Skip to content
2000
image of Metabolic Dysfunction-Associated Steatotic Liver Disease and Peripheral Arterial Disease: Associations and Treatment Considerations

Abstract

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) and peripheral arterial disease (PAD) are highly prevalent conditions that increase cardiovascular risk. This review aims to summarize current evidence on the association between MASLD and PAD, with a particular focus on clinical studies. A critical appraisal of this association will enhance understanding of MASLD as a multi-system disease and provide potential therapeutic implications.

Methods

A literature search was performed using the PubMed database.

Results

Both MASLD and PAD are multifactorial diseases that share common risk factors and pathogenic mechanisms. Most relevant clinical studies support an association between MASLD and PAD, particularly in the context of hepatic steatosis. Data regarding steatohepatitis or hepatic fibrosis are limited, largely due to the scarcity of studies with biopsy-proven MASLD. Management strategies for MASLD and PAD overlap, emphasizing lifestyle modifications such as a balanced diet, regular exercise, and smoking cessation. Additionally, certain medications used for PAD (., statins, aspirin) or under investigation for MASLD (., glucagon-like peptide-1 receptor agonists, dual and triple peptide agonists) may have beneficial effects on both conditions.

Discussion

Until clinical trials specifically evaluate medications for patients with concomitant MASLD and PAD, priority should be given to lifestyle interventions and the management of shared comorbidities, including obesity, type 2 diabetes mellitus, arterial hypertension, and dyslipidemia, which may confer benefits for both diseases.

Conclusions

MASLD and PAD frequently coexist. Targeting both conditions is expected to reduce the elevated cardiovascular risk observed in patients affected by both MASLD and PAD.

© 2026 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cvp/10.2174/0115701611414052251127074106
2026-01-15
2026-02-06

  • From This Site

    /content/journals/cvp/10.2174/0115701611414052251127074106
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Boutari C. Polyzos S.A. Mantzoros C.S. Addressing the epidemic of fatty liver disease: A call to action, a call to collaboration, a call to moving the field forward. Metabolism 2021 122 154781 10.1016/j.metabol.2021.154781 33901501
    [Google Scholar]
  2. Vachliotis I. Goulas A. Papaioannidou P. Polyzos S.A. Nonalcoholic fatty liver disease: Lifestyle and quality of life. Hormones (Athens) 2022 21 1 41 49 10.1007/s42000‑021‑00339‑6 34854066
    [Google Scholar]
  3. Polyzos S.A. Kechagias S. Tsochatzis E.A. Review article: Non‐alcoholic fatty liver disease and cardiovascular diseases: Associations and treatment considerations. Aliment. Pharmacol. Ther. 2021 54 8 1013 1025 10.1111/apt.16575 34416040
    [Google Scholar]
  4. Ekstedt M. Hagström H. Nasr P. 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 1554 10.1002/hep.27368 25125077
    [Google Scholar]
  5. Wen W. Fan H. Zhang S. Associations between metabolic dysfunction-associated fatty liver disease and atherosclerotic cardiovascular disease. Am. J. Med. Sci. 2024 368 6 557 568 10.1016/j.amjms.2024.06.022 38944203
    [Google Scholar]
  6. Calling S. Ji J. Sundquist J. Sundquist K. Zöller B. Shared and non-shared familial susceptibility of coronary heart disease, ischemic stroke, peripheral artery disease and aortic disease. Int. J. Cardiol. 2013 168 3 2844 2850 10.1016/j.ijcard.2013.03.149 23642611
    [Google Scholar]
  7. Adou C. Magne J. Gazere N. Aouida M. Chastaingt L. Aboyans V. Global epidemiology of lower extremity artery disease in the 21st century (2000–21): a systematic review and meta-analysis. Eur. J. Prev. Cardiol. 2024 31 7 803 811 10.1093/eurjpc/zwad381 38079162
    [Google Scholar]
  8. Song P. Rudan D. Zhu Y. Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: An updated systematic review and analysis. Lancet Glob. Health 2019 7 8 e1020 e1030 10.1016/S2214‑109X(19)30255‑4 31303293
    [Google Scholar]
  9. Athyros V.G. Polyzos S.A. Kountouras J. Non-alcoholic fatty liver disease treatment in patients with type 2 diabetes mellitus; new kids on the block. Curr. Vasc. Pharmacol. 2020 18 2 172 181 10.2174/1570161117666190405164313 30961499
    [Google Scholar]
  10. Athyros V.G. Alexandrides T.K. Bilianou H. The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement. Metabolism 2017 71 17 32 10.1016/j.metabol.2017.02.014 28521870
    [Google Scholar]
  11. Gornik H.L. Aronow H.D. Goodney P.P. 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the management of lower extremity peripheral artery disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2024 149 24 e1313 e1410 10.1161/CIR.0000000000001251 38743805
    [Google Scholar]
  12. Rinella M.E. Lazarus J.V. Ratziu V. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J. Hepatol. 2023 79 6 1542 1556 10.1016/j.jhep.2023.06.003 37364790
    [Google Scholar]
  13. Polyzos S. Kountouras J. Zavos C. Nonalcoholic fatty liver disease: The pathogenetic roles of insulin resistance and adipocytokines. Curr. Mol. Med. 2009 9 3 299 314 10.2174/156652409787847191 19355912
    [Google Scholar]
  14. Makri E. Goulas A. Polyzos S.A. Epidemiology, Pathogenesis, Diagnosis and Emerging Treatment of Nonalcoholic Fatty Liver Disease. Arch. Med. Res. 2021 52 1 25 37 10.1016/j.arcmed.2020.11.010 33334622
    [Google Scholar]
  15. Fowkes F.G.R. Rudan D. Rudan I. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: A systematic review and analysis. Lancet 2013 382 9901 1329 1340 10.1016/S0140‑6736(13)61249‑0 23915883
    [Google Scholar]
  16. Jung H.S. Chang Y. Kwon M.J. Smoking and the risk of non-alcoholic fatty liver disease: A cohort study. Am. J. Gastroenterol. 2019 114 3 453 463 10.1038/s41395‑018‑0283‑5 30353055
    [Google Scholar]
  17. Yuan S. Chen J. Ruan X. Smoking, alcohol consumption, and 24 gastrointestinal diseases: Mendelian randomization analysis. eLife 2023 12 e84051 10.7554/eLife.84051 36727839
    [Google Scholar]
  18. Marti-Aguado D. Clemente-Sanchez A. Bataller R. Cigarette smoking and liver diseases. J. Hepatol. 2022 77 1 191 205 10.1016/j.jhep.2022.01.016 35131406
    [Google Scholar]
  19. Petrick J.L. Campbell P.T. Koshiol J. Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project. Br. J. Cancer 2018 118 7 1005 1012 10.1038/s41416‑018‑0007‑z 29520041
    [Google Scholar]
  20. Park S.H. Jeon W.K. Kim S.H. Prevalence and risk factors of non‐alcoholic fatty liver disease among Korean adults. J. Gastroenterol. Hepatol. 2006 21 1 138 143 10.1111/j.1440‑1746.2005.04086.x 16706825
    [Google Scholar]
  21. Ciccone M.M. Bilianou E. Balbarini A. Task force on. J. Cardiovasc. Med. (Hagerstown) 2013 14 10 757 766 10.2459/JCM.0b013e328362078d 24335886
    [Google Scholar]
  22. Mo H. Yue P. Li Q. The role of liver sinusoidal endothelial cells in metabolic dysfunction-associated steatotic liver diseases and liver cancer: Mechanisms and potential therapies. Angiogenesis 2025 28 2 14 10.1007/s10456‑025‑09969‑5 39899173
    [Google Scholar]
  23. Baumgartner-Parzer S Waldhäusl W The endothelium as a metabolic and endocrine organ: Its relation with insulin resistance. Exp Clin Endocrinol Diabetes 2001 109 S166 79 (Suppl. 2) 10.1055/s‑2001‑18579 11460568
    [Google Scholar]
  24. Habib A. Petrucci G. Rocca B. Pathophysiology of thrombosis in peripheral artery disease. Curr. Vasc. Pharmacol. 2020 18 3 204 214 10.2174/1570161117666190206234046 30727897
    [Google Scholar]
  25. Alsharoh H. Ismaiel A. Leucuta D.C. Popa S.L. Dumitrascu D.L. Plasminogen activator inhibitor-1 levels in non-alcoholic fatty liver disease: A systematic review and meta-analysis. J. Gastrointestin. Liver Dis. 2022 31 2 206 214 10.15403/jgld‑4091 35574617
    [Google Scholar]
  26. Degertekin B. Ozenirler S. Elbeg S. Akyol G. The serum endothelin-1 level in steatosis and NASH, and its relation with severity of liver fibrosis. Dig. Dis. Sci. 2007 52 10 2622 2628 10.1007/s10620‑006‑9147‑8 17429733
    [Google Scholar]
  27. Matiy V.V. Rishko M.V. Rosola T.F. Hadzheha V.M. Stan M.P. Tsoka S.A. Biomarker diagnostics of endothelial dysfunction in patients with acute coronary syndrome and non-alcoholic fatty liver disease. Wiad. Lek. 2024 77 10 1857 1862 10.36740/WLek/195126 39661874
    [Google Scholar]
  28. Vinciguerra M. Nitric oxide as a protector from nonalcoholic fatty liver disease. Hepatology 2015 61 6 2115 2116 10.1002/hep.27562 25308328
    [Google Scholar]
  29. Blinc A. Paraskevas K.I. Stanek A. Diet and exercise in relation to lower extremity artery disease. Int. Angiol. 2024 43 4 458 467 10.23736/S0392‑9590.24.05310‑0 39463151
    [Google Scholar]
  30. Pugh C.J.A. Cuthbertson D.J. Sprung V.S. Exercise training improves cutaneous microvascular function in nonalcoholic fatty liver disease. Am. J. Physiol. Endocrinol. Metab. 2013 305 1 E50 E58 10.1152/ajpendo.00055.2013 23651847
    [Google Scholar]
  31. Laivuori M. Biancari F. Sinisalo J. Statin use improves survival of patients with known or suspected lower extremity artery disease on all ankle brachial index levels. Vasa 2023 52 1 54 62 10.1024/0301‑1526/a001041 36458408
    [Google Scholar]
  32. Wang W. Zhao C. Zhou J. Zhen Z. Wang Y. Shen C. Simvastatin ameliorates liver fibrosis via mediating nitric oxide synthase in rats with non-alcoholic steatohepatitis-related liver fibrosis. PLoS One 2013 8 10 e76538 10.1371/journal.pone.0076538 24098525
    [Google Scholar]
  33. Polyzos S.A. Kountouras J. Mantzoros C.S. Adipose tissue, obesity and non-alcoholic fatty liver disease. Minerva Endocrinol. 2017 42 2 92 108 27711029
    [Google Scholar]
  34. Stefan N. Schick F. Birkenfeld A.L. Häring H.U. White M.F. The role of hepatokines in NAFLD. Cell Metab. 2023 35 2 236 252 10.1016/j.cmet.2023.01.006 36754018
    [Google Scholar]
  35. Libby P. Ridker P.M. Hansson G.K. Progress and challenges in translating the biology of atherosclerosis. Nature 2011 473 7347 317 325 10.1038/nature10146 21593864
    [Google Scholar]
  36. Chen M. Masaki T. Sawamura T. LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis. Pharmacol. Ther. 2002 95 1 89 100 10.1016/S0163‑7258(02)00236‑X 12163130
    [Google Scholar]
  37. Zhang Q. Li F. Ritchie R.H. Woodman O.L. Zhou X. Qin C.X. Novel strategies to promote resolution of inflammation to treat lower extremity artery disease. Curr. Opin. Pharmacol. 2022 65 102263 10.1016/j.coph.2022.102263 35802962
    [Google Scholar]
  38. Tziomalos K. Athyros V.G. Karagiannis A. Non-alcoholic fatty liver disease in type 2 diabetes: pathogenesis and treatment options. Curr. Vasc. Pharmacol. 2012 10 2 162 172 10.2174/157016112799305012 22239625
    [Google Scholar]
  39. Mozos I. Luca C.T. Crosstalk between Oxidative and Nitrosative Stress and Arterial Stiffness. Curr. Vasc. Pharmacol. 2017 15 5 446 456 28155616
    [Google Scholar]
  40. Signorelli S.S. Katsiki N. Oxidative Stress and Inflammation: Their Role in the Pathogenesis of Peripheral Artery Disease with or Without Type 2 Diabetes Mellitus. Curr. Vasc. Pharmacol. 2018 16 6 547 554 10.2174/1570161115666170731165121 28762307
    [Google Scholar]
  41. Abosheaishaa H. Hussein M. Ghallab M. Association between non-alcoholic fatty liver disease and coronary artery disease outcomes: A systematic review and meta-analysis. Diabetes Metab. Syndr. 2024 18 1 102938 10.1016/j.dsx.2023.102938 38194827
    [Google Scholar]
  42. Sullivan J.L. Iron in arterial plaque: A modifiable risk factor for atherosclerosis. Biochim. Biophys. Acta, Gen. Subj. 2009 1790 7 718 723 10.1016/j.bbagen.2008.06.005 18619522
    [Google Scholar]
  43. Makri E. Orfanidou M. Makri E.S. Goulas A. Terpos E. Polyzos S.A. Circulating ferritin in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis. J. Clin. Exp. Hepatol. 2024 14 3 101353 10.1016/j.jceh.2024.101353 38435724
    [Google Scholar]
  44. Yu Q. Song L. Unveiling the role of ferroptosis in the progression from NAFLD to NASH: recent advances in mechanistic understanding. Front. Endocrinol. (Lausanne) 2024 15 1431652 10.3389/fendo.2024.1431652 39036052
    [Google Scholar]
  45. Tilg H. Adolph T.E. Trauner M. Gut-liver axis: Pathophysiological concepts and clinical implications. Cell Metab. 2022 34 11 1700 1718 10.1016/j.cmet.2022.09.017 36208625
    [Google Scholar]
  46. Flori L. Benedetti G. Martelli A. Calderone V. Microbiota alterations associated with vascular diseases: postbiotics as a next-generation magic bullet for gut-vascular axis. Pharmacol. Res. 2024 207 107334 10.1016/j.phrs.2024.107334 39103131
    [Google Scholar]
  47. Meijnikman A.S. Davids M. Herrema H. Microbiome-derived ethanol in nonalcoholic fatty liver disease. Nat. Med. 2022 28 10 2100 2106 10.1038/s41591‑022‑02016‑6 36216942
    [Google Scholar]
  48. Yuan S. Wu J. Chen J. Association between alcohol consumption and peripheral artery disease: two de novo prospective cohorts and a systematic review with meta-analysis. Eur. J. Prev. Cardiol. 2025 32 2 149 155 10.1093/eurjpc/zwae142 38626304
    [Google Scholar]
  49. Juanola O. Ferrusquía-Acosta J. García-Villalba R. Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis. FASEB J. 2019 33 10 11595 11605 10.1096/fj.201901327R 31345057
    [Google Scholar]
  50. May K.S. den Hartigh L.J. Gut Microbial-Derived Short Chain Fatty Acids: Impact on Adipose Tissue Physiology. Nutrients 2023 15 2 272 10.3390/nu15020272 36678142
    [Google Scholar]
  51. Sookoian S. Rotman Y. Valenti L. Genetics of Metabolic Dysfunction-associated Steatotic Liver Disease: The State of the Art Update. Clin. Gastroenterol. Hepatol. 2024 22 11 2177 2187 10.1016/j.cgh.2024.05.052 39094912
    [Google Scholar]
  52. Polyzos S.A. Bugianesi E. Kountouras J. Mantzoros C.S. Nonalcoholic fatty liver disease: Updates on associations with the metabolic syndrome and lipid profile and effects of treatment with PPAR-γ agonists. Metabolism 2017 66 64 68 10.1016/j.metabol.2016.08.001 27594084
    [Google Scholar]
  53. Wu J.T. Liu S.S. Xie X.J. Liu Q. Xin Y.N. Xuan S.Y. Independent and joint correlation of PNPLA3 I148M and TM6SF2 E167K variants with the risk of coronary heart disease in patients with non-alcoholic fatty liver disease. Lipids Health Dis. 2020 19 1 29 10.1186/s12944‑020‑01207‑9 32093693
    [Google Scholar]
  54. Rüschenbaum S. Schwarzkopf K. Friedrich-Rust M. Patatin‐like phospholipase domain containing 3 variants differentially impact metabolic traits in individuals at high risk for cardiovascular events. Hepatol. Commun. 2018 2 7 798 806 10.1002/hep4.1183 30027138
    [Google Scholar]
  55. Holmen O.L. Zhang H. Fan Y. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk. Nat. Genet. 2014 46 4 345 351 10.1038/ng.2926 24633158
    [Google Scholar]
  56. Dongiovanni P. Petta S. Maglio C. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 2015 61 2 506 514 10.1002/hep.27490 25251399
    [Google Scholar]
  57. Polyzos S.A. Kountouras J. Zavos C. Deretzi G. Nonalcoholic fatty liver disease: multimodal treatment options for a pathogenetically multiple-hit disease. J. Clin. Gastroenterol. 2012 46 4 272 284 10.1097/MCG.0b013e31824587e0 22395062
    [Google Scholar]
  58. Lv Q. Han Q. Wen Z. Pan Y. Chen J. The association between atherosclerosis and nonalcoholic fatty liver disease. Medicine (Baltimore) 2024 103 1 e36815 10.1097/MD.0000000000036815 38181273
    [Google Scholar]
  59. Wang L. Li Y. Gong X. Changes in inflammatory factors and prognosis of patients complicated with non-alcoholic fatty liver disease undergoing coronary artery bypass grafting. Exp. Ther. Med. 2018 15 1 949 953 29434690
    [Google Scholar]
  60. Makri E.S. Makri E. Polyzos S.A. Combination Therapies for Nonalcoholic Fatty Liver Disease. J. Pers. Med. 2022 12 7 1166 10.3390/jpm12071166 35887662
    [Google Scholar]
  61. Cholongitas E. Tsilingiris D. Diamantopoulou P. Association of cardiovascular factors in diabetic patients with non-alcoholic fatty liver disease. Hormones (Athens) 2022 21 1 133 145 10.1007/s42000‑021‑00334‑x 34716911
    [Google Scholar]
  62. Ciardullo S. Bianconi E. Cannistraci R. Parmeggiani P. Marone E.M. Perseghin G. Peripheral artery disease and all-cause and cardiovascular mortality in patients with NAFLD. J. Endocrinol. Invest. 2022 45 8 1547 1553 10.1007/s40618‑022‑01792‑9 35364761
    [Google Scholar]
  63. Denimal D. Ponnaiah M. Phan F. Metabolic dysfunction-associated steatotic liver disease (MASLD) biomarkers and progression of lower limb arterial calcification in patients with type 2 diabetes: A prospective cohort study. Cardiovasc. Diabetol. 2025 24 1 176 10.1186/s12933‑025‑02705‑9 40269920
    [Google Scholar]
  64. Huang X. Li Z. Zhai Z. Association between metabolic dysfunction-associated fatty liver disease and macces in patients with diabetic foot ulcers: An ambispective longitudinal cohort study. Diabetes Metab. Syndr. Obes. 2024 17 1119 1130 10.2147/DMSO.S447897 38465347
    [Google Scholar]
  65. Labenz C. Kostev K. Alqahtani S.A. Galle P.R. Schattenberg J.M. Impact of non-alcoholic fatty liver disease on metabolic comorbidities in type 2 diabetes mellitus. Exp. Clin. Endocrinol. Diabetes 2022 130 3 172 177 10.1055/a‑1378‑4679 33601426
    [Google Scholar]
  66. Liu Y. Wang J. Jin R. Associations of metabolic dysfunction–associated fatty liver disease with peripheral artery disease: Prospective analysis in the UK biobank and ARIC study. J. Am. Heart Assoc. 2024 13 22 e035265 10.1161/JAHA.124.035265 39547959
    [Google Scholar]
  67. Mertens J. Weyler J. Dirinck E. Increased prevalence and risk of atherosclerotic cardiovascular disease in individuals with Type 1 diabetes and metabolic dysfunction-associated steatotic liver disease. Cardiovasc. Diabetol. 2025 24 1 230 10.1186/s12933‑025‑02764‑y 40442720
    [Google Scholar]
  68. Meyhöfer S. Eckert A.J. Hummel M. Elevated liver enzymes and comorbidities in type 2 diabetes: A multicentre analysis of 51 645 patients from the Diabetes Prospective Follow‐up (DPV) database. Diabetes Obes. Metab. 2022 24 4 727 732 10.1111/dom.14616 34882949
    [Google Scholar]
  69. Ponziani F.R. Nesci A. Caputo C. High prevalence of lower limb atherosclerosis is linked with the gut–liver axis in patients with primary biliary cholangitis. Liver Int. 2023 43 2 370 380 10.1111/liv.15463 36287108
    [Google Scholar]
  70. Song X.H. Liu B. Lei F. The association between metabolic dysfunction-associated fatty liver disease and peripheral arterial disease in the chinese population. Diabetes Metab. Syndr. Obes. 2023 16 373 384 10.2147/DMSO.S394414 36798909
    [Google Scholar]
  71. Taharboucht S. Guermaz R. Brouri M. Bengherbia L. Chibane A. Ankle systolic pressure index in non-diabetic non-alcoholic fatty liver disease: A case-control study. J. Med. Vasc. 2023 48 5-6 154 162 10.1016/j.jdmv.2023.10.006 38035921
    [Google Scholar]
  72. Targher G. Bertolini L. Padovani R. Increased prevalence of cardiovascular disease in Type 2 diabetic patients with non‐alcoholic fatty liver disease. Diabet. Med. 2006 23 4 403 409 10.1111/j.1464‑5491.2006.01817.x 16620269
    [Google Scholar]
  73. Targher G. Bertolini L. Padovani R. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007 30 5 1212 1218 10.2337/dc06‑2247 17277038
    [Google Scholar]
  74. Targher G. Bertolini L. Padovani R. Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease in patients with type 1 diabetes. J. Hepatol. 2010 53 4 713 718 10.1016/j.jhep.2010.04.030 20619918
    [Google Scholar]
  75. Targher G. Pichiri I. Zoppini G. Trombetta M. Bonora E. Increased prevalence of cardiovascular disease in Type 1 diabetic patients with non-alcoholic fatty liver disease. J. Endocrinol. Invest. 2012 35 5 535 540 21795844
    [Google Scholar]
  76. Zhang C. Ying Y. Ru Y. Association between FIB-4 index and lower extremity arterial disease in MASLD patients: A cross-sectional study. Lipids Health Dis. 2025 24 1 103 10.1186/s12944‑025‑02516‑7 40114160
    [Google Scholar]
  77. Zhu W. Deng C.J. Xuan L.P. Peripheral artery disease and risk of fibrosis deterioration in nonalcoholic fatty liver disease: A prospective investigation. Biomed. Environ. Sci. 2020 33 4 217 226 32438959
    [Google Scholar]
  78. Zou Y. Li X. Wang C. Association between non‐alcoholic fatty liver disease and peripheral artery disease in patients with type 2 diabetes. Intern. Med. J. 2017 47 10 1147 1153 10.1111/imj.13549 28696562
    [Google Scholar]
  79. Kechagias S. Ekstedt M. Simonsson C. Nasr P. Non-invasive diagnosis and staging of non-alcoholic fatty liver disease. Hormones (Athens) 2022 21 3 349 368 10.1007/s42000‑022‑00377‑8 35661987
    [Google Scholar]
  80. Polyzos S.A. Mantzoros C.S. Necessity for timely noninvasive diagnosis of nonalcoholic fatty liver disease. Metabolism 2014 63 2 161 167 10.1016/j.metabol.2013.10.010 24290839
    [Google Scholar]
  81. Mintziori G. Polyzos S.A. Emerging and future therapies for nonalcoholic steatohepatitis in adults. Expert Opin. Pharmacother. 2016 17 14 1937 1946 10.1080/14656566.2016.1225727 27564402
    [Google Scholar]
  82. Polyzos S.A. Targher G. Hepatic thyroid hormone receptor‐β signalling: Mechanisms and recent advancements in the treatment of metabolic dysfunction‐associated steatohepatitis. Diabetes Obes. Metab. 2025 27 4 1635 1647 10.1111/dom.16117 39658733
    [Google Scholar]
  83. Conte M.S. Bradbury A.W. Kolh P. Global vascular guidelines on the management of chronic limb-threatening ischemia. J. Vasc. Surg. 2019 69 6S S3 S125 10.1016/j.jvs.2019.02.016 31159978
    [Google Scholar]
  84. Mahé G. Boge G. Bura-Rivière A. Disparities Between International Guidelines (AHA/ESC/ESVS/ESVM/SVS) concerning lower extremity arterial disease: Consensus of the french society of vascular medicine (SFMV) and the french society for vascular and endovascular surgery (SCVE). Ann. Vasc. Surg. 2021 72 1 56 10.1016/j.avsg.2020.11.011 33359707
    [Google Scholar]
  85. Pilitsi E. Farr O.M. Polyzos S.A. Pharmacotherapy of obesity: Available medications and drugs under investigation. Metabolism 2019 92 170 192 10.1016/j.metabol.2018.10.010 30391259
    [Google Scholar]
  86. Tacke F. Horn P. Wong V.W-S. EASL–EASD–EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD): Executive summary. Diabetologia 2024 67 11 2375 2392 10.1007/s00125‑024‑06196‑3 38869512
    [Google Scholar]
  87. Haas T.L. Lloyd P.G. Yang H.T. Terjung R.L. Exercise training and peripheral arterial disease. Compr. Physiol. 2012 2 4 2933 3017 10.1002/j.2040‑4603.2012.tb00473.x 23720270
    [Google Scholar]
  88. Younossi Z.M. Zelber-Sagi S. Lazarus J.V. Global consensus recommendations for metabolic dysfunction-associated steatotic liver disease and steatohepatitis. Gastroenterology 2025 169 5 1017 1032 10.1053/j.gastro.2025.02.044 40222485
    [Google Scholar]
  89. Polyzos S.A. Kountouras J. Mantzoros C.S. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism 2019 92 82 97 10.1016/j.metabol.2018.11.014 30502373
    [Google Scholar]
  90. Xu Z. Chuo J. Zhao X. Effectiveness of home-based walking exercise for patients with peripheral artery disease and intermittent claudication: A systematic review and meta-analysis. BMJ Open 2025 15 1 e086013 10.1136/bmjopen‑2024‑086013 39755577
    [Google Scholar]
  91. Arnett D.K. Blumenthal R.S. Albert M.A. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019 140 11 e596 e646 10.1161/CIR.0000000000000678 30879355
    [Google Scholar]
  92. Zhang S. Liu Z. Yang Q. Impact of smoking cessation on non-alcoholic fatty liver disease prevalence: a systematic review and meta-analysis. BMJ Open 2023 13 12 e074216 10.1136/bmjopen‑2023‑074216 38072477
    [Google Scholar]
  93. Vliegenthart R. Geleijnse J.M. Hofman A. Alcohol consumption and risk of peripheral arterial disease: The Rotterdam study. Am. J. Epidemiol. 2002 155 4 332 338 10.1093/aje/155.4.332 11836197
    [Google Scholar]
  94. Sookoian S. Castaño G.O. Pirola C.J. Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals. Gut 2014 63 3 530 532 10.1136/gutjnl‑2013‑305718 24026352
    [Google Scholar]
  95. Tsiampali C. Papaioannidou P. Goulas A. Polyzos S.A. The role of glucagon-like peptide-1 receptor agonists in nonalcoholic fatty liver disease. Expert Rev. Clin. Pharmacol. 2023 16 11 1063 1072 10.1080/17512433.2023.2274536 37864548
    [Google Scholar]
  96. Armstrong M.J. Gaunt P. Aithal G.P. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): A multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016 387 10019 679 690 10.1016/S0140‑6736(15)00803‑X 26608256
    [Google Scholar]
  97. Newsome P.N. Buchholtz K. Cusi K. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N. Engl. J. Med. 2021 384 12 1113 1124 10.1056/NEJMoa2028395 33185364
    [Google Scholar]
  98. Celsa C. Pennisi G. Tulone A. Glucagon-like peptide-1 receptor agonist use is associated with a lower risk of major adverse liver-related outcomes: A meta-analysis of observational cohort studies. Gut 2025 74 5 815 824 10.1136/gutjnl‑2024‑334591 40015951
    [Google Scholar]
  99. Lin Y.M. Wu J.Y. Lee M.C. Comparative cardiovascular effectiveness of glucagon-like peptide-1 receptor agonists and sodium–glucose cotransporter-2 inhibitors in atherosclerotic cardiovascular disease phenotypes: A systematic review and meta-analysis. Eur. Heart J. Cardiovasc. Pharmacother. 2025 11 2 174 189 10.1093/ehjcvp/pvae093 39923808
    [Google Scholar]
  100. Ashraf M.T. Ali A. Ahmed N. Shakeel Khan M.K. Usman M. Cardiovascular safety of glucagon-like receptor 1 agonists in patients with type 2 diabetes and peripheral arterial disease: A meta-analysis of randomized controlled trials. Am. J. Ther. 2024 31 4 e483 e486 10.1097/MJT.0000000000001689 38976535
    [Google Scholar]
  101. Polyzos S.A. Frühbeck G. Kiortsis D.N. Peptide polyagonists for the treatment of nonalcoholic fatty liver disease. Curr. Pharm. Des. 2023 29 41 3263 3265 10.2174/0113816128279822231211101522 38111116
    [Google Scholar]
  102. Polyzos S.A. Goulas A. Papaioannidou P. Tirzepatide for diabetes and obesity: A new window to the treatment of non-alcoholic steatohepatitis. Curr. Med. Chem. 2023 30 22 2476 2479 10.2174/0929867330666230106103202 36617715
    [Google Scholar]
  103. Loomba R. Hartman M.L. Lawitz E.J. Tirzepatide for Metabolic dysfunction–associated steatohepatitis with liver fibrosis. N. Engl. J. Med. 2024 391 4 299 310 10.1056/NEJMoa2401943 38856224
    [Google Scholar]
  104. Sanyal A.J. Bedossa P. Fraessdorf M. A phase 2 randomized trial of survodutide in MASH and fibrosis. N. Engl. J. Med. 2024 391 4 311 319 10.1056/NEJMoa2401755 38847460
    [Google Scholar]
  105. Sanyal A.J. Kaplan L.M. Frias J.P. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: A randomized phase 2a trial. Nat. Med. 2024 30 7 2037 2048 10.1038/s41591‑024‑03018‑2 38858523
    [Google Scholar]
  106. Wu J.Y. Tu W.L. Yu T. Liao K.M. Lin Y.M. Tirzepatide and major adverse limb events: Insights from a multicenter real-world analysis in PAD and diabetes patients. Diabetes Res. Clin. Pract. 2025 222 112083 10.1016/j.diabres.2025.112083 40049522
    [Google Scholar]
  107. Drucker D.J. GLP-1-based therapies for diabetes, obesity and beyond. Nat. Rev. Drug Discov. 2025 24 8 631 650 10.1038/s41573‑025‑01183‑8 40281304
    [Google Scholar]
  108. Upadhyay J. Polyzos S.A. Perakakis N. Pharmacotherapy of type 2 diabetes: An update. Metabolism 2018 78 13 42 10.1016/j.metabol.2017.08.010 28920861
    [Google Scholar]
  109. Makri E.S. Goulas A. Polyzos S.A. Sodium-glucose co-transporter 2 inhibitors in nonalcoholic fatty liver disease. Eur. J. Pharmacol. 2021 907 174272 10.1016/j.ejphar.2021.174272 34147478
    [Google Scholar]
  110. Li H. Hou Y. Xin W. The efficacy of sodium-glucose transporter 2 inhibitors in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis. Pharmacol. Res. 2025 213 107647 10.1016/j.phrs.2025.107647 39929274
    [Google Scholar]
  111. Ong Lopez A.M.C. Pajimna J.A.T. Efficacy of sodium glucose cotransporter 2 inhibitors on hepatic fibrosis and steatosis in non-alcoholic fatty liver disease: an updated systematic review and meta-analysis. Sci. Rep. 2024 14 1 2122 10.1038/s41598‑024‑52603‑5 38267513
    [Google Scholar]
  112. Lin J. Huang Y. Xu B. Effect of dapagliflozin on metabolic dysfunction-associated steatohepatitis: multicentre, double blind, randomised, placebo controlled trial. BMJ 2025 389 e083735 10.1136/bmj‑2024‑083735 40467095
    [Google Scholar]
  113. Makri E.S. Xanthopoulos K. Pettas S. Limited preventive effects of empagliflozin against metabolic dysfunction-associated steatotic liver disease in a mouse model of fast food diet. Hormones (Athens) 2025 24 2 419 431 10.1007/s42000‑024‑00621‑3 39699846
    [Google Scholar]
  114. Makri E.S. Makri E. Goulas A. Xanthopoulos K. Polyzos S.A. Animal studies of sodium-glucose co-transporter 2 inhibitors in nonalcoholic fatty liver disease. Ann. Gastroenterol. 2024 37 3 280 290 10.20524/aog.2024.0884 38779641
    [Google Scholar]
  115. Li C. Liang S. Gao L. Liu H. Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: A real-world systematic review and meta-analysis. PLoS One 2021 16 2 e0244689 10.1371/journal.pone.0244689 33606705
    [Google Scholar]
  116. Geng L. Sun B. Chen Y. A meta‐analysis of randomized controlled studies examining the effects of sodium‐glucose co‐transporter‐2 inhibitors on peripheral artery disease and risk of amputations. Diabetes Obes. Metab. 2024 26 11 5376 5389 10.1111/dom.15901 39267269
    [Google Scholar]
  117. Huang C.Y. Lee J.K. Sodium‐glucose co‐transporter‐2 inhibitors and major adverse limb events: A trial‐level meta‐analysis including 51 713 individuals. Diabetes Obes. Metab. 2020 22 12 2348 2355 10.1111/dom.14159 32744411
    [Google Scholar]
  118. Polyzos S.A. Mantzoros C.S. Adiponectin as a target for the treatment of nonalcoholic steatohepatitis with thiazolidinediones: A systematic review. Metabolism 2016 65 9 1297 1306 10.1016/j.metabol.2016.05.013 27506737
    [Google Scholar]
  119. Sanyal A.J. Chalasani N. Kowdley K.V. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N. Engl. J. Med. 2010 362 18 1675 1685 10.1056/NEJMoa0907929 20427778
    [Google Scholar]
  120. Musso G. Cassader M. Paschetta E. Gambino R. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis. JAMA Intern. Med. 2017 177 5 633 640 10.1001/jamainternmed.2016.9607 28241279
    [Google Scholar]
  121. Majzoub A.M. Nayfeh T. Barnard A. Systematic review with network meta‐analysis: Comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH. Aliment. Pharmacol. Ther. 2021 54 7 880 889 10.1111/apt.16583 34435378
    [Google Scholar]
  122. Dormandy J.A. Betteridge D.J. Schernthaner G. Pirags V. Norgren L. Impact of peripheral arterial disease in patients with diabetes—Results from PROactive (PROactive 11). Atherosclerosis 2009 202 1 272 281 10.1016/j.atherosclerosis.2008.03.002 18538774
    [Google Scholar]
  123. Christoph M. Herold J. Berg-Holldack A. Effects of the peroxisome proliferator-activated receptor-γ agonist pioglitazone on peripheral vessel function and clinical parameters in nondiabetic patients: A double-center, randomized controlled pilot trial. Cardiology 2015 131 3 165 171 10.1159/000376570 25967848
    [Google Scholar]
  124. Polyzos S.A. Kountouras J. Vitamin E in metabolic dysfunction‐associated steatotic liver disease. J. Gastroenterol. Hepatol. 2025 40 2 551 552 10.1111/jgh.16821 39631435
    [Google Scholar]
  125. Wang M.Y. Prabahar K. Găman M.A. Zhang J.L. Vitamin E supplementation in the treatment on nonalcoholic fatty liver disease (NAFLD): Evidence from an umbrella review of meta‐analysis on randomized controlled trials. J. Dig. Dis. 2023 24 6-7 380 389 10.1111/1751‑2980.13210 37503812
    [Google Scholar]
  126. Liu Q. Wu X. Wang Y. Wang X. Zhao F. Shi J. Association of dietary vitamin E intake with peripheral arterial disease: A retrospective cross-sectional study. PLoS One 2025 20 3 e0320356 10.1371/journal.pone.0320356 40127095
    [Google Scholar]
  127. Naqvi A.Z. Davis R.B. Mukamal K.J. Nutrient intake and peripheral artery disease in adults: Key considerations in cross-sectional studies. Clin. Nutr. 2014 33 3 443 447 10.1016/j.clnu.2013.06.011 23920500
    [Google Scholar]
  128. Alshiek J.A. Dayan L. Asleh R. Blum S. Levy A.P. Jacob G. Anti-oxidative treatment with vitamin E improves peripheral vascular function in patients with diabetes mellitus and Haptoglobin 2-2 genotype: A double-blinded cross-over study. Diabetes Res. Clin. Pract. 2017 131 200 207 10.1016/j.diabres.2017.06.026 28759833
    [Google Scholar]
  129. Törnwall M.E. Virtamo J. Haukka J.K. Effect of alpha-tocopherol (vitamin E) and beta-carotene supplementation on the incidence of intermittent claudication in male smokers. Arterioscler. Thromb. Vasc. Biol. 1997 17 12 3475 3480 10.1161/01.ATV.17.12.3475 9437195
    [Google Scholar]
  130. Törnwall M.E. Virtamo J. Haukka J.K. Aro A. Albanes D. Huttunen J.K. The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial. Atherosclerosis 1999 147 1 193 197 10.1016/S0021‑9150(99)00176‑8 10525141
    [Google Scholar]
  131. Boutari C. Pappas P.D. Anastasilakis D. Mantzoros C.S. Statins’ efficacy in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Clin. Nutr. 2022 41 10 2195 2206 10.1016/j.clnu.2022.08.001 36081293
    [Google Scholar]
  132. Fatima K. Moeed A. Waqar E. Efficacy of statins in treatment and development of non-alcoholic fatty liver disease and steatohepatitis: A systematic review and meta-analysis. Clin. Res. Hepatol. Gastroenterol. 2022 46 4 101816 10.1016/j.clinre.2021.101816 34607067
    [Google Scholar]
  133. Zhou X.D. Kim S.U. Yip T.C.F. Long-term liver-related outcomes and liver stiffness progression of statin usage in steatotic liver disease. Gut 2024 73 11 1883 1892 10.1136/gutjnl‑2024‑333074 39089860
    [Google Scholar]
  134. Zhang J. Fu S. Liu D. Wang Y. Tan Y. Statin can reduce the risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis. Eur. J. Gastroenterol. Hepatol. 2023 35 4 353 358 10.1097/MEG.0000000000002517 36719824
    [Google Scholar]
  135. Athyros V.G. Tziomalos K. Gossios T.D. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet 2010 376 9756 1916 1922 10.1016/S0140‑6736(10)61272‑X 21109302
    [Google Scholar]
  136. Sagris M. Katsaros I. Giannopoulos S. Statins and statin intensity in peripheral artery disease. Vasa 2022 51 4 198 211 10.1024/0301‑1526/a001012 35673949
    [Google Scholar]
  137. Pastori D. Farcomeni A. Milanese A. Statins and major adverse limb events in patients with peripheral artery disease: A systematic review and meta-analysis. Thromb. Haemost. 2020 120 5 866 875 10.1055/s‑0040‑1709711 32369857
    [Google Scholar]
  138. Simon T.G. Wilechansky R.M. Stoyanova S. Aspirin for metabolic dysfunction–associated steatotic liver disease without cirrhosis. JAMA 2024 331 11 920 929 10.1001/jama.2024.1215 38502074
    [Google Scholar]
  139. Simon T.G. Henson J. Osganian S. Daily aspirin use associated with reduced risk for fibrosis progression in patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 2019 17 13 2776 2784 10.1016/j.cgh.2019.04.061 31077838
    [Google Scholar]
  140. Thongtan T. Deb A. Vutthikraivit W. Antiplatelet therapy associated with lower prevalence of advanced liver fibrosis in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Indian J. Gastroenterol. 2022 41 2 119 126 10.1007/s12664‑021‑01230‑3 35318571
    [Google Scholar]
  141. Zeng R.W. Yong J.N. Tan D.J.H. Meta‐analysis: Chemoprevention of hepatocellular carcinoma with statins, aspirin and metformin. Aliment. Pharmacol. Ther. 2023 57 6 600 609 10.1111/apt.17371 36625733
    [Google Scholar]
  142. Xiao S. Liu Y. Fu X. Chen T. Xie W. Modifiable risk factors for hepatocellular carcinoma in patients with metabolic dysfunction-associated steatotic liver disease: A meta-analysis. Am. J. Med. 2024 137 11 1072 1081 10.1016/j.amjmed.2024.06.031 39047929
    [Google Scholar]
  143. Willems L.H. Maas D.P.M.S.M. Kramers K. Antithrombotic therapy for symptomatic peripheral arterial disease: A systematic review and network meta-analysis. Drugs 2022 82 12 1287 1302 10.1007/s40265‑022‑01756‑6 35997941
    [Google Scholar]
  144. Odat R.M. Ahmed M. Alshwayyat S. Aspirin plus clopidogrel versus cilostazol -based triple antiplatelet therapy in patients with ischemic heart disease undergoing PCI: A systematic review and meta-analysis of randomized controlled trials. BMC Pharmacol. Toxicol. 2025 26 1 36 10.1186/s40360‑025‑00870‑x 39980074
    [Google Scholar]
  145. El-Deen R.M. Heeba G.H. Abdel-latif R.G. Khalifa M.M.A. Comparative effectiveness of phosphodiesterase 3, 4, and 5 inhibitors in amelioration of high‐fat diet‐induced nonalcoholic fatty liver in rats. Fundam. Clin. Pharmacol. 2020 34 3 353 364 10.1111/fcp.12530 31885103
    [Google Scholar]
  146. Min T. Qiu S. Bai Y. Cao H. Guo J. Su Z. Cilostazol attenuates hepatic steatosis and intestinal disorders in nonalcoholic fatty liver disease. Int. J. Mol. Sci. 2024 25 11 6280 10.3390/ijms25116280 38892467
    [Google Scholar]
  147. Shao T. Chung R.T. Ironing out MAFLD: Therapeutic targeting of liver ferroptosis. Cell Metab. 2024 36 10 2167 2169 10.1016/j.cmet.2024.09.005 39357507
    [Google Scholar]
  148. Sui Y. Geng X. Wang Z. Zhang J. Yang Y. Meng Z. Targeting the regulation of iron homeostasis as a potential therapeutic strategy for nonalcoholic fatty liver disease. Metabolism 2024 157 155953 10.1016/j.metabol.2024.155953 38885833
    [Google Scholar]
  149. Birla S. Angural A. Madathumchalil A. Redefining the polypill: Pros and cons in cardiovascular precision medicine. Front. Pharmacol. 2023 14 1268119 10.3389/fphar.2023.1268119 37799963
    [Google Scholar]
  150. Ramandi A. George J. Merat S. Polypill protects MAFLD patients from cardiovascular events and mortality: a prospective trial. Hepatol. Int. 2023 17 4 882 888 10.1007/s12072‑023‑10542‑9 37227560
    [Google Scholar]
  151. Marzal D. Rodríguez Padial L. Arnáiz J.A. Use of the cardiovascular polypill 40mg in secondary cardiovascular prevention. Clin. Investig. Arterioscler. 2018 30 5 240 247 30017176
    [Google Scholar]
  152. Romeo S. Sanyal A. Valenti L. Leveraging human genetics to identify potential new treatments for fatty liver disease. Cell Metab. 2020 31 1 35 45 10.1016/j.cmet.2019.12.002 31914377
    [Google Scholar]
  153. Goldberg A.C. Novel therapies and new targets of treatment for familial hypercholesterolemia. J. Clin. Lipidol. 2010 4 5 350 356 10.1016/j.jacl.2010.08.015 21122677
    [Google Scholar]
  154. Cuchel M. Bloedon L.T. Szapary P.O. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N. Engl. J. Med. 2007 356 2 148 156 10.1056/NEJMoa061189 17215532
    [Google Scholar]
  155. Byrne C.D. Targher G. NAFLD: A multisystem disease. J. Hepatol. 2015 62 1 S47 S64 (Suppl.) 10.1016/j.jhep.2014.12.012 25920090
    [Google Scholar]
/content/journals/cvp/10.2174/0115701611414052251127074106
Loading
Metabolic Dysfunction-Associated Steatotic Liver Disease and Peripheral Arterial Disease: Associations and Treatment Considerations
Bentham Science Publishers ; https://doi.org/10.2174/0115701611414052251127074106
/content/journals/cvp/10.2174/0115701611414052251127074106
/content/journals/cvp/10.2174/0115701611414052251127074106
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: metabolic dysfunction-associated steatotic liver disease ; therapy ; nonalcoholic steatohepatitis ; metabolic dysfunction-associated steatohepatitis ; lower extremity artery disease ; nonalcoholic fatty liver disease ; Atherosclerosis ; peripheral arterial disease

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test