole in neutropenic patients receiving chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome

Objective:The relationship between patient characteristics and posaconazole exposures was evaluated in a population pharmacokinetic (PK) model using trial data from neutropenic patients administered oral posaconazole suspension as antifungal prophylaxis.Methods:Data were analyzed using nonlinear mixed-effects modeling. Covariates were tested using the forward addition, Objective Function (OF) cut-off of 3.84, followed by the backward elimination (OF cut-off 10.88) steps in NONMEM. These covariates included demographics, mucositis, neutropenia, vomiting, diarrhea, proton pump inhibitor (PPI) or H2-receptor antagonist usage and baseline bilirubin or baseline gamma-glutamyl transferase (GGT) levels ≥2 × upper limit of normal (ULN). A correlation between posaconazole PK and the occurrence of invasive fungal infection (IFI) was also examined.Results:Statistically significant associations were demonstrated between posaconazole PK and diarrhea, PPI intake, race, and baseline GGT and bilirubin levels. These covariates did not predominate in patients who developed IFI.Conclusion:This analysis provides information regarding the correlation of patient covariates with posaconazole exposures estimated in a clinical setting. The results of this analysis agree with previously reported analyses. However, because of the successful prophylaxis and the low number of posaconazole-treated patients with IFI proven or probable (IFIPP), the absence of a statistically significant relationship between IFIPP and exposure may not mean this relationship does not exist. A meta-analysis of several efficacy trials or exploring alternate composite endpoints for efficacy may be needed to answer this question.

Early Virologic Failure in HIV-Coinfected Hepatitis C Patients Treated With the Peginterferon-Ribavirin Combination

Early Virologic Failure in HIV-Coinfected Hepatitis C Patients Treated With the Peginterferon-Ribavirin Combination

Gamma-glutamyltransferase: an effect modifier in the association between age and hypertension in a 4-year follow-up study.

We performed a prospective study to assess whether the relationship of age with hypertension was stronger in men with high normal serum gamma glutamyltransferase (GGT) than in those with lower GGT levels. The study population included 8170 healthy male workers in a steel manufacturing company who had undergone health examinations in both 1994 and 1998. The higher the baseline GGT level, the effect of age on the development of hypertension was stronger. The incidence of hypertension among those aged 25-34, 35-44 and 45-50 years was 0.9, 2.2, 3.8% in those with GGT<20 U/l; 1.0, 4.1, 12.5% in those with GGT between 20 and 39 U/l; and 1.9, 6.3, 17.2% in those with GGT> or =40 U/l, respectively. All relationships persisted after adjusting for baseline values of body mass index, alcohol intake, smoking, exercise, family history of hypertension, systolic and diastolic blood pressure, and changes of body mass index during 4 years (P for interaction=0.03). Our data supported the hypothesis that the effect of age on the development of hypertension differed by baseline GGT level, although the underlying mechanism for this interaction is unclear.