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BMC Cardiovascular Disorders

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Open Access 01-12-2021 | Research article

Serum alanine aminotransferase activity and risk factors for cardiovascular disease in a Caucasian population: the Tromsø study

Author: Svein Ivar Bekkelund

Published in: BMC Cardiovascular Disorders | Issue 1/2021

Abstract

Background

High and low levels of serum alanine aminotransferase (ALT) are both associated with cardiovascular diseases (CVD) risks especially in elderly, but the mechanisms are less known. This study investigated associations between ALT and CVD risk factors including effects of sex and age in a Caucasian population.

Methods

Cross-sectional data were analysed sex-stratified in 2555 men (mean age 60.4 years) and 2858 women (mean age 60.0 years) from the population study Tromsø 6. Associations were assessed by variance analysis and multivariable logistic regression of odds to have abnormal ALT. Risk factors included body mass index (BMI), waist-to-hip-ratio, blood pressure, lipids, glucose, glycated haemoglobin and high-sensitive C-reactive protein (CRP).

Results

Abnormal elevated ALT was detected in 113 men (4.4%) and 188 women (6.6%). Most CVD risk factors associated positively with ALT in both sexes except systolic blood pressure and CRP (women only), while ALT was positively associated with age in men when adjusted for CVD risk factors, P < 0.001. BMI predicted ALT in men (OR 0.94; 95% CI 0.88–1.00, P = 0.047) and women (OR 0.90; 95% CI 0.86–0.95, P < 0.001). A linear inversed association between age and ALT in men and a non-linear inversed U-trend in women with maximum level between 60 and 64 years were found.

Conclusion

This study confirms a positive relationship between ALT and CVD risk factors, particularly BMI. Age is not a major confounder in the ALT-CVD relationship, but separate sex-analyses is recommended in such studies.

Yokoyama M, Watanabe T, Otaki Y, Takahashi H, Arimoto T, Shishido T, et al. Association of the aspartate aminotransferase to alanine aminotransferase ratio with BNP level and cardiovascular mortality in the general population: The Yamagata study 10-year follow-up. Dis Markers. 2016;2016:4857917. https://doi.org/10.1155/2016/4857917.CrossRefPubMedPubMedCentral

Schindhelm RK, Dekker JM, Nijpels G, Bouter LM, Stehouwer CD, Heine RJ, et al. Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study. Atherosclerosis. 2007;191(2):391–6. https://doi.org/10.1016/j.atherosclerosis.2006.04.006.CrossRefPubMed

Klein M, Iazzettii L, Speiser P, Carey D, Shelov S, Accacha S, et al. Alanine transferase: an independent indicator of adiposity related comorbidity risk in youth. J Diabetes. 2015;7(5):649–56. https://doi.org/10.1111/1753-0407.12221.CrossRefPubMed

Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2003;124(1):71–9. https://doi.org/10.1053/gast.2003.50004.CrossRefPubMed

Hanley AJ, Wagenknecht LE, Festa A, D’Agostino RB Jr, Haffner SM. Alanine aminotransferase and directly measured insulin sensitivity in a multiethnic cohort: the Insulin Resistance Atherosclerosis Study. Diabetes Care. 2007;30(7):1819–27. https://doi.org/10.2337/dc07-0086.CrossRefPubMed

Vozarova B, Stefan N, Lindsay RS, Saremi A, Pratley RE, Bogardus C, et al. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes. 2002;51(6):1889–95.CrossRef

Ballestri S, Zona S, Targher G, Romagnoli D, Baldelli E, Nascimbeni F, et al. Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome: evidence from a systematic review and meta-analysis. J Gastroenterol Hepatol. 2016;31(5):936–44. https://doi.org/10.1111/jgh.13264.CrossRefPubMed

Chang Y, Ryu S, Sung E, Jang Y. Higher concentrations of alanine aminotransferase within the reference interval predict nonalcoholic fatty liver disease. Clin Chem. 2007;53(4):686–92. https://doi.org/10.1373/clinchem.2006.081257.CrossRefPubMed

Martin-Rodriguez JL, Gonzalez-Cantero J, Gonzalez-Cantero A, Arrebola JP, Gonzalez-Calvin JL. Diagnostic accuracy of serum alanine aminotransferase as biomarker for nonalcoholic fatty liver disease and insulin resistance in healthy subjects, using 3T MR spectroscopy. Medicine. 2017;96:17: e6770; doi:https://doi.org/10.1097/md.0000000000006770.

10.

Chen KW, Meng FC, Shih YL, Su FY, Lin YP, Lin F, et al. Sex-specific association between metabolic abnormalities and elevated alanine aminotransferase levels in a military cohort: the CHIEF study. Int J Environ Res Public Health. 2018;15:3. https://doi.org/10.3390/ijerph15030545.CrossRef

11.

Preuss HG, Kaats GR, Mrvichin N, Bagchi D, Preuss JM. Circulating ALT levels in healthy volunteers over life-span: assessing aging paradox and nutritional implications. J Am Coll Nutr. 2019;38(8):661–9. https://doi.org/10.1080/07315724.2019.1580169.CrossRefPubMed

12.

Deetman PE, Alkhalaf A, Landman GW, Groenier KH, Kootstra-Ros JE, Navis G, et al. Alanine aminotransferase and mortality in patients with type 2 diabetes (ZODIAC-38). Eur J Clin Invest. 2015;45(8):807–14. https://doi.org/10.1111/eci.12474.CrossRefPubMed

13.

Kunutsor SK, Bakker SJ, Kootstra-Ros JE, Blokzijl H, Gansevoort RT, Dullaart RP. Inverse linear associations between liver aminotransferases and incident cardiovascular disease risk: the PREVEND study. Atherosclerosis. 2015;243(1):138–47. https://doi.org/10.1016/j.atherosclerosis.2015.09.006.CrossRefPubMed

14.

Ruhl CE, Everhart JE. The association of low serum alanine aminotransferase activity with mortality in the US population. Am J Epidemiol. 2013;178(12):1702–11. https://doi.org/10.1093/aje/kwt209.CrossRefPubMedPubMedCentral

15.

Ndrepepa G, Holdenrieder S, Colleran R, Cassese S, Xhepa E, Fusaro M, et al. Inverse association of alanine aminotransferase within normal range with prognosis in patients with coronary artery disease. Clin Chim Acta. 2019;496:55–61. https://doi.org/10.1016/j.cca.2019.06.021.CrossRefPubMed

16.

Afarideh M, Aryan Z, Ghajar A, Noshad S, Nakhjavani M, Baber U, et al. Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes. Atherosclerosis. 2016;254:42–51. https://doi.org/10.1016/j.atherosclerosis.2016.09.009.CrossRefPubMed

17.

Dong MH, Bettencourt R, Barrett-Connor E, Loomba R. Alanine aminotransferase decreases with age: the Rancho Bernardo Study. PloS One. 2010;5:12:e14254; doi:https://doi.org/10.1371/journal.pone.0014254.

18.

Vespasiani-Gentilucci U, Gallo P, Piccinocchi G, Piccinocchi R, Schena E, Galati G, et al. Determinants of alanine aminotransferase levels in a large population from Southern Italy: relationship between alanine aminotransferase and age. Dig Liver Dis. 2014;46(10):909–15. https://doi.org/10.1016/j.dld.2014.05.021.CrossRefPubMed

19.

Elinav E, Ben-Dov IZ, Ackerman E, Kiderman A, Glikberg F, Shapira Y, et al. Correlation between serum alanine aminotransferase activity and age: an inverted U curve pattern. Am J Gastroenterol. 2005;100(10):2201–4. https://doi.org/10.1111/j.1572-0241.2005.41822.x.CrossRefPubMed

20.

Jacobsen BK, Eggen AE, Mathiesen EB, Wilsgaard T, Njolstad I. Cohort profile: the Tromso study. Int J Epidemiol. 2012;41(4):961–7. https://doi.org/10.1093/ije/dyr049.CrossRefPubMed

21.

Johnsen SH, Lilleng H, Wilsgaard T, Bekkelund SI. Creatine kinase activity and blood pressure in a normal population: the Tromso study. J Hypertens. 2011;29(1):36–42. https://doi.org/10.1097/HJH.0b013e32834068e0.CrossRefPubMed

22.

Bekkelund SI, Jorde R. Alanine aminotransferase and body composition in obese men and women. Dis Markers. 2019;2019:1695874. https://doi.org/10.1155/2019/1695874.CrossRefPubMedPubMedCentral

23.

Rustad P, Felding P, Franzson L, Kairisto V, Lahti A, Martensson A, et al. The Nordic Reference Interval Project 2000: recommended reference intervals for 25 common biochemical properties. Scand J Clin Lab Invest. 2004;64(4):271–84. https://doi.org/10.1080/00365510410006324.CrossRefPubMed

24.

Kunutsor SK, Apekey TA, Seddoh D, Walley J. Liver enzymes and risk of all-cause mortality in general populations: a systematic review and meta-analysis. Int J Epidemiol. 2014;43(1):187–201. https://doi.org/10.1093/ije/dyt192.CrossRefPubMed

25.

Liu Z, Ning H, Que S, Wang L, Qin X, Peng T. Complex association between alanine aminotransferase activity and mortality in general population: a systematic review and meta-analysis of prospective studies. PloS One. 2014;9:3:e91410; doi:https://doi.org/10.1371/journal.pone.0091410.

26.

Visaria A, Pai S, Fayngersh A, Kothari N. Association between alanine aminotransferase within the normal range and all-cause and cause-specific mortality: A nationwide cohort study. PloS One. 2020;15:11:e0242431; doi:https://doi.org/10.1371/journal.pone.0242431.

27.

Dong MH, Bettencourt R, Brenner DA, Barrett-Connor E, Loomba R. Serum levels of alanine aminotransferase decrease with age in longitudinal analysis. Clin Gastroenterol Hepatol. 2012;10(3):285-90.e1. https://doi.org/10.1016/j.cgh.2011.10.014.CrossRefPubMed

28.

Le Couteur DG, Blyth FM, Creasey HM, Handelsman DJ, Naganathan V, Sambrook PN, et al. The association of alanine transaminase with aging, frailty, and mortality. J Gerontol A Biol Sci Med Sci. 2010;65(7):712–7. https://doi.org/10.1093/gerona/glq082.CrossRefPubMed

29.

Myers J, Lata K, Chowdhury S, McAuley P, Jain N, Froelicher V. The obesity paradox and weight loss. Am J Med. 2011;124(10):924–30. https://doi.org/10.1016/j.amjmed.2011.04.018.CrossRefPubMed

30.

Bussler S, Vogel M, Pietzner D, Harms K, Buzek T, Penke M, et al. New pediatric percentiles of liver enzyme serum levels (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase): effects of age, sex, body mass index, and pubertal stage. Hepatology. 2017. https://doi.org/10.1002/hep.29542.CrossRef

31.

Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002;137(1):1–10.CrossRef

32.

Poustchi H, George J, Esmaili S, Esna-Ashari F, Ardalan G, Sepanlou SG, et al. Gender differences in healthy ranges for serum alanine aminotransferase levels in adolescence. PloS One. 2011;6:6:e21178; doi:https://doi.org/10.1371/journal.pone.0021178.

33.

Feitosa MF, Reiner AP, Wojczynski MK, Graff M, North KE, Carr JJ, et al. Sex-influenced association of nonalcoholic fatty liver disease with coronary heart disease. Atherosclerosis. 2013;227(2):420–4. https://doi.org/10.1016/j.atherosclerosis.2013.01.013.CrossRefPubMedPubMedCentral

Title: Serum alanine aminotransferase activity and risk factors for cardiovascular disease in a Caucasian population: the Tromsø study
Author: Svein Ivar Bekkelund
Publication date: 01-12-2021
Publisher: BioMed Central
Published in: BMC Cardiovascular Disorders / Issue 1/2021
Electronic ISSN: 1471-2261
DOI: https://doi.org/10.1186/s12872-020-01826-1

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Serum alanine aminotransferase activity and risk factors for cardiovascular disease in a Caucasian population: the Tromsø study

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Conclusion

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