Association between serum gamma-glutamyltransferase and C-reactive protein
Introduction
Recently, in an attempt to improve global cardiovascular risk prediction, considerable interest has focused on C-reactive protein (CRP), a marker of inflammation that has been shown in multiple prospective epidemiological studies to predict incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death [1], [2].
On the other hand, serum gamma glutamyltransferase (GGT) levels within normal range was strongly associated with most cardiovascular disease risk factors and predicted the development of heart disease, hypertension, stroke, and type 2 diabetes [3], [4], [5], [6], [7], [8], [9]. In particular, serum GGT level has shown a strong graded relationship with incident diabetes, suggesting a role in the pathogenesis of diabetes [4], [5]. Although serum GGT activity has been commonly used as a marker for excessive alcohol consumption or liver diseases [10], neither alcohol consumption nor liver dysfunction likely explained these associations [4], [5]. A series of Coronary Artery Risk Development in Young Adults (CARDIA) studies [5], [11], [12] suggested that oxidative stress might explain these associations because serum GGT within normal range had dose-response relations with serum and/or dietary antioxidant vitamins and markers of oxidative stress such as F2-isoprostanes. Although the relationship between cellular GGT and serum GGT is not known, cellular GGT has been known to play an important role in antioxidant defense systems [13], [14], [15], [16]; paradoxically, cellular GGT may also be involved in the generation of reactive oxygen species in the presence of transition metals [17], [18], [19], [20], [21].
Oxidative stress appears to be a key component of many reactions associated with chronic inflammation [22], [23], [24]. Multiple oxidative processes play a critical role in inflammation and act on various intra- and extracellular pathways through specific mediators in conjunction with free radicals that amplify inflammatory reactions at specific sites [22], [23], [24]. In this context, the CARDIA finding of serum GGT predicting future concentrations of CRP in a dose-response manner could be of substantial interest. To our knowledge, however, the CARDIA finding [5] is the only report examining the association of serum GGT with CRP concentration. Therefore, we investigated the association between serum GGT and CRP concentration among another group of subjects, namely a representative sample of the US population using the third National Health and Nutrition Examination Survey (NHANES III).
Section snippets
Materials and methods
A detailed description of NHANES III can be found elsewhere [25]. Briefly, NHANES III, conducted from 1988 to 1994, was a national probability sample designed to provide national estimates of the health and nutritional status of the US civilian, noninstitutionalized population aged 2 months and older. Of the 18,825 NHANES III participants aged 20 years and older, we excluded 6518 with missing serum GGT or CRP and 288 who were pregnant, leaving 12,110 individuals available for analysis.
The
Results
The average age of the sample was 48.8 years. The proportions of ethnic groups were 44.0% for non-Hispanic white, 27.9% for non-Hispanic black, 23.5% for Mexican–American, and 4.6% for others. There were more females (52.8%) than males (47.2%) in the sample.
Serum GGT, mostly within normal range, was positively associated with serum CRP in a dose-response manner whatever criteria of serum CRP was used; geometric means, ≥3.0 mg/L, or ≥10.0 mg/L (Table 1). For example, adjusted relative risks of
Discussion
In this sample of the US population, we documented that serum GGT concentrations within its normal range are strongly and positively associated with serum CRP levels. This positive association was consistently demonstrated in all subgroups we examined. However, serum ALT, an enzyme more specific to the liver, was not positively associated with serum CRP. It is not possible to discern causal direction of association from this cross-sectional study. However, in the CARDIA study [5], serum GGT
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