The relationship of gamma-glutamyltransferase to C-reactive protein and arterial stiffness

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Abstract

Background and aims

The relationships between γ-glutamyltransferase (GGT), C-reactive protein (CRP), and arterial stiffness have not been fully investigated. The aim of this study was to clarify whether serum GGT is related to CRP and arterial stiffness estimated using brachial-ankle pulse wave velocity (baPWV).

Methods and results

The subjects were 3412 males and 854 females. GGT, CRP, baPWV, and conventional risk factors were evaluated. On multiple regression analysis, after adjustment for the conventional risk factors, log GGT was significantly associated with log CRP in male and female subjects (male subjects: beta = 0.168, p < 0.0001; female subjects: beta = 0.098, p < 0.05). After adjustment for the conventional risk factors, log GGT was significantly associated with PWV in male subjects (beta = 0.060, p < 0.0001), but in female subjects, no significant relationships were found after adjustment (beta = 0.007, p = 0.82).

Conclusion

These results suggest that GGT is independently associated with an increased level of CRP in both males and females. In addition, in males, GGT is related to an increased level of arterial stiffness.

Introduction

Abnormal elevation of serum γ-glutamyltransferase (GGT) is used as a marker of alcohol consumption or liver disease [1]. Furthermore, several studies have indicated that slightly elevated serum GGT that is almost within the reference range is significantly associated with all-cause mortality [2], [3], as well as increased risks of myocardial infarction [4], [5] and stroke [6], [7]. These associations can be partly explained by the known correlation of GGT with cardiovascular risk factors, such as obesity [8], [9], dyslipidemia [10], [11], hypertension [12], [13], type 2 diabetes [13], [14], and metabolic syndrome [14].

Atherosclerosis is generally accepted to be an inflammatory disorder of the arterial wall [15]; the C-reactive protein (CRP) level is a strong predictor of cardiovascular events [16], [17], [18]. The CRP level is also correlated with many cardiovascular risk factors [19], [20], [21], [22]. There have been several reports that there is a relationship between serum GGT and CRP levels [13], [23], [24], [25], but the relationship has not been fully investigated, particularly in the Asian population.

Pulse wave velocity (PWV) is a valid maker of arterial stiffness [25], [26], and there have been many reports dealing with PWV and the development of atherosclerotic diseases [27], [28], [29], [30], [31]. However, the specific role of serum GGT in relation to early atherosclerosis remains unclear, and the relationship between GGT and arterial stiffness has not been fully investigated.

In this study, we investigated the associations of serum GGT, serum CRP, which is a cardiovascular risk factor, and arterial stiffness, which is as a marker of early-stage atherosclerosis.

Section snippets

Subjects

The subjects were local government employees (8229 men and 2194 women) aged 35 years or older who had their annual health checkup during the period from April 2003 through March 2004. We used a self-administered questionnaire to inquire about clinical history, family history, smoking, alcohol consumption, educational status, frequency of exercise, menopausal status, and hormone-replacement therapy. The questionnaires were distributed to the subjects in advance of their annual health checkup and

Results

The characteristics of the male and female subjects are presented in Table 1. The mean ages were 48.3 (SD 6.8) years for males and 46.8 (SD 7.2) years for females. The median CRP values were 0.044 (interquartile range: 0.023–0.089) mg/dL for males and 0.025 (interquartile range: 0.012–0.052) mg/dL for females. The median GGT values were 44 (interquartile range: 29–73) U/L for males and 21 (interquartile range: 16–31) U/L for females. The mean PWV values were 1638 (SD 199) cm/sec for males and

Discussion

One previous prospective study found a significant association between serum GGT and CRP levels [13] in the United States. Though the prospective study was valuable, the analysis was adjusted only for race, gender, and age. Two cross-sectional studies (one in the United States [23] and the other Italy [24]) have reported a significant association between serum GGT and CRP levels after adjustment for age, smoking, alcohol consumption, and BMI. Yamada et al. reported that there was a significant

Acknowledgments

This work was supported in part by a Grant-in-Aid for Young Scientists from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a Grant-in-Aid for Scientific Research from the Ministry of Health, Labour and Welfare of Japan.

We thank Mr. Manabu Shojiguchi, Mr. Hiroyuki Arizuka, Ms. Toyoko Enomoto, Mr. Takanori Mogi, Mr. Naoto Sasaki, Mr. Takeshi Tsuda, Ms. Tomoko Arihara, Dr. Toshiyuki Hayashi, Ms. Chizuko Sato, and Dr. Takehito Nakabayashi for their excellent

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