AST to ALT Ratio and Peripheral Arterial Disease in a Hypertensive Population—Is There a Link?

Abstract

In this issue of Angiology, Liu et al examine the association between the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and the prevalence of peripheral arterial disease (PAD) in participants of the Chinese Hypertension Registry Study (n 1⁄4 10 900 patients with hypertension, mean age 63.86+ 9.25 years, 47.06% male). Using the ankle– brachial index as an indicator of the presence of arterial insufficiency, the authors identified 350 patients with PAD (prevalence: 3.21%). The authors observed that the AST/ALT ratio was positively and independently associated with the risk of PAD (odds ratio [OR]: 1.31, 95% CI: 1.13-1.59), noting a significant increased risk of PAD for those in T3 versus T1 (OR: 1.49, 95% CI: 1.09-2.04, P 1⁄4 .005); by combining T1 and T2 (as a single reference group), the risk of PAD was positively associated with higher AST/ALT ratio, yielding a risk ratio of 1.52 (95% CI: 1.20-1.95). They concluded that an AST/ALT ratio �1.65 is associated with PAD risk and that it could help identify patients at high risk of vascular events. The authors considered several explanations for their findings: the increased risk of developing PAD in patients with an elevated AST/ALT ratio could lie in the coexistence of nonalcoholic fatty liver disease (NAFLD), with its propensity to exacerbate dyslipidemia; patients with an elevated AST/ALT ratio may exhibit insulin resistance (IR), which has been strongly linked with vascular risk and PAD. However, they suggest that such associations are insufficient to explain the observed interrelation, and other mechanisms linking PAD and AST/ALT merit consideration. Cardiovascular (CV) risk factors (RFs) are associated with an increased risk for the development of arterial disease in all vascular beds but differ in their individual impacts for each vascular bed. Peripheral arterial disease may coexist with coronary artery disease (CAD), carotid artery disease, and abdominal aortic aneurysms. The AST/ALT ratio, as an indicator of liver disease severity, is associated with an increased risk of CV disease (CVD). It can also be used as a simple independent predictor of left ventricular functional status in patients with heart failure and reduced ejection fraction. After adjusting for confounding RFs, a high AST/ALT ratio was an independent predictor of future CV mortality (hazard ratio [HR]: 2.51, 95% CI: 1.494.24, P < .0006). Rief and colleagues evaluated the correlation between the AST/ALT ratio and critical limb ischemia (CLI) in patients with occlusive PAD. In their cross-sectional study (1782 individuals with occlusive PAD), CLI was more frequent in patients with an AST/ALT ratio >1.67 versus those with an AST/ALT ratio <1.67 (41.9% vs 23.8%, P < .001). After adjusting for other well-established vascular RFs, an AST/ALT ratio >1.67 was associated with an OR of 2.0 (95% CI: 1.7-2.3) for CLI. Others observed that in patients without fatty liver disease there is no correlation between the AST/ALT ratio and brachial–ankle pulse wave velocity (a measure of arterial stiffness) in both crude (95% CI: �1.1 to 9.2, P 1⁄4 .122) and fully adjusted (95% CI: �2.0 to 6.4, P 1⁄4 .311) models. Moreover, the AST/ALT ratio has been reported to confer no additional predictive power over conventional CV RFs in the general population, although it may be useful in certain subgroups (eg, those with elevated ALT, type 2 diabetes mellitus (DM), features of metabolic syndrome [MetS], and alcohol usage). As the authors note, it seems that IR is an important, if not the primary, link between the AST/ALT radio and vascular disease. In this context, in a cohort (n 1⁄4 1063) of patients with IR and angiographically proven CAD, in whom vascular events were recorded over a 10-year period, the ALT/AST ratio was