Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence?

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common forms of chronic liver disease worldwide and its prevalence is expected to continue rising. NAFLD has traditionally been considered a consequence of metabolic syndrome (MetS). However, the link between NAFLD and MetS components, especially type 2 diabetes mellitus (T2DM), hypertension (HTN), and cardiovascular disease (CVD) is more complex than previously thought. Indeed, the adverse effects of NAFLD extend far beyond the liver, with a large body of clinical evidence now suggesting that NAFLD may precede and/or promote the development of T2DM, HTN and atherosclerosis/CVD. The risk of developing these cardiometabolic diseases parallels the underlying severity of NAFLD. Accumulating evidence suggests that the presence and severity of NAFLD is associated with an increased risk of incident T2DM and HTN. Moreover, long-term prospective studies indicate that the presence and severity of NAFLD independently predicts fatal and nonfatal CVD events. In this review, we critically discuss the rapidly expanding body of clinical evidence that supports the existence of a bi-directional relationship between NAFLD and various components of MetS, particularly T2DM and HTN, as well as the current knowledge regarding a strong association between NAFLD and CVD morbidity and mortality. Finally, we discuss the most updated putative biological mechanisms through which NAFLD may contribute to the development of HTN, T2DM and CVD.