Relationship between non-alcoholic fatty liver disease and cardiovascular disease: focus on the use of ursodeoxycholic acid

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, affecting about 25% of the general population and up to 70–90% of obese or diabetic patients. Due to the increasing frequency of cardiometabolic polymorbidity phenotype and the fact that, on the one hand, NAFLD patients often have concomitant cardiovascular pathology and, on the other hand, that patients with cardiovascular disease (CVD) are often diagnosed with concomitant NAFLD, the relationship of NAFLD with CVD is currently subject to active study. Common metabolic risk factors and pathogenetic mechanisms such as systemic inflammation, endothelial dysfunction, lipid and glucose metabolism disorders, and insulin resistance are considered as the main determinants of the relationship between NAFLD and CVD. The involvement of the latter in the development of these diseases suggests that NAFLD and CVD are comorbid conditions, aggravating the course of each other, and, accordingly, the adjustment of lifestyle, risk factors and treatment of NAFLD can reduce the risks of CVD. In this regard, the purpose of this review is to analyze the relationship between NAFLD and CVD, as well as to discuss therapeutic strategies, in particular, the prospects of ursodeoxycholic acid in patients with NAFLD and CVD.

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Olga A. Polyakova

Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: docpolyakova.olga@gmail.com
ORCID iD: 0000-0003-0491-8823
SPIN-code: 5104-9117

Cand. Sci. (Med.), Assistant of the Department of Therapy and Polymorbid Pathology n.a. Academician M.S. Vovsi

Russian Federation, Moscow

Yu. M. Tkachenko

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: docpolyakova.olga@gmail.com
ORCID iD: 0009-0006-5867-4173
Russian Federation, Moscow

O. D. Ostroumova

Russian Medical Academy of Continuous Professional Education

Email: docpolyakova.olga@gmail.com
ORCID iD: 0000-0002-0795-8225
SPIN-code: 3910-6585
Russian Federation, Moscow

References

  1. Pouwels S., Sakran N, Graham Y., et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord. 2022;22(1):63. doi: 10.1186/s12902-022-00980-1.
  2. Oni E.T., Agatston A.S., Blaha M.J., et al. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis. 2013;230(2):258–67. doi: 10.1016/j.atherosclerosis.2013.07.052.
  3. Burra P., Becchetti C., Germani G. NAFLD and liver transplantation: Disease burden, current management and future challenges. JHEP Rep. 2020;2(6):100192. doi: 10.1016/j.jhepr.2020.100192.
  4. Allen A.M., Therneau T.M., Larson J.J., et al. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year-community study. Hepatology. 2018;67(5):1726–36. doi: 10.1002/hep.29546.
  5. Zhang X., Wu M., Liu Z., et al. Increasing prevalence of NAFLD/NASH among children, adolescents and young adults from 1990 to 2017: a population-based observational study. BMJ Open. 2021;11(5):e042843. doi: 10.1136/bmjopen-2020-042843.
  6. Неалкогольная жировая болезнь печени у взрослых. Клинические реклмендации, утвержденные Минздравом России (2022). [Non-alcoholic fatty liver disease in adults. Clinical recommendations approved by the Ministry of Health of Russia (2022). (In Russ.)]. URL: https://cr.minzdrav.gov.ru/recomend/748_1
  7. Pan J.J., Fallon M.B. Gender and racial differences in nonalcoholic fatty liver disease. World J Hepatol. 2014;6(5):274–83. doi: 10.4254/wjh.v6.i5.274.
  8. Yang J.D., Abdelmalek M.F., Pang H., et al. Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis. Hepatology. 2014;59(4):1406–14. doi: 10.1002/hep.26761.
  9. Sarkar M.A., Suzuki A., Abdelmalek M.F., et al. Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD. Clin Gastroenterol Hepatol. 2021;19(6):1267–74.e1. doi: 10.1016/j.cgh.2020.09.045.
  10. Khalid Y.S., Dasu N.R., Suga H., et al. Increased cardiovascular events and mortality in females with NAFLD: a meta-analysis. Am J Cardiovasc Dis. 2020;10(3):258–71.
  11. Armstrong M.J., Adams L.A., Canbay A., Syn W.K. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology. 2014;59(3):1174–97. doi: 10.1002/hep.26717/.
  12. Söderberg C., Stal .P, Askling J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology. 2010;51(2):595–602. doi: 10.1002/hep.23314.
  13. Ekstedt M., Hagstrom H., Nasr P., et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547–54. doi: 10.1002/hep.27368.
  14. Targher G., Byrne C.D/, Lonardo A/, et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol. 2016;65(3):589–600. doi: 10.1016/j.jhep.2016.05.013.
  15. Jaruvongvanich V., Wirunsawanya K., Sanguankeo A., Upala S. Nonalcoholic fatty liver disease is associated with coronary artery calcification: A systematic review and meta-analysis. Dig Liver Dis. 2016;48(12):1410–17. doi: 10.1016/j.dld.2016.09.002.
  16. Adams L.A., Anstee Q.M., Tilg H., Targher G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut. 2017;66(6):1138–53. doi: 10.1136/gutjnl-2017-313884.
  17. Полякова О.А., Остроумова О.Д., Ковалева Г.П., Павлеева Е.Е. Коморбидность неалкогольной жировой болезни печени и сердечно-сосудистых заболеваний: фокус на адеметионин и урсодезоксихолевую кислоту. Медицинский алфавит. 2021;1(29):13–20. [Polyakova O.A., Ostroumova O.D., Kovaleva G.P., Pavleeva E.E. Comorbidity of non-alcoholic fatty liver disease and cardiovascular disease: focus on ademetionine and ursodeoxycholic acid. Meditsinskii alfavit. 2021;1(29):13–20. (In Russ.)]. doi: 10.33667/2078-5631-2021-29-13-20.
  18. Ipsen D.H., Lykkesfeldt J., Tveden-Nyborg P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci. 2018;75(18):3313–27. doi: 10.1007/s00018-018-2860-6.
  19. Lechner K., McKenzie A.L., Krankel N., et al. High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation. Metab Syndr Relat Disord. 2020;18(4):176–85. doi: 10.1089/met.2019.0115.
  20. Libby P., Everett B.M. Novel Antiatherosclerotic Therapies. Arterioscler Thromb Vasc Biol. 2019;39(4):538–45. doi: 10.1161/ATVBAHA.118.310958.
  21. Al-Mrabeh A., Zhyzhneuskaya S.V., Peters C., et al. Hepatic Lipoprotein Export and Remission of Human Type 2 Diabetes after Weight Loss. Cell Metab. 2020;31(2):233–49.e4. doi: 10.1016/j.cmet.2019.11.018.
  22. Lai H.T.M., de Oliveira Otto M.C., Lee Y., et al. Serial Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway and Total Mortality, Cause-Specific Mortality, and Cardiovascular Diseases in the Cardiovascular Health Study. J Am Heart Assoc. 2019;8(22):e012881. doi: 10.1161/JAHA.119.012881.
  23. Ogresta D., Mrzljak A., Cigrovski Berkovic M., et al. Coagulation and Endothelial Dysfunction Associated with NAFLD: Current Status and Therapeutic Implications. J Clin Transl Hepatol. 2022;10(2):339–55. doi: 10.14218/JCTH.2021.00268.
  24. Costa D.S., Guahnon M.P., Seganfredo F.B., et al. Vitamin B12 and homocysteine levels in patients with NAFLD: a systematic review and metanalysis. Arq Gastroenterol. 2021;58(2):234–39. doi: 10.1590/S0004-2803.202100000-42.
  25. Pacana T., Cazanave S., Verdianelli A., et al. Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation in Diet-Induced Nonalcoholic Fatty Liver Disease. PLoS One. 2015;10(8):e0136822. doi: 10.1371/journal.pone.0136822.
  26. Stahl E.P., Dhindsa D.S., Lee S.K., et al. Nonalcoholic Fatty Liver Disease and the Heart: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(8):948–63. doi: 10.1016/j.jacc.2018.11.050.
  27. Francque S.M., van der Graaff D., Kwanten W.J. Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications. J Hepatol. 2016;65(2):425–43. doi: 10.1016/j.jhep.2016.04.005.
  28. Chen Z., Qin H., Qiu S., et al. Correlation of triglyceride to high-density lipoprotein cholesterol ratio with nonalcoholic fatty liver disease among the non-obese Chinese population with normal blood lipid levels: a retrospective cohort research. Lipids Health Dis. 2019;18(1):162. doi: 10.1186/s12944-019-1104-6.
  29. Deprince A., Haas J.T., Staels B. Dysregulated lipid metabolism links NAFLD to cardiovascular disease. Mol Metab. 2020;42:101092. doi: 10.1016/j.molmet.2020.101092.
  30. Miranda P.J., DeFronzo R.A., Califf R.M., Guyton J.R. Metabolic syndrome: definition, pathophysiology, and mechanisms. Am Heart J. 2005;149(1):33–45. doi: 10.1016/j.ahj.2004.07.013.
  31. Taskinen M.R. Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia. 2003;46(6):733–49. doi: 10.1007/s00125-003-1111-y.
  32. Ruscica M., Ferri N., Macchi C., et al. Liver fat accumulation is associated with circulating PCSK9. Ann Med. 2016;48(5):384–91. doi: 10.1080/07853890.2016.1188328.
  33. Lebeau P.F., Byun J.H., Platko K., et al. Diet-induced hepatic steatosis abrogates cell-surface LDLR by inducing de novo PCSK9 expression in mice. J Biol Chem. 2019;294(23):9037–47. doi: 10.1074/jbc.RA119.008094.
  34. Zewinger S., Reiser J., Jankowski V., et al. Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation. Nat Immunol. 2020;21(1):30–41. doi: 10.1038/s41590-019-0548-1.
  35. Shulman G.I. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014;371(12):1131–41. doi: 10.1056/NEJMra1011035.
  36. Petersen M.C., Shulman G.I. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018;98(4):2133–23. doi: 10.1152/physrev.00063.2017.
  37. Worm N. Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD. Nutrients. 2020;12(5):1316. doi: 10.3390/nu12051316.
  38. Lopez-Suarez A., Guerrero J.M., Elvira-Gonzalez J., et al. Nonalcoholic fatty liver disease is associated with blood pressure in hypertensive and nonhypertensive individuals from the general population with normal levels of alanine aminotransferase. Eur J Gastroenterol Hepatol. 2011;23(11):1011–17. doi: 10.1097/MEG.0b013e32834b8d52.
  39. Lorbeer R., Bayerl C., Auweter S., et al. Association between MRI-derived hepatic fat fraction and blood pressure in participants without history of cardiovascular disease. J Hypertens. 2017;35(4):737–44. doi: 10.1097/HJH.0000000000001245.
  40. Ciardullo S., Monti T., Sala I., et al. Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in US Adults Across Blood Pressure Categories. Hypertension. 2020;76(2):562–68. doi: 10.1161/HYPERTENSIONAHA.120.15220.
  41. Baharvand-Ahmadi B., Sharifi K., Namdari M. Prevalence of non-alcoholic fatty liver disease in patients with coronary artery disease. ARYA Atheroscler. 2016;12(4):201–5.
  42. Saraya S., Saraya M., Mahmoud M., et al. The associations between coronary artery disease, and non-alcoholic fatty liver disease by computed tomography. Egypt Heart J. 2021;73(1):96. doi: 10.1186/s43044-021-00222-0.
  43. Gholoobi A., Gifani M., Gholoobi A., et al. Relationship between the prevalence and severity of non-alcoholic fatty liver disease and coronary artery disease: Findings from a cross-sectional study of a referral center in northeast Iran. JGH Open. 2022;6(5):330–37. doi: 10.1002/jgh3.12746.
  44. Montemezzo M., AlTurki A., Stahlschmidt F., et al. Nonalcoholic Fatty Liver Disease and Coronary Artery Disease: Big Brothers in Patients with Acute Coronary Syndrome. Scientific World Journal. 2020;2020:8489238. doi: 10.1155/2020/8489238.
  45. Tsuchida T., Shiraishi M., Ohta T., et al. Ursodeoxycholic acid improves insulin sensitivity and hepatic steatosis by inducing the excretion of hepatic lipids in high-fat diet-fed KK-Ay mice. Metabolism. 2012;61(7):944–53. doi: 10.1016/j.metabol.2011.10.023.
  46. Sokolovic D., Nikolic J., Kocic G., et al. The effect of ursodeoxycholic acid on oxidative stress level and DNase activity in rat liver after bile duct ligation. Drug Chem Toxicol. 2013;36(2):141-148. doi: 10.3109/01480545.2012.658919.
  47. Xiang Z., Chen Y.P., Ma K.F, et al. The role of ursodeoxycholic acid in non-alcoholic steatohepatitis: a systematic review. BMC Gastroenterol. 2013;13:140. doi: 10.1186/1471-230X-13-140.
  48. Ozel Coskun B.D., Yucesoy M., Gursoy S., et al. Effects of ursodeoxycholic acid therapy on carotid intima media thickness, apolipoprotein A1, apolipoprotein B, and apolipoprotein B/A1 ratio in nonalcoholic steatohepatitis. Eur J Gastroenterol Hepatol. 2015;27(2):142–49. doi: 10.1097/MEG.0000000000000264.
  49. Nadinskaia M., Maevskaya M., Ivashkin V., et al. Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2021;27(10):959–75. doi: 10.3748/wjg.v27.i10.959.
  50. Martsevich S.Yu., Kutishenko N.P., Drozdova L.Yu., et al. Study of ursodeoxycholic acid influence on efficacy and safety of statin therapy in patients with diseases of the liver, gall bladder and/or biliary tract (the RAKURS study). Rational Pharmacotherapy in Cardiology. 2014;10(2):147–52. doi: 10.20996/1819-6446-2014-10-2-147-152.
  51. Cabezas Gelabert R. Efecto del acido ursodesoxicolico combinado con estatinas para el tratamiento de la hipercolesterolemia: ensayo clinico prospectivo. Rev Clin Esp. 2004;204(1):632–35.
  52. Zhang R., Ma W.Q., Fu M.J., et al. Overview of bile acid signaling in the cardiovascular system. World J Clin Cases. 2021;9(2):308–20. doi: 10.12998/wjcc.v9.i2.308.
  53. Кардиоваскулярная профилактика 2022. Российские национальные рекомендации. [Cardiovascular prevention 2022. Russian national recommendations. (In Russ.)]. URL: https://scardio.ru/content/Guidelines/Kardiovascular_profilaktika_2022.pdf

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