Aminotransferases are associated with insulin resistance and atherosclerosis in rheumatoid arthritis

Patrick H Dessein,Angela J Woodiwiss,Gavin R Norton,Barry I Joffe

doi:10.1186/1471-2261-7-31

Abstract

BackgroundSerum aminotransferase concentrations are reportedly strongly associated with insulin resistance, an established cardiovascular risk factor that is not routinely assessed in clinical practice. We therefore explored the possibility that serum aminotransferase concentrations are as closely related to large artery disease as insulin resistance in rheumatoid arthritis (RA).MethodsCarotid artery plaque (ultrasonography), insulin resistance and liver enzymes (prior to methotrexate (MTX) were determined in 77 consecutive patients with RA (43 with and 34 without MTX).ResultsSerum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were associated with insulin resistance in univariate analysis (R = 0.54, p < 0.0001 and R = 0.36, p = 0.001, respectively) and after adjustment for age, gender and waist circumference (partial R = 0.43, p = 0.0001 and partial R = 0.37, p = 0.001, respectively). ALT and AST concentrations were higher in patients with plaque as compared to in those without plaque (ALT (u/l): 27 [22-32] versus 20 [18-23], p = 0.02; AST (u/l): 25 [21-28] versus 20 [19-22], p = 0.02). The odds ratios [95% CI] for plaque were 1.92 [1.14–3.24] (p = 0.01), 1.93 [1.17–3.16] (p = 0.009) and 1.82 [1.13–2.93] (p = 0.01) for 1 SD increase in ALT (~10 u/l) and AST (~6 u/l) concentrations and in logarithmically transformed homeostasis model assessment of insulin resistance (HOMA-IR) (~0.2 uU.mmol/ml.l), respectively. After adjustment for the potentially confounding characteristics of age, sex, hypertension and hypothyroidism in logistic regression models, ALT (p = 0.049) and AST concentrations (p = 0.027) remained associated with plaque whereas the HOMA-IR did not (p = 0.08). AST concentrations (p = 0.049) were associated with plaque independent of insulin resistance whereas the HOMA-IR (p = 0.1) was not associated with plaque independent of AST concentrations.ConclusionWithin currently recommended reference ranges, serum aminotransferase concentrations may be strongly associated with insulin resistance and atherosclerosis in patients with RA. The measurement of aminotransferase concentrations could be a useful tool in cardiovascular risk stratification in patients with RA.

Highlights

Serum aminotransferase concentrations are reportedly strongly associated with insulin resistance, an established cardiovascular risk factor that is not routinely assessed in clinical practice
Relationships between aminotransferase concentrations and carotid artery atherosclerosis ALT and AST concentrations were higher in patients with plaque as compared to in those without plaque (ALT (u/ l): 27 [22,23,24,25,26,27,28,29,30,31,32] vs 20 [18,19,20,21,22,23], p = 0.02; AST (u/l): 25 [2128] vs 20 [19,20,21,22], p = 0.02)
In this study we found, for the first time, that high serum aminotransferase concentrations were associated with the presence of carotid artery plaque independent of age, gender, hypertension and hypothyroidism, and of conventional cardiovascular risk factors as estimated by the Framingham score

Summary

Introduction

Serum aminotransferase concentrations are reportedly strongly associated with insulin resistance, an established cardiovascular risk factor that is not routinely assessed in clinical practice. We explored the possibility that serum aminotransferase concentrations are as closely related to large artery disease as insulin resistance in rheumatoid arthritis (RA). Insulin resistance further predicts cardiovascular disease independent of other metabolic syndrome features [3,4,5,6,7]. An independent association of insulin resistance with carotid as well as coronary artery atherosclerosis has been reported in RA [16,17]. We and others recently found that in contrast to the homeostasis model assessment of insulin resistance (HOMA-IR) [16,17], the NCEP:ATPIII defined metabolic syndrome was not associated with carotid and coronary artery atherosclerosis in a patients with RA. Outcomebased studies should be performed to assess the value of HOMA-IR in RA, or an alternative and more sensitive approach should be devised to predict the impact of metabolic syndrome features on cardiovascular risk in RA

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Discussion

Conclusion