Elsevier

Atherosclerosis

Volume 191, Issue 2, April 2007, Pages 391-396
Atherosclerosis

Alanine aminotransferase predicts coronary heart disease events: A 10-year follow-up of the Hoorn Study

https://doi.org/10.1016/j.atherosclerosis.2006.04.006Get rights and content

Abstract

Alanine aminotransferase (ALT) is a marker of non-alcoholic fatty liver disease (NAFLD) and predicts incident type 2 diabetes mellitus (DM2). Recently, ALT was shown to be also associated with endothelial dysfunction and carotid atherosclerosis. We studied the predictive value of ALT for all-cause mortality, incident cardiovascular disease (CVD) and coronary heart disease (CHD) events in a population-based cohort of Caucasian men and women aged 50–75 years, at baseline. The 10-year risk of all-cause mortality, fatal and non-fatal CVD and CHD events in relation to ALT was assessed in 1439 subjects participating in the Hoorn Study, using Cox survival analysis. Subjects with prevalent CVD/CHD and missing data were excluded. As compared with the first tertile, the age- and sex-adjusted hazard ratios (95% confidence intervals) for all-cause mortality, CVD events and CHD events were 1.30 (0.92–1.83), 1.40 (1.09–1.81) and 2.04 (1.35–3.10), respectively, for subjects in the upper tertile of ALT. After adjustment for components of the metabolic syndrome and traditional risk factors, the association of ALT and CHD events remained significant for subjects in the third relative to those in the first tertile, with a hazard ratio of 1.88 (1.21–2.92) and 1.75 (1.12–2.73), respectively. In conclusion, the predictive value of ALT for coronary events, seems independent of traditional risk factors and the features of the metabolic syndrome in a population-based cohort. Further studies should confirm these findings and elucidate the pathophysiological mechanisms.

Introduction

Recently, the role of non-alcoholic fatty liver disease (NAFLD) in the pathogenesis of type 2 diabetes mellitus (DM2) has gained much interest. Several studies have demonstrated that NAFLD is associated with the components of the metabolic syndrome (MetS) and DM2 [1], [2], and fatty liver is considered to be the hepatic component of the MetS [3], [4]. Circulating concentrations of the liver transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been used as markers of NAFLD. Of these two liver enzymes, ALT appears to be the best marker of liver fat accumulation and is positively correlated with liver fat measured by magnetic resonance (MR) proton spectroscopy [5]. In cross-sectional and prospective studies ALT is associated with DM2 [6], [7]. Collectively, these data suggest that hepatic steatosis might play a role in the pathogenesis of DM2, most probably by contributing to the development of hepatic insulin resistance resulting, among others, in increased hepatic gluconeogenesis and overproduction of triglyceride-rich lipoproteins. Subjects with features of the MetS are not only at increased risk of DM2, but also at risk of developing cardiovascular (CVD) and coronary heart disease (CHD) [8].

In view of these observations, and the recently described associations between both NALFD or its marker ALT and vascular structural and functional properties [9], [10], we studied the predictive value of ALT for all-cause mortality, CVD and CHD events in a population-based study of diabetes and related complications in Caucasian men and women aged 50–75 years, at baseline.

Section snippets

Study population

Subjects were participants in the Hoorn Study, a prospective population-based cohort study of glucose metabolism and diabetes complications. The study population and research design have been described in detail previously [11]. In short, in 1989, a random sample of all men and women aged 50–75 was taken from the municipal registry of the medium-sized town of Hoorn in The Netherlands. Of the 3552 individuals, who where invited to take part in the study, 2540 agreed to participate (71.5%).

Baseline characteristics of the participants

The mean age of the 1439 participants (651 men and 788 women) was 60.9 (7.2) years. Table 1 shows the baseline characteristics of the participants divided into ALT tertiles. Subjects in the highest ALT tertile had a higher BMI, as well as waist and hip circumference. Also, they had higher fasting and 2 h post-load plasma glucose levels, fasting insulin levels, total cholesterol concentrations, and higher blood pressure. LDL-cholesterol tended to be different across the tertiles, whereas HbA1c

Discussion

The main novel finding of this population-based study with well-documented characterisation and follow-up of the participants, was a significant prospective association of ALT with CHD events, independent of the traditional CVD risk factors, such as systolic blood pressure, HbA1c, LDL-cholesterol and BMI, and independent of the components of the NCEP-defined metabolic syndrome. In addition we confirmed the cross-sectional association of ALT, a marker of NAFLD, with components of the MetS,

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    Part of the results have been presented in an oral presentation at 41st Scientific Meeting of the European Associations for the Study of Diabetes (EASD); 15 September 2005; Athens, Greece.

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