Aspartate Aminotransferase to Alanine Aminotransferase Ratio and Arterial Stiffness in Persian Cohort Study

Document Type : Original Article

Authors

1 Persian Cohort Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Postdoc Researcher, Department of Medical Informatics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Introduction
Liver function tests such as AST/ALT ratio may play an important role in the progression of nonalcoholic fatty liver disease (NAFLD) and its related cardiovascular dysfunctions. The study aims to assess whether AST/ALT was associated with arterial stiffness in a large population-based cohort of apparently healthy Persian women and men.
Material and Methods: 
To evaluate arterial stiffness non-invasively, Pulse Wave Velocity (PWV) and Augmentation Index (AI) were measured in 5031 healthy adults. Laboratory parameters, including AST and ALT, were measured after all subject's blood samples were collected. The one-way-ANOVA, the Kruskal-Wallis, and chi-square tests were used to compare the AST/ALT ratio among groups with baseline characteristics of participants following the calculation of AST: ALT through the division of AST levels by ALT levels. The univariate linear regression model was used to assess the association between mean pulse wave velocity (PWV) and AST/ALT ratio quartiles. 
Results: 
The results showed no statically significant difference in Age, HR, and MET among the different AST/ALT groups. Univariate analysis displayed that age, SBP, DBP, FBS, TG, MET, Fatty liver status, and hypertension status were positively correlated with Mean PWV. Evaluation of univariate linear regression models presented that AST/ALT has a significant correlation with Mean PWV (β = -0.139, 95% confidence interval (CI): -0.032 to -0.021, P-value < 0.001). We found that there was no linear relationship.
Conclusions: 
According to the present study results, there was a significant negative correlation between AST/ALT with PWV. Moreover, a non-linear relationship between AST/ALT and PWV was observed as well.

Keywords

Main Subjects


  1. Tang B, Luo F, Zhao J, Ma J, Tan I, Butlin M, et al. Relationship between body mass index and arterial stiffness in a health assessment Chinese population. Medicine. 2020;99(3).
  2. Desamericq G, Tissot C-M, Akakpo S, Tropeano A-I, Millasseau S, Macquin-Mavier I. Carotid–femoral pulse wave velocity is not increased in obesity. American journal of hypertension. 2015;28(4):546-51.
  3. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics—2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56-e528.
  4. Sarrafzadegan N, Mohammmadifard N. Cardiovascular disease in Iran in the last 40 years: prevalence, mortality, morbidity, challenges and strategies for cardiovascular prevention. Archives of Iranian medicine. 2019; 22(4):204-10.
  5. Sobhani S, Aryan R, AkbariRad M, Ebrahimi Miandehi E, Alinezhad-Namaghi M, Sobhani SR, et al. The Association between Anthropometry Indices and Serum Concentrations of Gamma-Glutamyl Transferase, Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase. BioMed Research International. 2021;2021.
  6. Weng SF, Kai J, Guha IN, Qureshi N. The value of aspartate aminotransferase and alanine aminotransferase in cardiovascular disease risk assessment. Open heart. 2015;2(1):e000272.
  7. Adams LA, Harmsen S, Sauver JLS, Charatcharoenwitthaya P, Enders FB, Therneau T, et al. Nonalcoholic fatty liver disease increases risk of death among patients with diabetes: a community-based cohort study. The American journal of gastroenterology. 2010;105(7):1567.
  8. Söderberg C, Stål P, Askling J, Glaumann H, Lindberg G, Marmur J, et al. Decreased survival of subjects with elevated liver function tests during a 28‐year follow‐up. Hepatology. 2010; 51(2): 595-602.
  9. Giannini E, Risso D, Botta F, Chiarbonello B, Fasoli A, Malfatti F, et al. Validity and clinical utility of the aspartate aminotransferase–alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus–related chronic liver disease. Archives of internal medicine. 2003;163(2):218-24.
  10. Nyblom H, Berggren U, Balldin J, Olsson R. High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol and alcoholism. 2004; 39(4): 336-9.
  11. McPherson S, Stewart SF, Henderson E, Burt AD, Day CP. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010;59(9):1265-9.
  12. Angulo P, Bugianesi E, Bjornsson ES, Charatcharoenwitthaya P, Mills PR, Barrera F, et al. Simple noninvasive systems predict long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2013;145(4):
    782-9. e4.
  13. Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology. 2013;57(4):1357-65.
  14. Townsend N, Wickramasinghe K, Bhatnagar P, Smolina K, Nichols M, Leal J, et al. Coronary heart disease statistics 2012. 2012.
  15. Sobhani S, Vakili S, Javid Jam D, Aryan R, Khadem‐Rezaiyan M, Eslami S, et al. Relationship between anthropometric indices and arterial stiffness: Insights from an epidemiologic study. Obesity Science & Practice. 2018.
  16. Tohidinezhad F, Khorsand A, Zakavi SR, Rezvani R, Zarei-Ghanavati S, Abrishami M, et al. The burden and predisposing factors of non-communicable diseases in Mashhad University of Medical Sciences personnel: a prospective 15-year organizational cohort study protocol and baseline assessment. BMC Public Health. 2020; 20(1):1-15.
  17. Liu Y, Zhao P, Cheng M, Yu L, Cheng Z, Fan L, et al. AST to ALT ratio and arterial stiffness in non-fatty liver Japanese population: a secondary analysis based on a cross-sectional study. Lipids in health and disease. 2018;17(1):1-8.
  18. Mitchell GF, Hwang S-J, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, et al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation. 2010;121(4):505-11.
  19. Said MA, Eppinga RN, Lipsic E, Verweij N, van der Harst P. Relationship of arterial stiffness index and pulse pressure with cardiovascular disease and mortality. Journal of the American Heart Association. 2018;7(2):e007621.
  20. Glasser SP, Halberg DL, Sands C, Gamboa CM, Muntner P, Safford M. Is pulse pressure an independent risk factor for incident acute coronary heart disease events? The REGARDS study. American journal of hypertension. 2014;27(4):555-63.
  21. Shokawa T, Imazu M, Yamamoto H, Toyofuku M, Tasaki N, Okimoto T, et al. Pulse wave velocity predicts cardiovascular mortality findings from the Hawaii-Los Angeles-Hiroshima study. Circulation Journal. 2005;69(3):259-64.
  22. Zheng Y, Li Z, Shu H, Liu M, Chen Z, Huang J. Relationship between sum of the four limbs’ pulse pressure and brachial-ankle pulse wave velocity and atherosclerosis risk factors in Chinese adults. BioMed Research International. 2015;2015.
  23. Bonarjee VV. Arterial stiffness: a prognostic marker in coronary heart disease. available methods and clinical application. Frontiers in Cardiovascular Medicine. 2018;5:64.
  24. Gao F, Chen C, Lu J, Zheng J, Ma X-C, Yuan X-Y, et al. De Ritis ratio (AST/ALT) as an independent predictor of poor outcome in patients with acute ischemic stroke. Neuropsychiatric disease and treatment. 2017;13:1551.
  25. Ewid M, Sherif H, Allihimy AS, Alharbi SA, Aldrewesh DA, Alkuraydis SA, et al. AST/ALT ratio predicts the functional severity of chronic heart failure with reduced left ventricular ejection fraction. BMC Research Notes. 2020;13(1):1-6.
  26. Long MT, Pedley A, Massaro JM, Hoffmann U, Fox CS. The association between non-invasive hepatic fibrosis markers and cardiometabolic risk factors in the Framingham Heart Study. PloS one. 2016;11(6):e0157517.
  27. Rief P, Pichler M, Raggam R, Hafner F, Gerger A, Eller P, et al. The AST/ALT (De-Ritis) ratio: a novel marker for critical limb ischemia in peripheral arterial occlusive disease patients. Medicine. 2016;95(24).
  28. Wang J, Li J, Ren Y, Shi H, Rong X, Zhang X, et al. Association between alanine aminotransferase/aspartate aminotransferase ratio (AST/ALT Ratio) and coronary artery injury in children with Kawasaki disease. Cardiology research and practice. 2020;2020.
  29. Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Medical Clinics. 2014; 98(1):1-16.
  30. Park S, Lakatta EG. Role of inflammation in the pathogenesis of arterial stiffness. Yonsei medical journal. 2012;53(2):258-61.
  31. Yadav D, Choi E, Ahn SV, Baik SK, Cho YZ, Koh SB, et al. Incremental predictive value of serum AST-to-ALT ratio for incident metabolic syndrome: the ARIRANG Study. PLoS One. 2016;11(8):e0161304.