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Copyright ©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Oct 7, 2014; 20(37): 13306-13324
Published online Oct 7, 2014. doi: 10.3748/wjg.v20.i37.13306
Table 1 Prospective and retrospective studies of the risk of cardiovascular mortality in patients with nonalcoholic fatty liver disease diagnosed by liver biopsy and/or by ultrasonography
Ref.Study designNAFLD patientsDiagnosis of NAFLDMean duration follow-up (yr)Result
Matteoni et al[26], 1999Retrospective, Hospital-based132Histology18.0No adjustment made. Higher all-cause, liver-related mortality but no difference in CVD mortality (NASH vs simple steatosis)
Dam-Larsen et al[21], 2004Retrospective, Hospital-based109Histology16.7Analysis performed by gender. No difference in all-cause and liver-related or CVD mortality (simple steatosis vs general population)
Adams et al[20], 2005Retrospective community-based420US and/or histology7.6Matched for gender, age and country Higher all-causae, liver-related and CVD mortality (CVD is the second cause of death by frequency) in NAFLD patients (especially cirrhosis)
Targher et al[12], 2005Prospective case-control, Hospital-based248/21031US5.0NAFLD was independently associated with increased nonfatal CVD and CVD mortality
Ekstedt et al[5], 2006Retrospective, Hospital-based129Histology13.7Matched for gender, age and country Higher all-cause, liver-related and CVD mortality (NASH but no simple steatosis vs general population)
Hamaguchi et al[28], 2007Prospective, community-based312/16372US5.0NAFLD was independently associated with increased risk of nonfatal CVD events
Targher et al[27], 2007Prospective, Hospital-based1421/21031US6.5NAFLD was independently associated with increased risk of nonfatal CVD events and CVD mortality
Haring et al[29], 2009Prospective, community-based2490/41603US and altered GGT7.3NAFLD was independently associated with increased risk of all-cause and CVD mortality in men
Rafiq et al[22], 2009Retrospective, Hospital-based173Histology13.0No adjustments made Higher liver-related mortality, but no difference in overall mortality (NASH vs simple steatosis)
Söderberg et al[23], 2010Retrospective, Hospital-based118Histology18.0Matched for gender, age and year Higher all-cause, liver-related and CVD mortality (NASH but no simple steatosis vs general population)
Lazo et al[32], 2011Prospective, population-based (third NHANES study population 1988-1994)2089/113714US14.3Independent increased risk of CVD but no increased risk in all-cause, liver-related and CVD mortality
Stepanova et al[33], 2012Prospective, population-based (third NHANES study population 1988-1994)2492/113714US14.3Independent increased risk of CVD but no increased risk in all-cause, liver-related and CVD mortality
Treeprasertsuk et al[31], 2012Prospective, community-based309US, CT, MRI, and or Histology11.5Higher 10-Year CVD risk (NAFLD vs general population)
Kim et al[34], 2013Prospective, population-based (third NHANES study population 1988-1994)4083/111544US and NAFLD Fibrosis Score14.5US-Defined NAFLD was not associated with overall mortality. NAFLD with advanced fibrosis was independently associated with overall mortality (majority of deaths were due to CVD)
Stepanova et al[25], 2013Retrospective, Population-based289Histology6.25No adjustments made Higher risk of liver-related mortality in NASH than non-NASH. NAFLD and type II diabetes highest risk for overall and liver-related mortality
Table 2 Studies of the impaired left ventricular function and disturbance of rhythm in patients with nonalcoholic fatty liver disease
Ref.Study designStudy populationStudy sizeDiagnosis of NAFLDCardiac parameters examinedResults
Left ventricular function
Goland et al[78], 2006Retrospective, Case-control study, Hospital-basedNAFLD vs control38 NAFLD 25 non-NAFLDUS or histologyComplete echocardiographic study, TDI, peak velocities of E and A diastolic filling, E/A ratio, Vp, E', and S' of mitral annulusNAFLD patients had increased thickening of the intraventricular septum and posterior, lower E diastolic filling velocity, lower E/A ratio, longer, lower Vp and lower E' No differences were found according to LV systolic function
Lautamaki et al[79] 2006Retrospective, Case-control study, Hospital-basedPatients with type 2 diabetes and CVD28 low liver fat 27 high liver fat Matched for age, BMI, fasting glucoseH-MRSPositron emission tomography. Myocardial perfusion was measured with[15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-D-glucose during hyperinsulinemic euglycemiaLiver fat content is independently associated with impaired myocardial metabolism
Fallo et al[80] 2009Retrospective, Case-control study, Hospital-basedNever-treated essential hypertensive patients48 NAFLD 38 non-NAFLD Matched for sex, age and blood pressure levelsUSComplete echocardiographic study: TDI, peak velocities of E and A diastolic filling, E/A ratio, Vp, E', and S' of mitral annulusNAFLD patients had increased prevalence of left ventricular hypertrophy , diastolic dysfunction that increased according to the degree of NAFLD
Perseghin et al[81] 2008Retrospective, Case-control study, Hospital-basedYoung non-diabetic men21 fatty liver 21 non fatty liver Matched for age, BMI, blood pressure levels, lipid valuesH-MRSMRI and MRSNo difference in morphological parameters of the LV, systolic and diastolic functions NAFLD patients had reduced values of PCr/ATP ratio
Bonapace et al[17] 2012Retrospective, Case-control study, Hospital-basedPatients with type 2 diabetes32 NAFLD 18 non-NAFLD Matched for age, sex, BMI, waist circumference, hypertension, smoking, diabetes duration, microvascular complication status, medication useUSComplete echocardiographic study, TDI, peak velocities of E and A diastolic filling, E/A ratio, Vp, E', and S' of mitral annulusNAFLD patients had lower E', tissue velocity, higher E-to-e' ratio, higher time constant of isovolumic relaxation, higher LV-end diastolic pressure (EDP), higher LV EDP/end diastolic volume No difference in morphological parameters of the LV, systolic functions
Hallsworth et al[82] 2013Retrospective, Case-control study, Hospital-basedNAFLD and healthy controls19 NAFLD 19 non-NAFLD Matched for age, sex, BMI, weight, and body surface area vs controlH-MRSMRI and MRSNAFLD patients had thicker left ventricular walls at systole and diastole, decreased longitudinal shortening, higher concentric remodelling. No difference in PCr/ATP ratio
Disturbance of cardiac rhythm
Targher et al[19] 2013Prospective, Hospital-basedType 2 diabetes281 NAFLD 119 non-NAFLD Adjustments for age, sex, hypertension and electrocardiographic featuresUS12-lead electrocardiogramNAFLD was associated with an increased risk of incident AF
Table 3 Studies on the association between non-alcoholic fatty liver disease and carotid intima-media thickness in adults: evaluation of the independent predictors for intima-media thickness increase
Ref.cases nCohortNAFLD diagnosis byIndependent predictors for IMT
Brea et al[40] 200580NALFD and matched population controlsUSNAFLD, age, serum ferritin
Volzke et al[41] 20051261 + 2961German populationUSHepatic steatosis
Lonardo et al[129] 2006449Population/NAFLDUSAge
Targher et al[52] 2006145NAFLD and matched healthy controlsBiopsySeverity of histological feature of NAFLD
Targher et al[55] 2006200Type2 diabetes +/- NAFLDUSHOMA-IR
Aygun et al[49] 200880NAFLD and matched healthy controlsUSNAFLD and BMI
Sookoian et al[7] 2008 (Meta-regression analysis)3497SubjectsUSALT, GGT, NAFLD
Fracanzani et al[15] 2008375NAFLD and matched population controlsUS and biopsySteatosis, age and blood pressure
Kim et al[42] 20091021Cross sectionalUSNAFLD with MS
Petit et al[58] 2009101Type 2 diabetesMRSAge, no association with steatosis
Ramilli et al[43] 2009154Referred subjects for abdominal USUSNAFLD
Wang et al[130] 2009170Healthy subjectsUSALT levels
Salvi et al[50] 2010220NAFLD, healthy controlsNAFLD and MS
Mohammadi et al[44] 2011335Male NAFLD controlsUSNAFLD with or without MS
Neri et al[110] 201190Chronic hemodialysis plus steatosis and healthy controlsUS, biopsyHistological steatosis
Valenti et al[131] 2011506NAFLDUSSystolic blood pressure, glucose, LDL, abdominal circumference, age, ferritin
Huang et al[46] 20122590 + 6042Chinese population +/- NAFLDUSNAFLD
Kang et al[47] 2012633Non-diabetic +/- NAFLDUSNAFLD with or without MS
Thakur et al[51] 201280Non-diabetic NAFLD, healthy controlsUSNAFLD
Kim et al[132] 2013769Healthy subjectsUSUpper normal range of ALT in women with NAFLD
Oni et al[13] 2013 Systematic review16 studiesPopulation, cross- sectional, case-controlUS, biopsyPositive association between IMT and NAFLD
Petta et al[126] 2013162 + 267NAFLD and validation cohortBiopsyPNPLA3 polymorphism in younger patients
Kim et al[133] 20144437Type 2 diabetesUSNAFDL with insulin resistance