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Gamma-glutamyltransferase: determinants and association with mortality from ischemic heart disease and all causes
G Wannamethee1, S Ebrahim, A G Shaper
1University Department of Public Health, Hospital School of Medicine, London, England.
Insights
Elevated gamma-glutamyltransferase (GGT) levels are linked to increased cardiovascular disease mortality, particularly ischemic heart disease, in middle-aged men. This association persists even after adjusting for various risk factors like BMI and diabetes.
Area of Science:
- Biochemistry
- Epidemiology
- Cardiology
Background:
- Serum gamma-glutamyltransferase (GGT) is an enzyme found in the liver and bile ducts.
- Elevated GGT levels have been associated with various health conditions, including cardiovascular disease (CVD).
Purpose of the Study:
- To investigate the association between serum GGT levels and cardiovascular disease risk factors.
- To examine the relationship between GGT levels and mortality from all causes, CVD, and non-cardiovascular diseases in middle-aged men.
Main Methods:
- Prospective study of 7,613 middle-aged British men followed for 11.5 years.
- Analysis of serum GGT levels and their correlation with risk factors, mortality, and clinical outcomes.
- Statistical adjustments for factors including alcohol intake, BMI, smoking, diabetes, and blood pressure.
Main Results:
- GGT levels were strongly associated with all-cause mortality, primarily due to ischemic heart disease and non-cancer deaths.
- Elevated GGT was linked to increased alcohol intake, BMI, smoking, diabetes, hypertension, dyslipidemia, and reduced lung function.
- After adjustments, the highest GGT quintile remained associated with increased all-cause (RR=1.22) and ischemic heart disease mortality (RR=1.42).
- Increased ischemic heart disease mortality risk was more pronounced in men with pre-existing ischemic heart disease, especially previous myocardial infarction.
- Increased non-cardiovascular disease mortality was observed in men without pre-existing ischemic heart disease, linked to hepatic cirrhosis.
Conclusions:
- Serum GGT levels are associated with numerous risk factors beyond alcohol, including BMI, diabetes, and cholesterol.
- Elevated GGT is an independent predictor of ischemic heart disease mortality, particularly in men with existing heart conditions.
- The biological significance of elevated GGT in men with pre-existing ischemic heart disease warrants further investigation.
Abstract:
The association of serum levels of gamma-glutamyltransferase (GGT) with cardiovascular disease risk factors, and with mortality from all causes, cardiovascular disease, and non-cardiovascular diseases, has been examined in a prospective study of 7,613 middle-aged British men followed for 11.5 years. GGT levels were strongly associated with all-cause mortality, largely due to a significant increase in deaths from ischemic heart disease and other non-cardiovascular disease causes, i.e., non-cancer deaths, in the top quintile of the GGT distribution. No association was seen with cancer mortality. However, GGT was significantly (positively) associated with alcohol intake, body mass index, smoking, preexisting ischemic heart disease, diabetes mellitus, antihypertensive medication, systolic and diastolic blood pressure, total and high density lipoprotein cholesterol, heart rate, and blood glucose, and negatively associated with physical activity and lung function (forced expiratory volume in 1 second (FEV1)). After adjustment for these personal characteristics and biologic variables, elevated GGT (highest quintile > or = 24 unit/liter vs. the rest) was still associated with a significant increase in mortality from all causes (relative risk (RR) = 1.22, 95% confidence interval (CI) 1.01-1.42; n = 818 deaths) and from ischemic heart disease (RR = 1.42, 95% CI 1.12-1.80; n = 332 deaths). The increase in other non-cardiovascular disease causes was of marginal significance (RR = 1.45, 95% CI 0.95-2.20; n = 127 deaths). When examined separately by the presence or absence of preexisting ischemic heart disease, the increased risk of ischemic heart disease mortality was more marked in those with evidence of ischemic heart disease at screening, particularly in those with previous myocardial infarction (RR = 1.67, 95% CI 1.03-2.69; n = 84 deaths). The increased risk of other non-cardiovascular disease deaths was only seen in men without preexisting ischemic heart disease, largely due to an excess of hepatic cirrhosis. In summary, many factors other than alcohol intake are associated with increased levels of GGT, in particular body mass index, diabetes mellitus, and serum total cholesterol. The finding of increased risk of ischemic heart disease mortality seen in men with preexisting ischemic heart disease is related to the severity of the underlying myocardial damage. The biologic significance of raised GGT in men with preexisting ischemic heart disease merits further study.