Alanine aminotransferase predicts coronary heart disease events: A 10-year follow-up of the Hoorn Study☆
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.
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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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2022, American Journal of the Medical SciencesCitation Excerpt :Elevations in ALT have been associated with increased incidence of endothelial dysfunction, metabolic syndrome and diabetes. In the Hoorn study, elevated levels of baseline ALT were associated with an increased incidence of CHD events even after adjusting for traditional cardiovascular risk factors like hypertension, diabetes and obesity over a 10 year follow up period.58 ALT elevation is related to fat accumulation in the liver and could represent systemic fat accumulation in multiple organs including the myocardium.
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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.