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Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study

  • Jessica L. Mellinger
    Affiliations
    Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, United States
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  • Karol M. Pencina
    Affiliations
    Statistics and Consulting Unit, Boston University, Boston, MA, United States
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  • Joseph M. Massaro
    Affiliations
    Department of Statistics, Boston University School of Public Health, United States
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  • Udo Hoffmann
    Affiliations
    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
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  • Sudha Seshadri
    Affiliations
    Department of Neurology, Boston University, United States

    National Heart, Lung, and Blood Institute’s Framingham Heart Study, United States
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  • Caroline S. Fox
    Affiliations
    National Heart, Lung, and Blood Institute’s Framingham Heart Study, United States

    National Heart, Lung, and Blood Institute Division of Intramural Research, United States
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  • Christopher J. O’Donnell
    Affiliations
    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
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  • Elizabeth K. Speliotes
    Correspondence
    Corresponding author. Address: Division of Gastroenterology and Hepatology, University of Michigan Health System, 3912 Taubman Center, 1500 E. Medical Center Drive, SPC 5362, Ann Arbor, MI 48109-5362, United States. Tel.: +1 734 936 4785; fax: +1 734 763 2535.
    Affiliations
    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
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Published:March 14, 2015DOI:https://doi.org/10.1016/j.jhep.2015.02.045

      Background & Aims

      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).

      Conclusion

      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.

      Graphical abstract

      Abbreviations:

      AAC (abdominal aortic calcium), ATP (Adult Treatment Panel), BMI (body mass index), CAC (coronary artery calcium), CHD (coronary heart disease), CT (computed tomography), CVD (cardiovascular disease), HDL (high-density lipoprotein), HRT (hormone replacement therapy), HTN (hypertension), MI (myocardial infarction), NAFLD (non-alcoholic fatty liver disease), NASH (non-alcoholic steatohepatitis), NCEP (National Cholesterol Education Program), PAD (peripheral arterial disease), RNA (ribonucleic acid), SAT (subcutaneous adipose tissue), TIA (transient ischemic attack), VAT (visceral adipose tissue)

      Keywords

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