title: Bi-directional analysis between fatty liver and cardiovascular disease risk factors.
abstract: The relations of non-alcoholic fatty liver disease to cardiovascular disease (CVD) risk factors are not fully understood. The objective of our study is to explore the bi-directional relationships of fatty liver to CVD risk factors.
  
  
  
  We prospectively evaluated whether liver fat predicted the development of CVD risk factors and whether CVD risk factors predicted new onset fatty liver during 6years of follow-up in middle- to older-aged Framingham Heart Study participants. We estimated liver fat using multi-detector computed tomography.
  
  
  
  We included 1051 participants (mean age 45±6years, 46% women). The prevalence of fatty liver was 18% at baseline. In participants without fatty liver at baseline, 101 participants developed incident fatty liver over approximately 6years. Baseline liver fat (per standard deviation increase) was associated with increased odds of incident hypertension (OR 1.42; 95% CI 1.15-1.76; p=0.001) and incident type 2 diabetes (OR 1.43; 95% CI 1.09-1.88, p<0.001). In a parallel analysis, individuals with hypertension (OR 3.34; 95% CI 2.04-5.49), hypertriglyceridemia (OR 3.04; 95% CI: 1.84-5.02), impaired fasting glucose (OR 2.92; 95% CI 1.76-4.82), or type 2 diabetes (OR 4.15; 95% CI 1.19-14.46) at baseline had higher odds of incident fatty liver compared to individuals without those conditions (all p<0.03). In both analyses, the observed associations remained similar after additional adjustments for measures of adiposity.
  
  
  
  The present study demonstrated bi-directional relationships between fatty liver and CVD risk factors among middle- to older-aged Framingham Heart Study participants.
  
  
  
  It is not fully understood whether non-alcoholic fatty liver (NAFLD) disease precedes or develops after increased cardiovascular disease (CVD) risk factors. The findings of our study suggest a bi-directional relationship between NAFLD and CVD risk factors.
authors.affiliation: The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Ma
authors.affiliation: The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.affiliation: The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States.
authors.forename: Alison
authors.initials: A
authors.lastname: Pedley
authors.affiliation: The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States; Department of Mathematics and Statistics, Boston University, Boston, MA, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.affiliation: Radiology Department, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States; Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States; Evans Department of Medicine, Whitaker Cardiovascular Institute and Cardiology Section, Boston University School of Medicine, Boston, MA, United States.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: The Framingham Heart Study, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA, United States; Division of Endocrinology and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.affiliation: Division of Gastroenterology, Evans Department of Medicine, Boston University School of Medicine, Boston, MA, United States. Electronic address: mtlong@bu.edu.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Long
mesh_terms: D050154:Adiposity; D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology*; D015995:Prevalence; D012307:Risk Factors; D014481:United States
keywords: Cardiovascular disease risk factors; Hypertension; Hypertriglyceridemia; Impaired fasting glucose; Metabolic syndrome; Non-alcoholic fatty liver; Type 2 diabetes