Cardiovascular Implications Of Metabolic Associated Fatty Liver Disease And Non-Alcoholic Fatty Liver Disease: An In-Depth Review
Keywords:
Metabolic Related Fatty Liver Illness, Cardiovascular diseases, and Endothelial dysfunction accurateAbstract
Background: Both Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Associated Fatty Liver Disease (MAFLD) are becoming more well acknowledged as common liver disorders associated with substantial metabolic dysfunction. These conditions, which are marked by hepatic steatosis without binge drinking, are linked to an increased risk of cardiovascular diseases (CVD), an area that has not received enough attention.
Objective: The objective of this study is to compile the most recent information on the cardiovascular effects of MAFLD and NAFLD, looking at their pathophysiological relationships, clinical outcomes, and possible treatment approaches.
Methods: We carried out an extensive assessment of the literature, concentrating on the relationship between MAFLD/NAFLD and cardiovascular health, based on research that were published during the last ten years. The effects on cardiovascular risk factors, the processes relating hepatic steatosis to vascular pathology, and the impact of various liver illnesses on clinical outcomes, such as mortality and cardiovascular events, are important topics of research.
Results: Through a number of processes, MAFLD and NAFLD are significantly linked to an elevated risk of cardiovascular disease. These comprise endothelial dysfunction, insulin resistance, dyslipidemia, and systemic inflammation. Increased risk of myocardial infarction, stroke, and heart failure, as well as accelerated atherosclerosis, have all been associated with the presence of hepatic steatosis. Furthermore, the metabolic syndrome that is frequently linked to chronic liver illnesses increases the risk of cardiovascular disease.
Conclusion: Important factors that contribute to cardiovascular morbidity and death are MAFLD and NAFLD. The necessity for integrated management techniques that address the hepatic and cardiovascular elements of patient care is highlighted by their influence on cardiovascular health. Subsequent investigations have to concentrate on clarifying the exact processes that connect these liver disorders with cardiovascular pathology and assessing the effectiveness of focused therapies to reduce related hazards.
Downloads
Metrics
References
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—metaanalytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64:73-84. doi:10.1002/hep.28431
Han E, Han KD, Lee YH, et al. Fatty Liver & Diabetes Statistics in Korea: Nationwide Data 2009 to 2017. Diabetes Metab J 2023; 47:347-55. doi:10.4093/dmj.2022.0444
Kim KS, Hong S, Ahn HY, Park CY. Metabolic dysfunction-associated fatty liver disease and mortality: a population-based cohort study. Diabetes Metab J 2023; 47:220-31. doi:10.4093/dmj.2021.0327
Mantovani A, Csermely A, Petracca G, et al. 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. doi:10.1016/S2468- 1253(21)00308-3
Wei J.L., Leung J.C.-F., Loong T.C.-W., Wong G.L.-H., Yeung D.K.-W., Chan R.S.-M., Chan H.L.-Y., Chim A.M.-L., Woo J., Chu W.C.-M., et al. Prevalence and Severity of Nonalcoholic Fatty Liver Disease in Non-Obese Patients: A Population Study Using Proton-Magnetic Resonance Spectroscopy. Am. J. Gastroenterol. 2015; 10:1306–1314doi: 10.1038/ajg.2015.235. quiz 1315. [PubMed] [CrossRef] [Google Scholar]
Sookoian S., Pirola C.J. Systematic review with meta-analysis: Risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients. Aliment. Pharmacol. Ther. 2017; 46:85–95. doi: 10.1111/apt.14112. [PubMed] [CrossRef] [Google Scholar]
Sookoian S., Pirola C.J. Systematic review with meta-analysis: The significance of histological disease severity in lean patients with nonalcoholic fatty liver disease. Aliment. Pharmacol. Ther. 2018; 47:16–25. doi: 10.1111/apt.14401. [PubMed] [CrossRef] [Google Scholar]
Pan J.J., Fallon M.B. Gender and racial differences in nonalcoholic fatty liver disease. World J. Hepatol. 2014;6 :274–283. doi: 10.4254/wjh.v6.i5.274. [PMC free article] [PubMed] [CrossRef] [Google Scholar].
Ogresta D., Mrzljak A., Berkovic M.C., Bilic-Curcic I., Stojsavljevic-Shapeski S., Virovic-Jukic L. Coagulation and Endothelial Dysfunction Associated with NAFLD: Current Status and Therapeutic Implications. J. Clin. Transl. Hepatol. 2022; 10:339–355. doi: 10.14218/JCTH.2021.00268. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Costa D.S., Guahnon M.P., Seganfredo F.B., Pinto L.P., Tovo C.V., Fernandes S.A. Vitamin B12 and Homocysteine Levels in Patients with Nafld: A Systematic Review and Metanalysis. Arq. Gastroenterol. 2021; 58:234–239. doi: 10.1590/s0004-2803. 202100000-42. [PubMed] [CrossRef] [Google Scholar]
Pacana T., Cazanave S.C., Verdianelli A., Patel V., Min H.-K., Mirshahi F., Quinlivan E.P., Sanyal A.J. Dysregulated Hepatic Methionine Metabolis Drives Homocysteine Elevation in Diet-Induced Nonalcoholic Fatty Liver Disease. PLoS ONE. 2015;10: e0136822. doi: 10.1371/journal.pone.0136822. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Stahl E.P., Dhindsa D.S., Lee S.K., Sandesara P.K., Chalasani N.P., Sperling L.S. Nonalcoholic Fatty Liver Disease and the Heart: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 2019; 73:948–963. doi: 10.1016/j.jacc.2018.11.050. [PubMed] [CrossRef] [Google Scholar]
Quek, Jingxuan 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 Endocrine Practice, Volume 28, Issue 7, 667 – 672
C.D. Byrne. Ectopic fat, insulin resistance and non-alcoholic fatty liver disease.Proc utr Soc, 72 (2013), pp. 412-419
C.D. Byrne. Dorothy Hodgkin Lecture 2012: non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management. Diabet Med, 29 (2012), pp. 1098-1107
W.Z. Mehal. The Gordian Knot of dysbiosis, obesity and NAFLD. Nat Rev Gastroenterol Hepatol, 10 (2013), pp. 637-644
M.J. Armstrong, L.A. Adams, A. Canbay, W.K. Syn. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology, 59 (2014), pp. 1174-1197
N. Stefan, H.U. Haring. The role of hepatokines in metabolism. Nat Rev Endocrinol, 9 (2013), pp. 144-152
G. Targher, C.D. Byrne. Diagnosis and management of nonalcoholic Fatty liver disease and its hemostatic/thrombotic and vascular complications.Semin Thromb Hemost, 39 2013), pp. 214-228
Gepner Y, Shelef I, Schwarzfuchs D et al (2018) Efect of distinct lifestyle interventions on mobilization of fat storage pools: CENTRAL magnetic resonance imaging randomized controlled trial. Circulation 137:1143–1157. https://doi.org/10.1161/CIRCU LATIONAHA.117.030501
Ipsen D, Lykkesfeldt J, Tveden-Nyborg P (2018) Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci 75:3313–3327. https://doi. org/10.1007/s00018-018-2860-6
Francque S, van der Graaf D, Kwanten W (2016) Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. J Hepatol 65:425–443. https://doi. org/10.1016/j.jhep.2016.04.005
Allen A, Therneau T, Larson J et al (2018) Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: a 20 year-community study. Hepatology 67:1726–1736. https://doi.org/10.1002/hep.29546
Lechner K, McKenzie A, Kränkel N et al (2020) High-risk atherosclerosis and metabolic phenotype: the roles of ectopic adiposity, atherogenic dyslipidemia, and infammation. Metab Syndr Relat Disord 18:176–185. https://doi.org/10.1089/met.2019.0115
Stahl E.P., Dhindsa D.S., Lee S.K., Sandesara P.K., Chalasani N.P., Sperling L.S. Nonalcoholic Fatty Liver Disease and the Heart: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 2019; 73:948–963. doi: 10.1016/j.jacc.2018.11.050. [PubMed] [CrossRef] [Google Scholar]
Francque S, van der Graaf D, Kwanten W (2016) Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. J Hepatol 65:425–443. https://doi. org/10.1016/j.jhep.2016.04.005
Cusi K (2012) Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology 142:711–725. https://doi. org/10.1053/j.gastro.2012.02.003
Lechner K, Lorenz E, Drezner J (2020) The “heart” of preventive cardiology: lifestyle medicine for the treatment of cardiometabolic diseases. Eur J Prev Cardiol 13:2047487319899107. https ://doi.org/10.1177/2047487319899107
Villanova N, Moscatiello S, Ramilli S et al (2005) Endothelial dysfunction and cardiovascular risk profle in nonalcoholic fatty liver disease. Hepatology 42:473–480. https://doi.org/10.1002/ hep.20781
Scholz G, Hanefeld M (2016) Metabolic vascular syndrome: new insights intoa multidimensional network of risk factors and diseases. Visc Med 32:319–326. https://doi.org/10.1159/000450866
Adiels M, Olofsson S, Taskinen M, Borén J (2008) Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arter Thromb Vasc Biol 28:1225–1236. https://doi.org/10.1161/ATVBAHA.107.160192
Stahl E, Dhindsa D, Lee S et al (2019) Nonalcoholic fatty liver disease and the heart: JACC state of the art review. J Am Coll Cardiol 73:948–963. https://doi.org/10.1016/j.jacc.2018.11.050
Francque S, van der Graaf D, Kwanten W (2016) Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. J Hepatol 65:425–443. https://doi. org/10.1016/j.jhep.2016.04.005
Shulman G (2014) Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med 371:1131–1141. https://doi.org/10.1056/NEJMra1011035
Petersen M, Shulman G (2018) Mechanisms of insulin action and insulin resistance. Physiol Rev 98:2133–2223. https://doi. org/10.1152/physrev.00063.2017
White M, Shaw J, Taylor R (2016) Type 2 diabetes: the pathologic basis of reversible β-cell dysfunction. Diabetes Care 39:2080–2088. https://doi.org/10.2337/dc16-0619
Low Wang C, Hess C, Hiatt W, Goldfne A (2016) Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus—mechanisms, management, and clinical considerations. Circulation 133:2459–2502. https://doi.org/10.1161/CIRCU LATIONAHA.116.022194
Agarwal S, Norby F, Whitsel E et al (2017) Cardiac autonomic dysfunction and incidence of atrial fbrillation in a large population-based cohort. J Am Coll Cardiol 69:291–299. https://doi. org/10.1016/j.jacc.2016.10.059
Anand S, Yi Q, Gerstein H et al (2003) Relationship of metabolic syndrome and fbrinolytic dysfunction to cardiovascular disease. Circulation 108:420–425. https://doi.org/10.1161/01.CIR.00000 80884.27358.49
Laakso M, Kuusisto J (2014) Insulin resistance and hyperglycaemia in cardiovascular disease development. Nat Rev Endocrinol 10:293–302. https://doi.org/10.1038/nrendo.2014.29
Pastore A, Alisi A, di Giovamberardino G et al (2014) Plasma levels of homocysteine and cysteine increased in pediatric nafd and strongly correlated with severity of liver damage. Int J Mol Sci 15:21202–21214. https://doi.org/10.3390/ijms151121202
de Carvalho S, Muniz M, Siqueira M et al (2013) Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease (NAFLD). Nutr J 12:37. https://doi.org/10.1186/1475-2891-12-37
Xu Y, Guan Y, Yang X et al (2020) Association of serum homocysteine levels with histological severity of NAFLD. J Gastrointestin Liver Dis 29:51–58. https://doi.org/10.15403/jgld-529
Ergatoudes C, Schaufelberger M, Andersson B et al (2019) Non-cardiac comorbidities and mortality in patients with heart failure with reduced vs. preserved ejection fraction: a study using the swedish heart failure registry. Clin Res Cardiol 108:1025–1033. https://doi.org/10.1007/s00392-019-01430-0
Zhou Y, Li Y, Nie Y et al (2012) Natural course of nonalcoholic fatty liver disease in southern china: a prospective cohort study. J Dig Dis 13:153–160. https://doi.org/10.111 1/j.1751-2980.2011.00571.x
Söderberg C, Stål P, Askling J et al (2010) Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 51:595–602. https://doi.org/10.1002/ hep.23314
Zeb I, Li D, Budof M et al (2016) Nonalcoholic fatty liver disease and incident cardiac events: the multi-ethnic study of atherosclerosis. J Am Coll Cardiol 67:1965–1966. https://doi. org/10.1016/j.jacc.2016.01.070
Suo-wen Xu 1, Iqra Ilyas1 and Jian-ping Weng 1. Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies. Acta Pharmacologica Sinica (2023) 44:695 – 709.
Wong C, Lim J (2018) The association between nonalcoholic fatty liver disease and cardiovascular disease outcomes. Clin Liver Dis 12:39–44. https://doi.org/10.1002/cld.721
Ekstedt M, Hagström H, Nasr P et al (2015) Fibrosis stage is the strongest predictor for disease-specifc mortality in NAFLD after up to 33 years of follow-up. Hepatology 61:1547–1554. https://doi.org/10.1002/hep.27368
Kim D, Kim W, Kim H, Therneau T (2013) Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 57:1357–1365. https://doi.org/10.1002/hep.26156
Lazo M, Hernaez R, Bonekamp S et al (2011) Non-alcoholic Fatty liver disease and mortality among us adults: prospective cohort study. BMJ 343:d6891. https://doi.org/10.1136/bmj. d6891
Adams L, Anstee Q, Tilg H, Targher G (2017) Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 66:1138–1153. https://doi. org/10.1136/gutjnl-2017-313884
Targher G, Byrne C, Lonardo A et al (2016) Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol 65:589–600. https://doi.org/10.1016/j. jhep.2016.05.013
Oni E, Agatston A, Blaha M et al (2013) A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis 230:258–267. https://doi.org/10.1016/j.atherosclerosis .2013.07.052
Mantovani A, Mingolla L, Rigolon R et al (2016) nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular disease in adult patients with type
Zhou Y, Zhou X, Wu S et al (2018) Synergistic increase in cardiovascular risk in diabetes mellitus with nonalcoholic fatty liver disease: a meta-analysis. Eur J Gastroenterol Hepatol 30:631– 636. https://doi.org/10.1097/MEG.0000000000001075
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
