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The value of aspartate aminotransferase and alanine aminotransferase in cardiovascular disease risk assessment.

ABSTRACT: OBJECTIVE:Aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio, reflecting liver disease severity, has been associated with increased risk of cardiovascular disease (CVD). The aim of this study was to evaluate whether the AST/ALT ratio improves established risk prediction tools in a primary care population. METHODS:Data were analysed from a prospective cohort of 29?316 UK primary care patients, aged 25-84?years with no history of CVD at baseline. Cox proportional hazards regression was used to derive 10-year multivariate risk models for the first occurrence of CVD based on two established risk prediction tools (Framingham and QRISK2), with and without including the AST/ALT ratio. Overall, model performance was assessed by discriminatory accuracy (AUC c-statistic). RESULTS:During a total follow-up of 120?462 person-years, 782 patients (59% men) experienced their first CVD event. Multivariate models showed that elevated AST/ALT ratios were significantly associated with CVD in men (Framingham: HR 1.37, 95% CI 1.05 to 1.79; QRISK2: HR 1.40, 95% CI 1.04 to 1.89) but not in women (Framingham: HR 1.06, 95% CI 0.78 to 1.43; QRISK2: HR 0.97, 95% CI 0.70 to 1.35). Including the AST/ALT ratio with all Framingham risk factors (AUC c-statistic: 0.72, 95% CI 0.71 to 0.74) or QRISK2 risk factors (AUC c-statistic: 0.73, 95% CI 0.71 to 0.74) resulted in no change in discrimination from the established risk prediction tools. Limiting analysis to those individuals with raised ALT showed that discrimination could improve by 5% and 4% with Framingham and QRISK2 risk factors, respectively. CONCLUSIONS:Elevated AST/ALT ratio is significantly associated with increased risk of developing CVD in men but not women. However, the ratio does not confer any additional benefits over established CVD risk prediction tools in the general population, but may have clinical utility in certain subgroups.

SUBMITTER: Weng SF

PROVIDER: S-EPMC4548065 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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The value of aspartate aminotransferase and alanine aminotransferase in cardiovascular disease risk assessment.

Weng Stephen F SF Kai Joe J Guha Indra Neil IN Qureshi Nadeem N

Open heart 20150821 1

<h4>Objective</h4>Aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio, reflecting liver disease severity, has been associated with increased risk of cardiovascular disease (CVD). The aim of this study was to evaluate whether the AST/ALT ratio improves established risk prediction tools in a primary care population.<h4>Methods</h4>Data were analysed from a prospective cohort of 29 316 UK primary care patients, aged 25-84 years with no history of CVD at baseline. Cox proportional ...[more]

PMID: 26322236

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Project description:The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.

Project description:ObjectiveRecent evidence has revealed that the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) may be closely associated with metabolic syndrome and insulin resistance. However, it is unclear whether the AST/ALT ratio correlates with prediabetes risk. The aim of our study was to examine the association between AST/ALT ratios and the risk of prediabetes among a large cohort of Chinese subjects.MethodsThis retrospective cohort study recruited 75204 Chinese adults with normoglycemia at baseline who underwent physical examinations at the Rich Healthcare Group from 2010 to 2016. The AST/ALT ratio at baseline was the target independent variable, and the risk of developing prediabetes during follow-up was the dependent variable. Cox proportional-hazards regression was used to evaluate the independent association between the AST/ALT ratio and prediabetes. This study identified nonlinear relationships by applying a generalized additive model (GAM) and smooth curve fitting. In order to assess the robustness of this study, we performed a series of sensitivity analyses. Moreover, we performed a subgroup analysis to evaluate the consistency of the association in different subgroups. Data from this study have been updated on the DATADRYAD website.ResultsThe AST/ALT ratio was negatively and independently related to the prediabetes risk among Chinese adults (HR: 0.76, 95% CI: 0.75-0.84, P<0.0001) after adjusting demographic and biochemical covariates. Furthermore, a nonlinear relationship between the AST/ALT ratio and the risk of developing prediabetes was found at an inflection point of 1.50 for the AST/ALT ratio. When the AST/ALT ratio was to the left of the inflection point (AST/ALT ratio ≤ 1.50), the AST/ALT ratio was negatively related to the prediabetes risk (HR:0.70, 95%CI: 0.65-0.76, P<0.0001). In contrast, the relationship tended to be saturated when the AST/ALT ratio was more than 1.50 (HR: 1.01, 95%CI: 0.89-1.15, P=0.8976). Our findings remained robust across a range of sensitivity analyses. Subgroup analysis revealed that other variables did not alter the relationship between the AST/ALT ratio and prediabetes risk.ConclusionThis study revealed that AST/ALT ratio was negatively and independently associated with prediabetes risk among Chinese participants. The relationship between the AST/ALT ratio and prediabetes risk was nonlinear, and AST/ALT ratio ≤ 1.50 was strongly inversely correlated with prediabetes risk.

Project description:BackgroundAccumulating evidence has revealed that the aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio is a promising novel biomarker for insulin resistance (IR) and metabolic diseases. However, research on the association between the AST/ALT ratio and the incidence of diabetes progressing from prediabetes remains lacking. Herein, this study aimed to evaluate the relationship between the baseline AST/ALT ratio and risks of diabetes in patients with prediabetes.MethodsThis was a retrospective cohort study involving a total of 82,683 participants across 32 regions and 11 cities in China from 2010 to 2016. Data was obtained based on the DATADRYAD database from the health check screening program. Participants were stratified according to the interquartile range of the AST/ALT ratio (groups Q1 to Q4). The Cox proportional hazard model and smooth curve fitting were used to explore the relationship between the baseline AST/ALT ratio and the risk of diabetes in prediabetic patients. In addition, subgroup analysis was used to further validate the stability of the results.ResultsThe mean age of the selected participants was 49.9 ± 14.0 years, with 66.8% of them being male. During the follow-up period 1,273 participants (11.3%) developed diabetes progressing from prediabetes during the follow-up period. Participants who developed diabetes were older and were more likely to be male. The fully-adjusted Cox proportional hazard model revealed that the AST/ALT ratio was negatively associated with the risk of diabetes in prediabetic patients (HR = 0.40, 95% CI: 0.33 to 0.48, P < 0.001). Higher AST/ALT ratio groups (Q4) also presented with a lower risk of progressing into diabetes (HR = 0.35, 95% CI: 0.29 to 0.43, P < 0.001, respectively) compared with the lowest quintile group (Q1). Through subgroup analysis and interaction tests, it was found that the association stably existed in all subgroup variables, and there were a stronger interactive effects in people with age < 45 years, and TG ≤ 1.7 mmol/L in the association between AST/ALT ratio and diabetes incidences in patients with prediabetes (P for interaction < 0.05).ConclusionAccording to our study, a higher AST/ALT ratio is associated with a lower risk of progressing into diabetes from prediabetes. Regular monitoring of AST/ALT ratio dynamics and corresponding interventions can help prevent or slow prediabetes progression for diabetes.

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The value of aspartate aminotransferase and alanine aminotransferase in cardiovascular disease risk assessment.

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The value of aspartate aminotransferase and alanine aminotransferase in cardiovascular disease risk assessment.

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