Advertisement

Subclinical and clinical atherosclerosis in non-alcoholic fatty liver disease is associated with the presence of hypertension

  • Filippo Cattazzo
    Correspondence
    Corresponding author. University and Azienda Ospedaliera Universitaria Integrata of Verona, Department of Medicine, General Medicine, Hypertension Unit & Liver Unit, Hospital “Policlinico G.B. Rossi”, P.le L.A. Scuro 10, 37134 Verona, Italy.
    Affiliations
    General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
    Search for articles by this author
  • Rosa Lombardi
    Affiliations
    Unit of Internal Medicine and Metabolic Disease, Ca’ Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
    Search for articles by this author
  • Anna Mantovani
    Affiliations
    General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
    Search for articles by this author
  • Michele Bevilacqua
    Affiliations
    General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
    Search for articles by this author
  • Mirko Zoncapè
    Affiliations
    General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
    Search for articles by this author
  • Laura Iogna Prat
    Affiliations
    UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
    Search for articles by this author
  • Davide Roccarina
    Affiliations
    UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
    Search for articles by this author
  • Leonardo Fortuna
    Affiliations
    General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
    Search for articles by this author
  • Annalisa Cespiati
    Affiliations
    Unit of Internal Medicine and Metabolic Disease, Ca’ Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
    Search for articles by this author
  • David Sacerdoti
    Affiliations
    General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
    Search for articles by this author
  • Anna L. Fracanzani
    Affiliations
    Unit of Internal Medicine and Metabolic Disease, Ca’ Granda IRCCS Foundation, Policlinico Hospital, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
    Search for articles by this author
  • Emmanouil Tsochatzis
    Affiliations
    UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Cristiano Fava
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Andrea Dalbeni
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    General Medicine C, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • Overt atherosclerosis was significantly present only in NAFLD+HT patients, but not in patients presenting with isolated NAFLD.
      • The impact of NAFLD on vascular structure and function could depend on the coexistence of other major cardiovascular risk factors.
      • This would imply a change in the management of the cardiovascular risk in NAFLD patients.

      Abstract

      Background and aims

      Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular (CV) risk. However, it is unclear whether NAFLD contributes independently to the development of CV disease. Our study aimed at assessing the differences in several indices of atherosclerosis, arterial stiffness and cardiac morphology among patients with isolated NAFLD, isolated hypertension (HT) or a combination of the two conditions.

      Methods and results

      A total of 169 participants (mean age = 50.4 ± 10.2 yrs; males = 73.6%) were divided according to the presence of NAFLD and HT into three groups: only NAFLD (55 patients), only HT (49 patients), and NAFLD + HT (65 patients). Exclusion criteria were a BMI≥35 kg/m2 and a diagnosis of diabetes mellitus. Carotid ultrasonography was performed to measure markers of atherosclerosis and arterial stiffness. Cardiac remodeling was analyzed using echocardiography. The prevalence of subclinical and overt atherosclerosis was significantly higher in the NAFLD + HT patients as compared to the other two groups (atherosclerotic plaques: 43.1%, 10.9%, and 22.4% (p < 0.001) in NAFLD + HT, NAFLD, and HT groups, respectively). No differences were found among indices of arterial stiffening and cardiac remodeling across the three groups. In multivariate regression analysis, the coexistence of NAFLD and HT was an independent risk factor for overt atherosclerosis (OR = 4.88, CI 95% 1.14–20.93), while no association was found when either NAFLD or HT was considered alone.

      Conclusion

      Overt atherosclerosis was significantly present only in NAFLD + HT patients, but not in patients with isolated NAFLD. This implies that the impact of NAFLD on vascular structure and function could depend on the coexistence of other major CV risk factors, such as HT.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Nutrition, Metabolism and Cardiovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Serfaty L.
        • Lemoine M.
        Definition and natural history of metabolic steatosis: clinical aspects of NAFLD, NASH and cirrhosis.
        Diab Metab. 2008; 34 ([Internet]): 634-637https://doi.org/10.1016/S1262-3636(08)74597-X
        • Younossi Z.M.
        • Koenig A.B.
        • Abdelatif D.
        • Fazel Y.
        • Henry L.
        • Wymer M.
        Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes.
        Hepatology. 2016; 64: 73-84
        • Ekstedt M.
        • Hagström H.
        • Nasr P.
        • Fredrikson M.
        • Stål P.
        • Kechagias S.
        • 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: 1547-1554
        • Fracanzani A.L.
        • Tiraboschi S.
        • Pisano G.
        • Consonni D.
        • Baragetti A.
        • Bertelli C.
        • et al.
        Progression of carotid vascular damage and cardiovascular events in non-alcoholic fatty liver disease patients compared to the general population during 10 years of follow-up.
        Atherosclerosis. 2016; 246 ([Internet]): 208-213https://doi.org/10.1016/j.atherosclerosis.2016.01.016
        • Oni E.T.
        • Agatston A.S.
        • Blaha M.J.
        • Fialkow J.
        • Cury R.
        • Sposito A.
        • et al.
        A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; Should we care?.
        Atherosclerosis. 2013; 230 ([Internet]): 258-267https://doi.org/10.1016/j.atherosclerosis.2013.07.052
        • Targher G.
        • Bertolini L.
        • Padovani R.
        • Rodella S.
        • Zoppini G.
        • Zenari L.
        • et al.
        Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease.
        Diabetes Care. 2006; 29: 1325-1330
        • Wong V.W.S.
        • Wong G.L.H.
        • Yip G.W.K.
        • Lo A.O.S.
        • Limquiaco J.
        • Chu W.C.W.
        • et al.
        Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease.
        Gut. 2011; 60: 1721-1727
        • Sinn D.H.
        • Kang D.
        • Chang Y.
        • Ryu S.
        • Gu S.
        • Kim H.
        • et al.
        Non-alcoholic fatty liver disease and progression of coronary artery calcium score: a retrospective cohort study.
        Gut. 2017; 66: 323-329
        • Salvi P.
        • Ruffini R.
        • Agnoletti D.
        • Magnani E.
        • Pagliarani G.
        • Comandini G.
        • et al.
        Increased arterial stiffness in nonalcoholic fatty liver disease: the Cardio-GOOSE study.
        J Hypertens. 2010; 28: 1699-1707
        • van Sloten T.T.
        • Schram M.T.
        • van den Hurk K.
        • Dekker J.M.
        • Nijpels G.
        • Henry R.M.A.
        • et al.
        Local stiffness of the carotid and femoral artery is associated with incident cardiovascular events and all-cause mortality: the hoorn study.
        J Am Coll Cardiol. 2014; 63: 1739-1747
        • Petta S.
        • Argano C.
        • Colomba D.
        • Cammà C.
        • di Marco V.
        • Cabibi D.
        • et al.
        Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: association with the severity of liver disease.
        J Hepatol. 2015; 62 ([Internet]): 928-933https://doi.org/10.1016/j.jhep.2014.11.030
        • Fracanzani A.L.
        • Pisano G.
        • Consonni D.
        • Tiraboschi S.
        • Baragetti A.
        • Bertelli C.
        • et al.
        Epicardial Adipose Tissue (EAT) thickness is associated with cardiovascular and liver damage in nonalcoholic fatty liver disease.
        PLoS One. 2016; 11: 1-19
        • el Azeem H.A.
        • Khalek E.S.A.
        • El-Akabawy H.
        • Naeim H.
        • Khalik H.A.
        • Alfifi A.A.
        Association between nonalcoholic fatty liver disease and the incidence of cardiovascular and renal events.
        J Saudi Heart Assoc. 2013; 25 ([Internet]): 239-246https://doi.org/10.1016/jsha.2013.07.004
        • Marchesini G.
        • Bugianesi E.
        • Forlani G.
        • Cerrelli F.
        • Lenzi M.
        • Manini R.
        • et al.
        Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome.
        Hepatology. 2003; 37: 917-923
        • Ratziu V.
        • Bellentani S.
        • Cortez-Pintoc H.
        • Dayd C.
        • Marchesini G.
        A position statement on NAFLD/NASH based on the EASL 2009 special conference.
        J Hepatol. 2010; 53 ([Internet]): 372-384https://doi.org/10.1016/j.jhep.2010.04.008
        • Petta S.
        • Cammà C.
        • Cabibi D.
        • di Marco V.
        • Craxì A.
        Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease.
        Aliment Pharmacol Therapeut. 2011; 34: 757-766
        • Targher G.
        • Bertolini L.
        • Rodella S.
        • Zoppini G.
        • Scala L.
        • Zenari L.
        • et al.
        Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease.
        Clin Endocrinol. 2006; 64: 679-683
        • Tripodi A.
        • Fracanzani A.L.
        • Primignani M.
        • Chantarangkul V.
        • Clerici M.
        • Mannucci P.M.
        • et al.
        Procoagulant imbalance in patients with non-alcoholic fatty liver disease.
        J Hepatol. 2014; 61 ([Internet]): 148-154https://doi.org/10.1016/j.jhep.2014.03.013
        • Seo B.
        • Roh J.
        • Lee J.
        • Lee H.
        • Min Kim Y.
        • Yoon Y.
        • et al.
        Association between nonalcoholic fatty liver disease and cardiovascular disease revealed after comprehensive control of metabolic risk factors a nationwide population-based study in Korea.
        Eur J Gastroenterol Hepatol. 2021;
        • Liu Z.
        • Wei R.
        • Li Y.
        Coronary heart disease is associated with nonalcoholic fatty liver disease in patients without hypertension and diabetes.
        Medicine. 2020; 99e20898
        • Targher G.
        • Mantovani A.
        • Grander C.
        • Foco L.
        • Motta B.
        • Byrne C.D.
        • et al.
        Association between non-alcoholic fatty liver disease and impaired cardiac sympathetic/parasympathetic balance in subjects with and without type 2 diabetes—the Cooperative Health Research in South Tyrol (CHRIS)-NAFLD sub-study.
        Nutr Metabol Cardiovasc Dis. 2021; 31 ([Internet]): 3464-3473https://doi.org/10.1016/j.numecd.2021.08.037
        • Shahab O.
        • Biswas R.
        • Paik J.
        • Bush H.
        • Golabi P.
        • Younossi Z.M.
        Among patients with NAFLD, treatment of dyslipidemia does not reduce cardiovascular mortality.
        Hepatol Commun. 2018; 2: 1227-1234
        • Williams B.
        • Mancia G.
        • Wilko S.
        • Agabiti Rosei E.
        • Azizi M.
        • Burnier M.
        • et al.
        2018 ESC/ESHGuidelines for themanagement ofarterial hypertension: the task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the European society of cardiology (ESC). Vol. 39.
        Eur Heart J. 2018; : 3021-3104
        • Saadeh S.
        • Younossi Z.M.
        • Remer E.M.
        • Gramlich T.
        • Ong J.P.
        • Hurley M.
        • et al.
        The utility of radiological imaging in nonalcoholic fatty liver disease.
        Gastroenterology. 2002; 123: 745-750
        • Bertoli S.
        • Leone A.
        • Vignati L.
        • Spadafranca A.
        • Bedogni G.
        • Vanzulli A.
        • et al.
        Metabolic correlates of subcutaneous and visceral abdominal fat measured by ultrasonography: a comparison with waist circumference.
        Nutr J. 2016; 15 ([Internet]): 1-8https://doi.org/10.1186/s12937-015-0120-2
        • Castera L.
        • Forns X.
        • Alberti A.
        Non-invasive evaluation of liver fibrosis using transient elastography.
        J Hepatol. 2008; 48: 835-847
        • Shah A.G.
        • Lydecker A.
        • Murray K.
        • Tetri B.N.
        • Contos M.J.
        • Sanyal A.J.
        • et al.
        Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease.
        Clin Gastroenterol Hepatol. 2009; 7: 1104-1112
        • Giannarelli C.
        • Bianchini E.
        • Bruno R.M.
        • Magagna A.
        • Landini L.
        • Faita F.
        • et al.
        Local carotid stiffness and intima-media thickness assessment by a novel ultrasound-based system in essential hypertension.
        Atherosclerosis. 2012; 223 ([Internet]): 372-377https://doi.org/10.1016/j.atherosclerosis.2012.05.027
        • Iacobellis G.
        • Ribaudo M.C.
        • Assael F.
        • Vecci E.
        • Tiberti C.
        • Zappaterreno A.
        • et al.
        Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk.
        J Clin Endocrinol Metab. 2003; 88: 5163-5168
        • Iacobellis G.
        • Willens H.J.
        • Barbaro G.
        • Sharma A.M.
        Threshold values of high-risk echocardiographic epicardial fat thickness.
        Obesity. 2008; 16: 887-892
        • Redfield M.
        • Jacobsen S.
        • Burnett J.
        Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic.
        JAMA. 2003; 289: 194-202
        • de Simone G.
        • Daniels S.R.
        • Kimball T.R.
        • Roman M.J.
        • Romano C.
        • Chinali M.
        • et al.
        Evaluation of concentric left ventricular geometry in humans: evidence for age-related systematic underestimation.
        Hypertension. 2005; 45: 64-68
        • Lang R.M.
        • Badano L.P.
        • Victor M.A.
        • Afilalo J.
        • Armstrong A.
        • Ernande L.
        • et al.
        Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
        J Am Soc Echocardiogr. 2015; 28 ([Internet])https://doi.org/10.1016/j.echo.2014.10.003
        • Lewis-Beck M.S.
        • Bryman A.
        • Futing Liao T.
        Stepwise regression.
        in: The SAGE encyclopedia of social science research methods. Thousand O. Sage Publications, Inc., 2004 (1-0)
        • Fallo F.
        • Pozza A.D.
        • Sonino N.
        • Federspil G.
        • Ermani M.
        • Baroselli S.
        • et al.
        Nonalcoholic fatty liver disease, adiponectin and insulin resistance in dipper and nondipper essential hypertensive patients.
        J Hypertens. 2008; 26: 2191-2197
        • Eslam M.
        • Newsome P.N.
        • Sarin S.K.
        • Anstee Q.M.
        • 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 ([Internet]): 202-209https://doi.org/10.1016/j.jhep.2020.03.039
        • Wu S.
        • Wu F.
        • Ding Y.
        • Hou J.
        • Bi J.
        • Zhang Z.
        Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: a systematic review and meta-analysis.
        Sci Rep. 2016; 6 ([Internet]): 1-14https://doi.org/10.1038/srep33386
        • Ciardullo S.
        • Grassi G.
        • Mancia G.
        • Perseghin G.
        Nonalcoholic fatty liver disease and risk of incident hypertension.
        Eur J Gastroenterol Hepatol. 2021; ([Publish Ah(November)])
        • Singh S.
        • Allen A.M.
        • Wang Z.
        • Prokop L.J.
        • Murad M.H.
        • Loomba R.
        Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies.
        Clin Gastroenterol Hepatol. 2015; 13 ([Internet])https://doi.org/10.1016/j.cgh.2014.04.014
        • Tsuneto A.
        • Hida A.
        • Sera N.
        • Imaizumi M.
        • Ichimaru S.
        • Nakashima E.
        • et al.
        Fatty liver incidence and predictive variables.
        Hypertension Res. 2010; 33 ([Internet]): 638-643https://doi.org/10.1038/hr.2010.45
        • Zhang T.
        • Zhang C.
        • Zhang Y.
        • Tang F.
        • Li H.
        • Zhang Q.
        • et al.
        Metabolic syndrome and its components as predictors of nonalcoholic fatty liver disease in a northern urban Han Chinese population: a prospective cohort study.
        Atherosclerosis. 2015; 240 ([Internet]): 144-148https://doi.org/10.1016/j.atherosclerosis.2015.02.049
        • Aneni E.C.
        • Oni E.T.
        • Martin S.S.
        • Blaha M.J.
        • Agatston A.S.
        • Feldman T.
        • et al.
        Blood pressure is associated with the presence and severity of nonalcoholic fatty liver disease across the spectrum of cardiometabolic risk.
        J Hypertens. 2015; 33: 1207-1214
        • Petta S.
        • di Marco V.
        • Pipitone R.M.
        • Grimaudo S.
        • Buscemi C.
        • Craxì A.
        • et al.
        Prevalence and severity of nonalcoholic fatty liver disease by transient elastography: genetic and metabolic risk factors in a general population.
        Liver Int. 2018; 38: 2060-2068
        • Han J.
        • Wang Y.
        • Yuan Z.
        • Liu L.
        • Zhao M.
        • Guan Q.
        • et al.
        Nonalcoholic fatty liver disease represents a greater metabolic burden in patients with atherosclerosis: a cross-sectional study.
        Medicine. 2019; 98
        • Younossi Z.M.
        • Stepanova M.
        • Younossi Y.
        • Golabi P.
        • Mishra A.
        • Rafiq N.
        • et al.
        Epidemiology of chronic liver diseases in the USA in the past three decades.
        Gut. 2020; 69: 564-568
        • Ma J.
        • Hwang S.J.
        • Pedley A.
        • Massaro J.M.
        • Hoffmann U.
        • Chung R.T.
        • et al.
        Bi-directional analysis between fatty liver and cardiovascular disease risk factors.
        J Hepatol. 2017; 66 ([Internet]): 390-397https://doi.org/10.1016/j.jhep.2016.09.022
        • Oni E.
        • Budoff M.J.
        • Zeb I.
        • Li D.
        • Veledar E.
        • Polak J.F.
        • et al.
        Nonalcoholic fatty liver disease is associated with arterial distensibility and carotid intima-media thickness: (from the multi-ethnic study of atherosclerosis).
        Am J Cardiol. 2019; 124 ([Internet]): 534-538https://doi.org/10.1016/j.amjcard.2019.05.028
        • Taharboucht S.
        • Guermaz R.
        • Brouri M.
        • Chibane A.
        Subclinical atherosclerosis and arterial stiffness in nonalcoholic fatty liver disease: a case-control study in Algerian population.
        JMV-J Med Vascul. 2021; 46 ([Internet]): 129-138https://doi.org/10.1016/j.jdmv.2021.03.008
        • Zheng J.
        • Zhou Y.
        • Zhang K.
        • Qi Y.
        • An S.
        • Wang S.
        • et al.
        Association between nonalcoholic fatty liver disease and subclinical atherosclerosis: a cross-sectional study on population over 40 years old.
        BMC Cardiovasc Disord. 2018; 18: 1-7
        • Ozturk K.
        • Uygun A.
        • Guler A.K.
        • Demirci H.
        • Ozdemir C.
        • Cakir M.
        • et al.
        Nonalcoholic fatty liver disease is an independent risk factor for atherosclerosis in young adult men.
        Atherosclerosis. 2015; 240: 380-386
        • Yu X.
        • Chen C.
        • Guo Y.
        • Tong Y.
        • Zhao Y.
        • Wu L.
        • et al.
        High NAFLD fibrosis score in non-alcoholic fatty liver disease as a predictor of carotid plaque development: a retrospective cohort study based on regular health check-up data in China.
        Ann Med. 2021; 53 ([Internet]): 1621-1631https://doi.org/10.1080/07853890.2021.1974081
        • Perticone M.
        • Cimellaro A.
        • Maio R.
        • Caroleo B.
        • Sciacqua A.
        • Sesti G.
        • et al.
        Additive effect of non-alcoholic fatty liver disease on metabolic syndrome-related endothelial dysfunction in hypertensive patients.
        Int J Mol Sci. 2016; 17
        • Styczyński G.
        • Kalinowski P.
        • Michałowski Ł.
        • Paluszkiewicz R.
        • Ziarkiewicz-Wróblewska B.
        • Zieniewicz K.
        • et al.
        No association between aortic stiffness and liver steatosis in morbidly obese patients.
        Atherosclerosis. 2019; 287 ([Internet]): 165-170https://doi.org/10.1016/j.atherosclerosis.2019.04.206
        • Catena C.
        • Bernardi S.
        • Sabato N.
        • Grillo A.
        • Ermani M.
        • Sechi L.A.
        • et al.
        Ambulatory arterial stiffness indices and non-alcoholic fatty liver disease in essential hypertension.
        Nutr Metabol Cardiovasc Dis. 2013; 23 ([Internet]): 389-393https://doi.org/10.1016/j.numecd.2012.05.007
        • Arai T.
        • Atsukawa M.
        • Tsubota A.
        • Kato K.
        • Abe H.
        • Ono H.
        • et al.
        Liver fibrosis is associated with carotid atherosclerosis in patients with liver biopsy-proven nonalcoholic fatty liver disease.
        Sci Rep. 2021; 11 ([Internet]): 1-10https://doi.org/10.1038/s41598-021-95581-8
        • Baratta F.
        • Pastori D.
        • Angelico F.
        • Balla A.
        • Paganini A.M.
        • Cocomello N.
        • et al.
        Nonalcoholic fatty liver disease and fibrosis associated with increased risk of cardiovascular events in a prospective study.
        Clin Gastroenterol Hepatol. 2020; 18 ([Internet])https://doi.org/10.1016/j.cgh.2019.12.026
        • Kasper P.
        • Martin A.
        • Lang S.
        • Kütting F.
        • Goeser T.
        • Demir M.
        • et al.
        NAFLD and cardiovascular diseases: a clinical review.
        Clin Res Cardiol. 2021; 110 ([Internet]): 921-937https://doi.org/10.1007/s00392-020-01709-7
        • Fotbolcu H.
        • Yakar T.
        • Duman D.
        • Karaahmet T.
        • Tigen K.
        • Cevik C.
        • et al.
        Impairment of the left ventricular systolic and diastolic function in patients with non-alcoholic fatty liver disease.
        Cardiol J. 2010; 17: 457-463
        • VanWagner L.
        • Wilcox J.
        • Colangelo L.
        • Lloyd-Jones D.
        • Carr J.
        • Lima J.
        • et al.
        Association of nonalcoholic fatty liver disease with subclinical myocardial remodeling and dysfunction: a population-based study.
        Hepatology. 2015; 62: 773-783
        • Sert A.
        • Aypar E.
        • Pirgon O.
        • Yilmaz H.
        • Odabas D.
        • Tolu I.
        Left ventricular function by echocardiography, tissue Doppler imaging, and carotid intima-media thickness in obese adolescents with nonalcoholic fatty liver disease.
        Am J Cardiol. 2013; 112 ([Internet]): 436-443https://doi.org/10.1016/j.amjcard.2013.03.056
        • Meng X.
        • Wang W.
        • Zhang K.
        • Qi Y.
        • An S.
        • Wang S.
        • et al.
        Epicardial adipose tissue volume is associated with non-alcoholic fatty liver disease and cardiovascular risk factors in the general population.
        Therapeut Clin Risk Manag. 2018; 14: 1499-1506