Nonalcoholic fatty liver disease and vascular function: cross-sectional analysis in the Framingham heart study.
OBJECTIVE
Patients with nonalcoholic fatty liver disease (NAFLD) have an increased risk of cardiovascular disease; however, it is not known whether NAFLD contributes to cardiovascular disease independent of established risk factors. We examined the association between NAFLD and vascular function.


RESULTS
We conducted a cross-sectional study of 2284 Framingham Heart Study participants without overt cardiovascular disease who had liver fat attenuation measured on computed tomography and who had measurements of vascular function and covariates. We evaluated the association between NAFLD and vascular function using multivariable partial correlations adjusting for age, sex, cohort, smoking, diabetes mellitus, hyperlipidemia, hypertension, body mass index, and visceral adipose tissue. The prevalence of NAFLD in our sample (mean age, 52±12 years; 51.4% women) was 15.3%. In age-, sex-, and cohort-adjusted analyses, greater liver fat was modestly associated with lower flow-mediated dilation (r=-0.05; P=0.02), lower peripheral arterial tonometry ratio (r=-0.20; P<0.0001), higher carotid-femoral pulse wave velocity (r=0.13; P<0.0001), and higher mean arterial pressure (r=0.11; P<0.0001). In multivariable-adjusted models, NAFLD remained associated with higher mean arterial pressure (r=0.06; P=0.005) and lower peripheral arterial tonometry ratio (r=-0.12; P<0.0001). The association between NAFLD and peripheral arterial tonometry ratio persisted after further adjustment for body mass index and visceral adipose tissue.


CONCLUSIONS
For multiple measures of vascular function, the relationship with NAFLD appeared largely determined by shared cardiometabolic risk factors. The persistent relationship with reduced peripheral arterial tonometry response beyond established risk factors suggests that NAFLD may contribute to microvascular dysfunction.
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Michelle T
MT
Long
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Na
N
Wang
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Martin G
MG
Larson
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Gary F
GF
Mitchell
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Joseph
J
Palmisano
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Ramachandran S
RS
Vasan
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Udo
U
Hoffmann
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Elizabeth K
EK
Speliotes
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Joseph A
JA
Vita
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Emelia J
EJ
Benjamin
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.).
Caroline S
CS
Fox
From the Division of Gastroenterology, Boston Medical Center (M.T.L.), Section of Preventive Medicine, Department of Medicine (R.S.V.), Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section (R.S.V., J.A.V., N.M.H.), Boston University School of Medicine, MA; National Heart, Lung, and Blood Institute's Framingham Heart Study, MA (M.T.L., M.G.L., R.S.V., E.J.B., C.S.F.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); Data Coordinating Center (J.P., N.W.), Department of Epidemiology (E.J.B.), Boston University School of Public Health, MA; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston (U.H.); Division of Gastroenterology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (E.K.S.); and Division of Endocrinology, Hypertension, and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.). nhamburg@bu.edu.
Naomi M
NM
Hamburg
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000792:Angiography / Q000379:methods; D062186:Arterial Pressure; D001900:Boston; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology*; D015897:Comorbidity; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000453:epidemiology*; D015995:Prevalence; D011379:Prognosis; D063177:Pulse Wave Analysis; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D014057:Tomography, X-Ray Computed / Q000379:methods; D059289:Vascular Stiffness
multidetector computed tomography; obesity; risk factors; vascular endothelium