title: Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study.
abstract: OBJECTIVE
  Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and is associated with development of metabolic disease including atherosclerotic cardiovascular disease (CVD). Our aim is to examine the association of hepatic steatosis with prevalent clinical and subclinical CVD outcomes in a large community-based sample, the Framingham Heart Study.
  
  
  METHODS
  Hepatic steatosis was measured in 3529 participants using multidetector computed tomography scanning. Multivariable logistic regression was used to determine whether hepatic steatosis is associated with prevalent CVD adjusted for covariates. We also tested whether associations were independent of other metabolic diseases/traits. The primary clinical outcome was composite prevalent clinical CVD defined by prior non-fatal myocardial infarction, stroke, transient ischemic attack, heart failure, or peripheral arterial disease. Subclinical cardiovascular outcomes were coronary artery calcium (CAC) and abdominal artery calcium (AAC).
  
  
  RESULTS
  3014 participants were included (50.5% women). There was a non-significant association of hepatic steatosis with clinical CVD (OR 1.14 [p=0.07]). Hepatic steatosis was associated with both CAC and AAC (OR 1.20 [p<0.001] and OR 1.16 [p<0.001], respectively). Associations persisted for CAC even when controlling for other risk factors/metabolic diseases, but for AAC, the associations became non-significant after adjustment for visceral adipose tissue. The association between hepatic steatosis and AAC was stronger in men than in women (p sex interaction=0.022).
  
  
  CONCLUSIONS
  There was a significant association of hepatic steatosis with subclinical CVD outcomes independent of many metabolic diseases/traits with a trend towards association between hepatic steatosis and clinical CVD outcomes. The association with AAC was stronger in men than in women.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Mellinger
authors.affiliation: Statistics and Consulting Unit, Boston University, Boston, MA, United States.
authors.forename: Karol M
authors.initials: KM
authors.lastname: Pencina
authors.affiliation: Department of Statistics, Boston University School of Public Health, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.affiliation: Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: Department of Neurology, Boston University, United States; National Heart, Lung, and Blood Institute's Framingham Heart Study, United States.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study, United States; National Heart, Lung, and Blood Institute Division of Intramural Research, United States.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.affiliation: Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; National Heart, Lung, and Blood Institute's Framingham Heart Study, United States; National Heart, Lung, and Blood Institute Division of Intramural Research, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, United States; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States. Electronic address: espeliot@med.umich.edu.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Speliotes
mesh_terms: D000273:Adipose Tissue / Q000000981:diagnostic imaging / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology
keywords: Abdominal aortic calcium; Cardiovascular disease; Coronary artery calcium; Fatty liver