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Does nonalcoholic fatty liver disease cause cardiovascular disease? Current knowledge and gaps

  • Raul D. Santos
    Correspondence
    Corresponding author. Hospital Israelita Albert Einstein, Av. Brasil 953, CEP 01431-000, São Paulo, SP, Brazil.
    Affiliations
    Hospital Israelita Albert Einstein, Sao Paulo, Brazil

    Lipid Clinic Heart Institute (InCor) University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil
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  • Luca Valenti
    Affiliations
    Università Degli Studi Milano, Fondazione IRCCS Ca' Granda Pad Granelli, Milan, Italy
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  • Stefano Romeo
    Affiliations
    Department of Molecular and Clinical Medicine Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
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      Highlights

      • NAFLD is highly prevalent ranging from steatosis to cirrhosis.
      • NAFLD advanced forms associated with cardiovascular risk.
      • NAFLD studies limited by heterogeneity and confounders.
      • Genetic variants predisposing to NAFLD not consistently associated with cardiovascular events.
      • No proof that NAFLD is causal of cardiovascular disease.

      Abstract

      Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and includes a spectrum of abnormalities ranging from steatosis to cirrhosis. In this review, we address recent evidence and limitations of studies that evaluated the association of NAFLD with atherosclerotic cardiovascular disease. NAFLD is considered an ectopic fat deposit associated with metabolic (insulin resistance, hyperglycemia and dyslipidemia), inflammatory, coagulation and blood pressure disturbances. Prospective studies have associated NAFLD presence and severity, particularly steatohepatitis and fibrosis, with an increased risk of cardiovascular disease. However, these studies are limited by heterogeneity concerning NAFLD diagnostic criteria and disease severity stratification, as well as by the presence of confounding factors. In addition, genetic variants predisposing to NAFLD, such as the PNPLA3 I148M mutation, were not consistently associated with an increased risk of cardiovascular events. Therefore, currently, it is not possible to prove a causal relation between NAFLD and cardiovascular disease. Furthermore, there is presently no evidence that NAFLD diagnosis can be used as a tool to improve cardiovascular risk stratification and modify treatment. Specific treatments for NAFLD are being developed and must be tested prospectively in adequately designed trials to determine the potential of reducing both hepatic and cardiovascular diseases and to prove whether NAFLD is indeed a cause of atherosclerosis.

      Graphical abstract

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