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Hepatic fat as a novel marker for high-risk coronary atherosclerotic plaque features in familial hypercholesterolaemia

  • Gavin Huangfu
    Affiliations
    Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia

    Medical School, The University of Western Australia, Crawley, Western Australia, Australia

    Harry Perkins Institute of Medical Research, Murdoch, Western Australia, Australia
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  • Biyanka Jaltotage
    Affiliations
    Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
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  • Jing Pang
    Affiliations
    Medical School, The University of Western Australia, Crawley, Western Australia, Australia
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  • Nick S.R. Lan
    Affiliations
    Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
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  • Arun Abraham
    Affiliations
    Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
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  • Jacobus Otto
    Affiliations
    Department of Radiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
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  • Abdul R. Ihdayhid
    Affiliations
    Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia

    Medical School, The University of Western Australia, Crawley, Western Australia, Australia

    Harry Perkins Institute of Medical Research, Murdoch, Western Australia, Australia
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  • James M. Rankin
    Affiliations
    Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
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  • Benjamin J.W. Chow
    Affiliations
    Department of Medicine (Cardiology) and Radiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
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  • Gerald F. Watts
    Affiliations
    Medical School, The University of Western Australia, Crawley, Western Australia, Australia

    Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia
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  • Author Footnotes
    1 Oyekoya T. Ayonrinde and Girish Dwivedi share senior author and are equal in contribution to this paper.
    Oyekoya T. Ayonrinde
    Footnotes
    1 Oyekoya T. Ayonrinde and Girish Dwivedi share senior author and are equal in contribution to this paper.
    Affiliations
    Medical School, The University of Western Australia, Crawley, Western Australia, Australia

    Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia

    Faculty of Health Sciences, Curtin University, Bentley, Western Australia, Australia
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  • Author Footnotes
    1 Oyekoya T. Ayonrinde and Girish Dwivedi share senior author and are equal in contribution to this paper.
    Girish Dwivedi
    Correspondence
    Corresponding author at: Wesfarmers Chair in Cardiology and Consultant Cardiologist, Harry Perkins Institute of Medical Research and Fiona Stanley Hospital, The University of Western Australia, Perth, Australia.
    Footnotes
    1 Oyekoya T. Ayonrinde and Girish Dwivedi share senior author and are equal in contribution to this paper.
    Affiliations
    Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia

    Medical School, The University of Western Australia, Crawley, Western Australia, Australia

    Harry Perkins Institute of Medical Research, Murdoch, Western Australia, Australia

    Department of Medicine (Cardiology) and Radiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
    Search for articles by this author
  • Author Footnotes
    1 Oyekoya T. Ayonrinde and Girish Dwivedi share senior author and are equal in contribution to this paper.
Published:November 30, 2022DOI:https://doi.org/10.1016/j.metabol.2022.155370

      Highlights

      • Hepatic fat independently predicts high-risk coronary artery plaque features in FH.
      • Hepatic fat associates with higher low attenuation and non-calcified plaque volumes.
      • CT assessment of hepatic fat may add incremental value to CVD risk stratification.

      Abstract

      Background & aims

      Hepatic steatosis has been associated with increased risk of coronary artery disease. Individuals with familial hypercholesterolaemia have accelerated but variable progression of coronary artery disease. We investigated whether hepatic steatosis is associated with novel coronary atherosclerosis biomarkers in adults with heterozygous familial hypercholesterolaemia, using comprehensive coronary computed tomographic angiography.

      Methods

      We conducted a cross-sectional study of 213 asymptomatic patients with familial hypercholesterolaemia (median age 54.0 years, 59 % female) who underwent coronary computed tomographic angiography for cardiovascular risk assessment in an outpatient clinic. High-risk plaque features, plaque volume and pericoronary adipose tissue attenuation were assessed. From concurrently captured upper abdominal images, severity of hepatic steatosis was computed, as liver minus spleen computed tomography attenuation and stratified into quartiles.

      Results

      Of 213 familial hypercholesterolaemia patients, 59 % had coronary artery calcium, 36 % obstructive coronary artery disease (≥50 % stenosis) and 77 % high-risk plaque features. Increasing hepatic steatosis was associated with higher calcium scores, more high-risk plaque features and presence of obstructive coronary artery disease. Hepatic steatosis was associated with the presence of high-risk plaque features (OR: 1.48; 95 % CI: 1.09–2.00; p = 0.01), particularly in the proximal coronary segments (OR: 1.52; 95 % CI: 1.18–1.96; p = 0.001). Associations persisted on multivariable logistic regression analysis adjusting for cardiometabolic factors, obstructive coronary artery disease and calcium score. Hepatic steatosis was associated with higher plaque volumes (Q4: 499 mm3 vs Q1: 414 mm3, p = 0.02), involving mainly low attenuation and noncalcified plaques (both p = 0.03). No differences in pericoronary adipose tissue attenuation were observed.

      Conclusions

      Hepatic steatosis is associated with multiple indices of advanced coronary atherosclerosis in familial hypercholesterolaemia patients, particularly high-risk plaque features, independent of conventional cardiovascular risk factors and markers. This may involve specific mechanisms related to hepatic steatosis.
      Clinical trial number: N/A.

      Graphical abstract

      Abbreviations:

      ACS (acute coronary syndrome), ASCVD (atherosclerotic cardiovascular disease), BMI (body mass index), CAC (coronary artery calcium), CAD (coronary artery disease), CCTA (computed coronary tomographic angiography), CT (computed tomography), FH (familial hypercholesterolaemia), HDL (high-density lipoprotein), HRP (high-risk plaque), HS (hepatic steatosis), HU (Hounsfield unit), HUL-S (liver attenuation index), IQR (interquartile range), LAD (left anterior descending), LAP (low-attenuation plaque), LDL (low-density lipoprotein), NAFLD (non-alcoholic fatty liver disease), PCAT (pericoronary adipose tissue attenuation), PR (positive remodelling), PV (plaque volume), RCA (right coronary artery), RLP (remnant lipoprotein), SC (spotty calcification)

      Keywords

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