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Non-alcoholic fatty liver disease presence and severity are associated with aortic stiffness beyond abdominal obesity: The ELSA-Brasil

  • Paulo H. Harada
    Affiliations
    Center for Clinical and Epidemiological Research, University Hospital, University of Sao Paulo, Sao Paulo, Brazil, Department of Medicine, School of Medicine University of Sao Paulo, Sao Paulo, Brazil, 2565 Prof. Lineu Prestes Avenue, Sao Paulo, SP, 05508-000, Brazil
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  • Isabela J.M. Bensenõr
    Affiliations
    Center for Clinical and Epidemiological Research, University Hospital, University of Sao Paulo, Sao Paulo, Brazil, Department of Medicine, School of Medicine University of Sao Paulo, Sao Paulo, Brazil, 2565 Prof. Lineu Prestes Avenue, Sao Paulo, SP, 05508-000, Brazil
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  • Luciano F. Drager
    Affiliations
    Hypertension Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil, 44 Dr Eneas Carvalho de Aguiar Avenue, Sao Paulo, SP, 05403-900, Brazil

    Hypertension Unit, Renal Division, University of São Paulo Medical School, São Paulo, Brazil, 255 Dr. Enéas Carvalho de Aguiar, São Paulo, SP, 01246-000, Brazil
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  • Alessandra C. Goulart
    Affiliations
    Center for Clinical and Epidemiological Research, University Hospital, University of Sao Paulo, Sao Paulo, Brazil, Department of Medicine, School of Medicine University of Sao Paulo, Sao Paulo, Brazil, 2565 Prof. Lineu Prestes Avenue, Sao Paulo, SP, 05508-000, Brazil
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  • José G. Mill
    Affiliations
    Department of Physiological Sciences, Federal University of Espírito Santo, 1468 Marechal Campos Avenue, Vitória, ES, 29042- 755, Brazil
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  • Paulo A. Lotufo
    Correspondence
    Corresponding author.
    Affiliations
    Center for Clinical and Epidemiological Research, University Hospital, University of Sao Paulo, Sao Paulo, Brazil, Department of Medicine, School of Medicine University of Sao Paulo, Sao Paulo, Brazil, 2565 Prof. Lineu Prestes Avenue, Sao Paulo, SP, 05508-000, Brazil
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      Highlights

      • There is a cardiovascular risk (CV) gap beyond traditional risk factors.
      • Non-alcoholic fatty liver disease (NAFLD) is independently related to CV risk.
      • NAFLD association with pulse wave velocity (PWV) is controversial.
      • NAFLD is associated with PWV across race/ethnic diverse ELSA-Brasil population.
      • The worldwide CVD burden of disease related to NAFLD is potentially relevant.

      Abstract

      Background and aims

      It is uncertain whether non-alcoholic fatty liver disease (NAFLD) is associated with aortic stiffness in a racial/ethnically diverse and admixed society. We addressed whether NAFLD presence and severity were associated with carotid-femoral pulse wave velocity (cf-PWV) in individuals free of cardiovascular disease.

      Methods

      In 7196 individuals free of cardiovascular disease at the baseline Brazilian longitudinal study of adult health, we classified NAFLD presence and severity (mild, moderate and severe) by ultrasound hepatic attenuation. We measured cf-PWV using a non-invasive validated device (Complior SP, Artech Medicale France). We compared cf-PWV of NAFLD individuals to those without by analysis of covariance adjusted for demographics, life style, waist circumference, and arterial pressure. We also analyzed the cf-PWV trend from no-NAFLD to severe NAFLD.

      Results

      In unadjusted analysis, from no-NAFLD to severe NAFLD, there were slightly older individuals, lower frequency of smokers, more prevalent diabetes and hypertension. In adjusted analysis, there was slightly higher cf-PWV (m/s) (95%CI) in NAFLD vs. no-NAFLD, respectively 9.32 (9.22, 9.41) and 9.24 (9.15, 9.33) (p = 0.037). Across NAFLD severity spectrum, adjusted cf-PWV increased from 9.24 (9.15, 9.33) in no-NAFLD to 9.69 (9.46, 9.93) in severe NAFLD (p for trend association = 0.001). In sensitivity analysis, diabetes adjustment nullified the association of binary NAFLD with cf-PWV, but not that of increasingly severe NAFLD.

      Conclusions

      In racial/ethnically diverse individuals free of cardiovascular disease, NAFLD is associated with aortic stiffness beyond abdominal obesity. The specific NAFLD impact on CVD worldwide is potentially relevant.

      Graphical abstract

      Keywords

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      References

        • Lozano R.
        • Naghavi M.
        • Foreman K.
        • Lim S.
        • Shibuya K.
        • et al.
        Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.
        Lancet. 2012; 380: 2095-2128https://doi.org/10.1016/S0140-6736(12)61728-0
        • Khot U.N.
        • Khot M.B.
        • Bajzer C.T.
        • Sapp S.K.
        • Ohman E.M.
        • et al.
        Prevalence of conventional risk factors in patients with coronary heart disease.
        J. Am. Med. Assoc. 2003; 290: 898-904https://doi.org/10.1001/jama.290.7.898
        • Lazo M.
        • Clark J.M.
        The epidemiology of nonalcoholic fatty liver disease: a global perspective.
        Semin. Liver Dis. 2008; 28: 339-350https://doi.org/10.1055/s-0028-1091978
        • Ong J.P.
        • Pitts A.
        • Younossi Z.M.
        Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease.
        J. Hepatol. 2008; 49: 608-612https://doi.org/10.1016/j.jhep.2008.06.018
        • Mantovani A.
        • Byrne C.D.
        • Bonora E.
        • Targher G.
        Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis.
        Diabetes Care. 2018; 41: 372-382https://doi.org/10.2337/dc17-1902
        • Yki-Jarvinen H.
        Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome.
        Lancet Diabetes Endocrinol. 2014; 2: 901-910https://doi.org/10.1016/S2213-8587(14)70032-4
        • Oni E.T.
        • Agatston A.S.
        • Blaha M.J.
        • Fialkow J.
        • Cury R.
        • et al.
        A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care?.
        Atherosclerosis. 2013; 230: 258-267https://doi.org/10.1016/j.atherosclerosis.2013.07.052
        • Zeb I.
        • Li D.
        • Budoff M.J.
        • Katz R.
        • Lloyd-Jones D.
        • et al.
        Nonalcoholic fatty liver disease and incident cardiac events: the multi-ethnic study of atherosclerosis.
        J. Am. Coll. Cardiol. 2016; 67: 1965-1966https://doi.org/10.1016/j.jacc.2016.01.070
        • Hamaguchi M.
        • Kojima T.
        • Takeda N.
        • Nagata C.
        • Takeda J.
        • et al.
        Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease.
        World J. Gastroenterol. 2007; 13: 1579-1584
        • Targher G.
        • Bertolini L.
        • Poli F.
        • Rodella S.
        • Scala L.
        • et al.
        Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients.
        Diabetes. 2005; 54: 3541-3546
        • Targher G.
        • Byrne C.D.
        • Lonardo A.
        • Zoppini G.
        • Barbui C.
        Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis.
        J. Hepatol. 2016; 65: 589-600https://doi.org/10.1016/j.jhep.2016.05.013
        • Ben-Shlomo Y.
        • Spears M.
        • Boustred C.
        • May M.
        • Anderson S.G.
        • et al.
        Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects.
        J. Am. Coll. Cardiol. 2014; 63: 636-646https://doi.org/10.1016/j.jacc.2013.09.063
        • Mitchell G.F.
        • Hwang S.J.
        • Vasan R.S.
        • Larson M.G.
        • Pencina M.J.
        • et al.
        Arterial stiffness and cardiovascular events: the Framingham heart study.
        Circulation. 2010; 121: 505-511https://doi.org/10.1161/CIRCULATIONAHA.109.886655
        • Vlachopoulos C.
        • Aznaouridis K.
        • Stefanadis C.
        Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis.
        J. Am. Coll. Cardiol. 2010; 55: 1318-1327https://doi.org/10.1016/j.jacc.2009.10.061
        • Betticher D.C.
        • Hsu Schmitz S.F.
        • Totsch M.
        • Hansen E.
        • Joss C.
        • et al.
        Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study.
        Br. J. Canc. 2006; 94: 1099-1106https://doi.org/10.1038/sj.bjc.6603075
        • Cecelja M.
        • Chowienczyk P.
        Dissociation of aortic pulse wave velocity with risk factors for cardiovascular disease other than hypertension: a systematic review.
        Hypertension. 2009; 54: 1328-1336https://doi.org/10.1161/HYPERTENSIONAHA.109.137653
        • Baldo M.P.
        • Cunha R.S.
        • Ribeiro A.L.P.
        • Lotufo P.A.
        • Chor D.
        • et al.
        Racial differences in arterial stiffness are mainly determined by blood pressure levels: results from the ELSA-Brasil study.
        J. Am. Heart Assoc. 2017; https://doi.org/10.1161/JAHA.117.005477
        • Baldo M.P.
        • Cunha R.S.
        • Molina M.
        • Chor D.
        • Griep R.H.
        • et al.
        Carotid-femoral pulse wave velocity in a healthy adult sample: the ELSA-Brasil study.
        Int. J. Cardiol. 2018; 251: 90-95https://doi.org/10.1016/j.ijcard.2017.10.075
        • Salvi P.
        • Ruffini R.
        • Agnoletti D.
        • Magnani E.
        • Pagliarani G.
        • et al.
        Increased arterial stiffness in nonalcoholic fatty liver disease: the Cardio-GOOSE study.
        J. Hypertens. 2010; 28: 1699-1707https://doi.org/10.1097/HJH.0b013e32833a7de6
        • Vlachopoulos C.
        • Manesis E.
        • Baou K.
        • Papatheodoridis G.
        • Koskinas J.
        • et al.
        Increased arterial stiffness and impaired endothelial function in nonalcoholic Fatty liver disease: a pilot study.
        Am. J. Hypertens. 2010; 23: 1183-1189https://doi.org/10.1038/ajh.2010.144
        • Ozturk K.
        • Uygun A.
        • Guler A.K.
        • Demirci H.
        • Ozdemir C.
        • et al.
        Nonalcoholic fatty liver disease is an independent risk factor for atherosclerosis in young adult men.
        Atherosclerosis. 2015; 240: 380-386https://doi.org/10.1016/j.atherosclerosis.2015.04.009
        • Long M.T.
        • Wang N.
        • Larson M.G.
        • Mitchell G.F.
        • Palmisano J.
        • et al.
        Nonalcoholic fatty liver disease and vascular function: cross-sectional analysis in the Framingham heart study.
        Arterioscler. Thromb. Vasc. Biol. 2015; 35: 1284-1291https://doi.org/10.1161/ATVBAHA.114.305200
        • Kim B.J.
        • Kim N.H.
        • Kim B.S.
        • Kang J.H.
        The association between nonalcoholic fatty liver disease, metabolic syndrome and arterial stiffness in nondiabetic, nonhypertensive individuals.
        Cardiology. 2012; 123: 54-61https://doi.org/10.1159/000341248
        • Huang Y.
        • Bi Y.
        • Xu M.
        • Ma Z.
        • Xu Y.
        • et al.
        Nonalcoholic fatty liver disease is associated with atherosclerosis in middle-aged and elderly Chinese.
        Arterioscler. Thromb. Vasc. Biol. 2012; 32: 2321-2326https://doi.org/10.1161/ATVBAHA.112.252957
        • Lee Y.J.
        • Shim J.Y.
        • Moon B.S.
        • Shin Y.H.
        • Jung D.H.
        • et al.
        The relationship between arterial stiffness and nonalcoholic fatty liver disease.
        Dig. Dis. Sci. 2012; 57: 196-203https://doi.org/10.1007/s10620-011-1819-3
        • Kim N.H.
        • Park J.
        • Kim S.H.
        • Kim Y.H.
        • Kim D.H.
        • et al.
        Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population.
        Heart. 2014; 100: 938-943https://doi.org/10.1136/heartjnl-2013-305099
        • Schmidt M.I.
        • Duncan B.B.
        • Mill J.G.
        • Lotufo P.A.
        • Chor D.
        • et al.
        Cohort profile: longitudinal study of adult health (ELSA-Brasil).
        Int. J. Epidemiol. 2015; 44: 68-75https://doi.org/10.1093/ije/dyu027
        • Bensenor I.M.
        • Griep R.H.
        • Pinto K.A.
        • Faria C.P.
        • Felisbino-Mendes M.
        • et al.
        [Routines of organization of clinical tests and interviews in the ELSA-Brasil investigation center].
        Rev. Saude Publica. 2013; 47: 37-47https://doi.org/10.1590/S0034-8910.2013047003780
        • Fedeli L.G.
        • Vidigal P.G.
        • Leite C.M.
        • Castilhos C.D.
        • Pimentel R.A.
        • et al.
        [Logistics of collection and transportation of biological samples and the organization of the central laboratory in the ELSA-Brasil].
        Rev. Saude Publica. 2013; 47: 63-71
        • Lotufo P.A.
        [Setting up the longitudinal study for adult health (ELSA-Brasil].
        Rev. Saude Publica. 2013; 47: 3-9
        • Mill J.G.
        • Pinto K.
        • Griep R.H.
        • Goulart A.
        • Foppa M.
        • et al.
        [Medical assessments and measurements in ELSA-Brasil].
        Rev. Saude Publica. 2013; 47: 54-62
        • Joy D.
        • Thava V.R.
        • Scott B.B.
        Diagnosis of fatty liver disease: is biopsy necessary?.
        Eur. J. Gastroenterol. Hepatol. 2003; 15: 539-543https://doi.org/10.1097/01.meg.0000059112.41030.2e
        • Saadeh S.
        • Younossi Z.M.
        • Remer E.M.
        • Gramlich T.
        • Ong J.P.
        • et al.
        The utility of radiological imaging in nonalcoholic fatty liver disease.
        Gastroenterology. 2002; 123: 745-750
        • Goulart A.C.
        • Oliveira I.R.
        • Alencar A.P.
        • Santos M.S.
        • Santos I.S.
        • et al.
        Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
        Sao Paulo Med. J. 2015; 133: 115-124https://doi.org/10.1590/1516-3180.2014.9150812
        • Harada P.H.
        • Bensenõr I.J.M.
        • Drager L.F.
        • Goulart A.C.
        • Mill J.G.
        • Lotufo P.A.
        Non-Alcoholic Fatty Liver Disease Association with Aortic Stiffness: Variations According to Waist Circumference and Fatty Liver Index Classification Atherosclerosis (Data in Brief) Submitted.
        2018
        • Bedogni G.
        • Bellentani S.
        • Miglioli L.
        • Masutti F.
        • Passalacqua M.
        • et al.
        The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population.
        BMC Gastroenterol. 2006; 6: 33https://doi.org/10.1186/1471-230X-6-33
        • Seppala-Lindroos A.
        • Vehkavaara S.
        • Hakkinen A.M.
        • Goto T.
        • Westerbacka J.
        • et al.
        Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men.
        J. Clin. Endocrinol. Metab. 2002; 87: 3023-3028https://doi.org/10.1210/jcem.87.7.8638
        • Harada P.H.N.
        • Demler O.V.
        • Dugani S.B.
        • Akinkuolie A.O.
        • Moorthy M.V.
        • et al.
        Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: the Women's Health Study.
        J. Clin. Lipidol. 2017; https://doi.org/10.1016/j.jacl.2017.06.008
        • Wendt T.
        • Bucciarelli L.
        • Qu W.
        • Lu Y.
        • Yan S.F.
        • et al.
        Receptor for advanced glycation endproducts (RAGE) and vascular inflammation: insights into the pathogenesis of macrovascular complications in diabetes.
        Curr. Atheroscler. Rep. 2002; 4: 228-237
        • Wang M.
        • Zhang J.
        • Jiang L.Q.
        • Spinetti G.
        • Pintus G.
        • et al.
        Proinflammatory profile within the grossly normal aged human aortic wall.
        Hypertension. 2007; 50: 219-227https://doi.org/10.1161/HYPERTENSIONAHA.107.089409
        • Haukeland J.W.
        • Damas J.K.
        • Konopski Z.
        • Loberg E.M.
        • Haaland T.
        • et al.
        Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2.
        J. Hepatol. 2006; 44: 1167-1174https://doi.org/10.1016/j.jhep.2006.02.011
        • Jarrar M.H.
        • Baranova A.
        • Collantes R.
        • Ranard B.
        • Stepanova M.
        • et al.
        Adipokines and cytokines in non-alcoholic fatty liver disease.
        Aliment. Pharmacol. Ther. 2008; 27: 412-421https://doi.org/10.1111/j.1365-2036.2007.03586.x
        • Belmin J.
        • Bernard C.
        • Corman B.
        • Merval R.
        • Esposito B.
        • et al.
        Increased production of tumor necrosis factor and interleukin-6 by arterial wall of aged rats.
        Am. J. Physiol. 1995; 268: H2288-H2293
        • Gerli R.
        • Monti D.
        • Bistoni O.
        • Mazzone A.M.
        • Peri G.
        • et al.
        Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians.
        Mech. Ageing Dev. 2000; 121: 37-46
        • Arner P.
        • Backdahl J.
        • Hemmingsson P.
        • Stenvinkel P.
        • Eriksson-Hogling D.
        • et al.
        Regional variations in the relationship between arterial stiffness and adipocyte volume or number in obese subjects.
        Int. J. Obes. 2015; 39: 222-227https://doi.org/10.1038/ijo.2014.118
        • Ridker P.M.
        From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection.
        Circ. Res. 2016; 118: 145-156https://doi.org/10.1161/CIRCRESAHA.115.306656
        • Interleukin-6 Receptor Mendelian Randomisation Analysis C.
        • Swerdlow D.I.
        • Holmes M.V.
        • Kuchenbaecker K.B.
        • Engmann J.E.
        • et al.
        The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.
        Lancet. 2012; 379: 1214-1224https://doi.org/10.1016/S0140-6736(12)60110-X
        • Collaboration IRGCERF
        • Sarwar N.
        • Butterworth A.S.
        • Freitag D.F.
        • Gregson J.
        • et al.
        Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies.
        Lancet. 2012; 379: 1205-1213https://doi.org/10.1016/S0140-6736(11)61931-4
        • Targher G.
        • Bertolini L.
        • Padovani R.
        • Rodella S.
        • Zoppini G.
        • et al.
        Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease.
        Diabetes Care. 2006; 29: 1325-1330https://doi.org/10.2337/dc06-0135
        • Rafiq N.
        • Bai C.
        • Fang Y.
        • Srishord M.
        • McCullough A.
        • et al.
        Long-term follow-up of patients with nonalcoholic fatty liver.
        Clin. Gastroenterol. Hepatol. 2009; 7: 234-238https://doi.org/10.1016/j.cgh.2008.11.005
        • Soderberg C.
        • Stal P.
        • Askling J.
        • Glaumann H.
        • Lindberg G.
        • et al.
        Decreased survival of subjects with elevated liver function tests during a 28-year follow-up.
        Hepatology. 2010; 51: 595-602https://doi.org/10.1002/hep.23314