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The progression and regression of metabolic dysfunction-associated fatty liver disease are associated with the development of subclinical atherosclerosis: A prospective analysis

  • Author Footnotes
    1 Contributed equally.
    Shanshan Liu
    Footnotes
    1 Contributed equally.
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Author Footnotes
    1 Contributed equally.
    Jialu Wang
    Footnotes
    1 Contributed equally.
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Shujing Wu
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Jingya Niu
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Ruizhi Zheng
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Lizhan Bie
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Zhuojun Xin
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Shuangyuan Wang
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Hong Lin
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Zhiyun Zhao
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Tiange Wang
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Min Xu
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Jieli Lu
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Yuhong Chen
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Yiping Xu
    Affiliations
    Clinical Trials Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Weiqing Wang
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Guang Ning
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Yufang Bi
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Mian Li
    Correspondence
    Corresponding authors at: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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  • Yu Xu
    Correspondence
    Corresponding authors at: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
    Affiliations
    Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally.

      Highlights

      • MAFLD was associated with higher risks of developing subclinical atherosclerosis.
      • MAFLD regression modified the risks of subclinical atherosclerosis.
      • The modified effects were more evident in those with low probability of fibrosis or less metabolic risk factors.

      Abstract

      Background

      Metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed and diagnosed based on modified criteria. However, evidence for the risks of developing subclinical atherosclerosis with MAFLD transitions according to its new definition has never been reported.

      Methods

      Using data from a community-based cohort, 6232 participants aged 40 years or older were included and were followed up for a median of 4.3 years during 2010–2015. Participants were categorized into four groups (stable non-MAFLD, MAFLD regressed to non-MAFLD, non-MAFLD progressed to MAFLD, and stable MAFLD). Subclinical atherosclerosis was defined as elevated carotid intima-media thickness (CIMT), elevated brachial-ankle pulse wave velocity (ba-PWV), or microalbuminuria.

      Results

      Compared with the stable non-MAFLD category, participants who progressed to MAFLD at follow-up visit had a 1.356-fold increased risk of developing elevated CIMT [odds ratio (OR) = 1.356; 95% confidence interval (CI) = 1.134–1.620], and a 1.458-fold increased risk of incident microalbuminuria (OR = 1.458; 95% CI = 1.034–2.056) after adjustment for confounders, respectively. In addition, participants with stable MAFLD showed 17.6%, 32.4%, and 35.4% increased risks of developing elevated CIMT, elevated ba-PWV and microalbuminuria, respectively. Compared with the stable MAFLD category, participants with MAFLD and low probability of fibrosis at baseline who regressed to non-MAFLD at follow-up visit had a 29.4% decreased risk of developing elevated CIMT (OR = 0.706; 95% CI = 0.507–0.984), a 43.1% decreased risk of developing elevated ba-PWV (OR = 0.569; 95% CI = 0.340–0.950), but was not significantly associated with incident microalbuminuria (OR = 0.709; 95% CI = 0.386–1.301). The decreased risks attributed to MAFLD regression were more evident in participants without diabetes or dyslipidemia, as well as in those with 0–1 metabolic risk abnormalities, respectively.

      Conclusions

      MAFLD was significantly associated with higher risks of developing subclinical atherosclerosis. Moreover, the regression of MAFLD might modify the risks of developing subclinical atherosclerosis, especially among those with low probability of fibrosis or less metabolic risk abnormalities. Since 40% of baseline participants with missing data on MAFLD measurement at follow-up were excluded, the conclusions should be speculated with caution.

      Abbreviations:

      ABI (ankle-brachial index), UACR (urinary albuminuria-to-creatinine ratio), ADA (American Diabetes Association), ALT (alanine aminotransferase), AST (aspartate aminotransferase), ba-PWV (brachial-ankle pulse wave velocity), BMI (body mass index), BP (blood pressure), CIMT (carotid intima-media thickness), CKD (chronic kidney disease), CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), CVD (cardiovascular disease), DBP (diastolic blood pressure), DM (diabetes mellitus), eGFR (estimated glomerular filtration rate), FIB-4 index (Fibrosis-4 index), FPG (fasting plasma glucose), HbA1c (glycated hemoglobin), HDL-c (high-density lipoprotein cholesterol), HOMA-IR (homeostasis model assessment of insulin resistance), LDL-c (low-density lipoprotein cholesterol), MAFLD (metabolic dysfunction-associated fatty liver disease), NAFLD (nonalcoholic fatty liver disease), SBP (systolic blood pressure), TC (total cholesterol), TG (triglycerides), WC (waist circumference)

      Keywords

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