nach oben

03.05.2024 | REVIEW

Metabolic dysfunction-associated steatotic liver disease and atherosclerosis

verfasst von: Yulino Castillo-Núñez, Paloma Almeda-Valdes, Guillermo González-Gálvez, María del Rosario Arechavaleta-Granell

Erschienen in: Current Diabetes Reports

Einloggen, um Zugang zu erhalten

Abstract

Purpose of review

To update information about the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis. This review emphasizes the potential mechanisms linking MASLD with atherosclerosis and the possible causal relationships between these conditions.

Recent findings

An increased risk of cardiovascular disease is related to MASLD. Several molecular, cellular, and metabolic mechanisms have been described to explain the development of atherothrombosis in MASLD patients. These include atherogenic dyslipidemia, low-grade vascular inflammation, endothelial dysfunction, foam cell formation, proliferation of vascular smooth muscle cells, insulin resistance, gut microbiota dysbiosis, activation of renin-angiotensin and sympathetic nervous systems, hypercoagulability, and decreased fibrinolysis. Also, there is recent evidence suggesting an association between genetically driven liver fat and coronary heart disease mediated by the causal effect of apoB-containing lipoproteins. Several meta-analyses and systematic reviews have reported a strong association between MASLD and cardiovascular outcomes.

Summary

MASLD is an important and independent risk factor for atherosclerosis development. Multiple mechanisms may be involved in this association. Further research is required to establish a causal association between MASLD and atherosclerosis.

Bril F, Cusi K. Nonalcoholic fatty liver disease: The new complication of type 2 diabetes mellitus. Endocrinol Metab Clin N Am. 2016;45:765–81.CrossRef

Bril F, Cusi K. Management of nonalcoholic fatty liver disease in patients with type 2 diabetes: A call to action. Diabetes Care. 2017;40:419–30.PubMedCrossRef

Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73:202–9.PubMedCrossRef

Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79:1542–56.PubMedCrossRef

Zheng KI, Sun DQ, Jin Y, Zhu PW, Zheng MH. Clinical utility of the MAFLD definition. J Hepatol. 2021;74:989–91.PubMedCrossRef

Hagström H, Vessby J, Ekstedt M, Shang Y. 99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical. J Hepatol. 2024;80(2):e76–7.PubMedCrossRef

Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142:1592–609.PubMedCrossRef

Balta S. Atherosclerosis and non-alcoholic fatty liver disease. Angiology. 2022;73:701–11.PubMedCrossRef

Niederseer D, Wernly B, Aigner E, Stickel F, Datz C. NAFLD and Cardiovascular Diseases: Epidemiological, Mechanistic and Therapeutic Considerations. J Clin Med. 2021;10(3):467.PubMedPubMedCentralCrossRef

10.

Brea A, Puzo J. Non-alcoholic fatty liver disease and cardiovascular risk. Int J Cardiol. 2013;167:1109–17.PubMedCrossRef

11.

Leey J, Cusi K. Editorial: diabetes, obesity and clinical inertia-the recipe for advanced NASH. Aliment Pharmacol Ther. 2018;47:1220–1.PubMedCrossRef

12.

Davis TME. Diabetes and metabolic dysfunction-associated fatty liver disease. Metabolism. 2021;123: 154868.PubMedCrossRef

13.

Wen W, Li H, Wang C, Chen C, Tang J, Zhou M, Hong X, Cheng Y, Wu Q, Zhang X, Feng Z, Wang M. Metabolic dysfunction-associated fatty liver disease and cardiovascular disease: a meta-analysis. Front Endocrinol (Lausanne). 2022;13: 934225.PubMedCrossRef

14.

Mantovani A, Csermely A, Tilg H, Byrne CD, Targher G. Comparative effects of non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease on risk of incidente cardiovascular events: a meta-analysis of about 13 million individuals. Gut. 2023;72:1433–6.PubMedCrossRef

15.

Schonmann Y, Yeshua H, Bentov I, Zelber-Sagi S. Liver fbrosis marker is an independent predictor of cardiovascular morbidity and mortality in the general population. Dig Liver Dis. 2021;53:79–85.PubMedCrossRef

16.

Baratta F, Pastori D, Angelico F, Balla A, Paganini AM, Cocomello N, Ferro D, Violi F, Sanyal AJ, Del Ben M. Nonalcoholic fatty liver disease and fibrosis associated with increased risk of cardiovascular events in a prospective study. Clin Gastroenterol Hepatol. 2020;18:2324-2331.e4.PubMedCrossRef

17.

Tamaki N, Kurosaki M, Takahashi Y, Itakura Y, Inada K, Kirino S, Yamashita K, Sekiguchi S, Hayakawa Y, Osawa L, Higuchi M, Takaura K, Maeyashiki C, Kaneko S, Yasui Y, Tsuchiya K, Nakanishi H, Itakura J, Izumi N. Liver fbrosis and fatty liver as independent risk factors for cardiovascular disease. J Gastroenterol Hepatol. 2021;36:2960–6.PubMedCrossRef

18.

Han E, Lee YH, Lee JS, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Lee BW, Kang ES, Cha BS, Kim SU. Fibrotic burden determines cardiovascular risk among subjects with metabolic dysfunction-associated fatty liver disease. Gut Liver. 2022;16:786–97.PubMedPubMedCentralCrossRef

19.

Duell PB, Welty FK, Miller M, Chait A, Hammond G, Ahmad Z, et al. Nonalcoholic fatty liver disease and cardiovascular risk: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2022;42:e168–85.PubMedCrossRef

20.

Kasper P, Martin A, Lang S, Kütting F, Goeser T, Demir M, Steffen HM. NAFLD and cardiovascular diseases: a clinical review. Clin Res Cardiol. 2021;110:921–93721.PubMedCrossRef

21.

•Zhang L, She ZG, Li H, Zhang XJ. Non-alcoholic fatty liver disease: a metabolic burden promoting atherosclerosis. Clin Sci (Lond). 2020;134:1775–99. This review summarizes the key molecular events and cellular factors contributing to the metabolic burden induced by NAFLD on atherosclerosis.PubMedCrossRef

22.

•Li M, Wang H, Zhang XJ, Cai J, Li H. NAFLD: an emerging causal factor for cardiovascular disease. Physiology (Bethesda). 2023;38(6):0. This review summarizes the evidence from prospective clinical and Mendelian randomization studies that underscore the potential causal relationship between NAFLD and cardiovascular disease.

23.

Bali AD, Rosenzveig A, Frishman WH, Aronow WS. Nonalcoholic fatty liver disease and cardiovascular disease: causation or association. Cardiol Rev. 2023;24:e000537.

24.

Bril F, Lomonaco R, Cusi K. The challenge of managing dyslipidemia in patients with nonalcoholic fatty liver disease. Clin Lipidol. 2012;7:471–81.CrossRef

25.

Martin A, Lang S, Goeser T, Demir M, Steffen HM, Kasper P. Management of dyslipidemia in patients with non-alcoholic fatty liver disease. Curr Atheroscler Rep. 2022;24:533–46.PubMedPubMedCentralCrossRef

26.

Behbodikhah J, Ahmed S, Elsayi A, Kasselman LJ, De Leon J, Glass AD, Reiss AB. Apolipoprotein B and cardiovascular disease: biomarker and potential therapeutic target. Metabolites. 2021;11:690.PubMedPubMedCentralCrossRef

27.

Cole J, Zubirán R, Wolska A, Jialal I, Remaley AT. Use of apolipoprotein B in the era of precision medicine: time for a paradigm change? J Clin Med. 2023;12:5737.PubMedPubMedCentralCrossRef

28.

Matikainen N, Taskinen MR, Stennabb S, Lundbom N, Hakkarainen A, Vaaralahti K, Raivio T. Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat. Eur J Endocrinol. 2012;166:487–92.PubMedCrossRef

29.

Mehta A, Shapiro MD. Apolipoproteins in vascular biology and atherosclerotic disease. Nat Rev Cardiol. 2022;19:168–79.PubMedCrossRef

30.

Hegele RA. Apolipoprotein C-III inhibition to lower triglycerides: one ring to rule them all? Eur Heart J. 2022;43:1413–5.PubMedCrossRef

31.

de la Parra Soto LG, Gutiérrez-Uribe JA, Sharma A, Ramírez-Jiménez AK. Is apo-CIII the new cardiovascular target? An analysis of its current clinical and dietetic therapies. Nutr Metab Cardiovasc Dis. 2022;32:295–308.PubMedCrossRef

32.

Deprince A, Hennuyer N, Kooijman S, Pronk ACM, Baugé E, Lienard V, et al. Apolipoprotein F is reduced in humans with steatosis and controls plasma triglyceride-rich lipoprotein metabolism. Hepatology. 2023;77:1287–302.PubMedCrossRef

33.

Hafiane A, Gianopoulos I, Sorci-Thomas MG, Daskalopoulou SS. Current models of apolipoproteina A-I lipidation by adenosine triphosphate binding cassette transporter A1. Curr Opin Lipidol. 2022;33:139–45.PubMedCrossRef

34.

Naito C, Hashimoto M, Watanabe K, Shirai R, Takahashi Y, Kojima M, Watanabe R, Sato K, Iso Y, Matsuyama TA, Suzuki H, Ishibashi-Ueda H, Watanabe T. Facilitatory effects of fetuin-A on atherosclerosis. Atherosclerosis. 2016;246:344–51.PubMedCrossRef

35.

Gupta RM, Libby P, Barton M. Linking regulation of nitric oxide to endothelin-1: the yin and yang of vascular tone in the atherosclerotic plaque. Atherosclerosis. 2020;292:201–3.PubMedCrossRef

36.

Rafnsson A, Matic LP, Lengquist M, Mahdi A, Shemyakin A, Paulsson-Berne G, Hansson GK, Gabrielsen A, Hedin U, Yang J, Pernow J. Endothelin-1 increases expression and activity of arginase 2 via ETB receptors and is co-expressed with arginase 2 in human atherosclerotic plaques. Atherosclerosis. 2020;292:215–23.PubMedCrossRef

37.

Loffredo L, Baratta F, Ludovica P, Battaglia S, Carnevale R, Nocella C, Novo M, Pannitteri G, Ceci F, Angelico F, Violi F, Del Ben M. Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis. Nutr Metab Cardiovasc Dis. 2018;28:143–9.CrossRef

38.

Jiang M, Zhao XM, Jiang ZS, Wang GX, Zhang DW. Protein tyrosine nitration in atherosclerotic endothelial dysfunction. Clin Chim Acta. 2022;529:34–41.PubMedCrossRef

39.

Love KM, Barrett EJ, Malin SK, Reusch JEB, Rogensteiner JG, Liu Z. Diabetes pathogenesis and management: the endothelium comes of age. J Mol Cell Biol. 2021;13:500–12.PubMedPubMedCentralCrossRef

40.

Su X, Chen S, Liu J, Feng Y, Han E, Hao X, Liao M, Cai J, Zhang S, Niu J, He S, Huang S, Lo K, Zeng F. Composition of gut microbiota and non-alcoholic fatty liver disease: a systematic review and meta-analysis. Obes Rev. 2023;9: e13646.

41.

Jadhav PA, Thomas AB, Nanda RK, Chitlange SS. Unveiling the role of gut dysbiosis in non-alcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2023;35(12):1324–33.

42.

AL Samarraie A, Pichette M, Rousseau G. Role of the gut microbiome in the development of atherosclerotic cardiovascular disease. Int J Mol Sci. 2023;24:5420.PubMedPubMedCentralCrossRef

43.

Oktaviono YH, Dyah Lamara A, Saputra PBT, Arnindita JN, Pasahari D, Saputra ME, Suasti NMA. The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: a literature review. Biomol Biomed. 2023;23(6):936–48.

44.

Jing L, Zhang H, Xiang Q, Shen L, Guo X, Zhai C, Hu H. Targeting trimethylamine N-oxide: a new therapeutic strategy for alleviating atherosclerosis. Front Cardiovasc Med. 2022;9: 864600.PubMedPubMedCentralCrossRef

45.

Querio G, Antoniotti S, Geddo F, Levi R, Gallo MP. Modulation of endothelial function by TMAO, a gut microbiota-derived metabolite. Int J Mol Sci. 2023;24:5806.PubMedPubMedCentralCrossRef

46.

Bataller R, Sancho-Bru P, Ginès P, Lora JM, Al-Garawi A, Solé M, Colmenero J, Nicolás JM, Jiménez W, Weich N, Gutiérrez-Ramos JC, Arroyo V, Rodés J. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology. 2003;125:117–25.PubMedCrossRef

47.

Aminuddin A, Cheong SS, Roos NAC, Ugusman A. Smoking and unstable plaque in acute coronary syndrome: a systematic review of the role of matrix metalloproteinases. Int J Med Sci. 2023;20:482–92.PubMedPubMedCentralCrossRef

48.

Mantovani A, Csermely A, Petracca G, Beatrice G, Corey KE, Simon TG, Byrne CD, Targher G. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2021;6:903–13.PubMedCrossRef

49.

Koulaouzidis G, Charisopoulou D, Kukla M, Marlicz W, Rydzewska G, Koulaouzidis A, Skonieczna-Zydecka K. Association of non-alcoholic fatty liver disease with coronary artery calcification progression: a systematic review and meta-analysis. Prz Gastroenterology. 2021;16:196–206.

50.

Alon L, Corica B, Raparelli V, Cangemi R, Basili S, Proietti M, Romiti GF. Risk of cardiovascular events in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis. Eur J Prev Cardiol. 2022;29:938–46.PubMedCrossRef

51.

Lee H, Lee YH, Kim SU, Kim HC. Metabolic dysfunction-associated fatty liver disease and incident cardiovascular risk: a nationwide cohort study. Clin Gastroenterol Hepatol. 2021;19:2138–47.PubMedCrossRef

52.

Quek J, Ng CH, Tang ASP, Chew N, Chan M, Khoo CM, et al. Metabolic associated fatty liver disease increases the risk of systemic complications and mortality. A meta-analysis and systematic review of 12,620,736 individuals. Endocr Pract. 2022;28:667–72.PubMedCrossRef

53.

Fu CE, Ng CH, Yong JN, Chan KE, Xiao J, et al. A meta-analysis on associated risk of mortality in nonalcoholic fatty liver disease. Endocr Pract. 2023;29:33–9.PubMedCrossRef

54.

Bisaccia G, Ricci F, Khanji MY, Sorella A, Melchiorre E, et al. Cardiovascular morbidity and mortality related to non-alcoholic fatty liver disease: A systematic review and meta-analysis. Curr Probl Cardiol. 2023;48: 101643.PubMedCrossRef

55.

Jamalinia M, Zare F, Lankarani KB. Systematic review and meta-analysis: Association between liver fibrosis and subclinical atherosclerosis in nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2023;58:384–94.PubMedCrossRef

56.

Lauridsen BK, Stender S, Kristensen TS, Kofoed KF, Køber L, Nordestgaard BG, Tybjaerg-Hansen A. Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease: Mendelian randomization and meta-analysis of 279,013 individuals. Eur Heart J. 2018;39:385–93.PubMedCrossRef

57.

Brouwers MCGJ, Simons N, Stehouwer CDA, Koek GH, Schaper NC, Isascs A. Relationship between nonalcoholic fatty liver disease susceptibility genes and coronary artery disease. Hepatol Commun. 2019;3:587–96.PubMedPubMedCentralCrossRef

58.

Castillo-Núnez Y, Morales-Villegas E, Aguilar-Salinas CA. Triglyceride-rich lipoproteins: Their role in atherosclerosis. Rev Invest Clin. 2022;74:061–70.PubMed

59.

Björnson E, Samaras D, Adiels M, Kullberg J, Bäckhed F, Bergström G, Gummesson A. Mediating role of atherogenic lipoproteins in the relationship between liver fat and coronary artery calcification. Sci Rep. 2023;13:13217.PubMedPubMedCentralCrossRef

60.

••Björnson E, Adiels M, Bergström G, Gummesson A. The relationship between genetic liver fat and coronary heart disease is explained by apoB-containing lipoproteins. Atherosclerosis. 2024;388:117397. https://doi.org/10.1016/j.atherosclerosis.2023.117397. this is a genome-wide association study in the UK Biobank, using MR analyses, suggesting that the relationship between genetically-determinated liver fat and coronary heart disease is mediated by the causal effect of apoB.

61.

Ren Z, Simons PIHG, Wesselius A, Stehouwer CDA, Brouwers MCGJ. Relationship between NAFLD and coronary artery disease: A Mendelian randomization study. Hepatology. 2023;77:230–8.PubMedCrossRef

Titel: Metabolic dysfunction-associated steatotic liver disease and atherosclerosis
verfasst von: Yulino Castillo-Núñez
Paloma Almeda-Valdes
Guillermo González-Gálvez
María del Rosario Arechavaleta-Granell
Publikationsdatum: 03.05.2024
Verlag: Springer US
Erschienen in: Current Diabetes Reports
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-024-01542-6

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen