Cardiovascular phenotype of nonalcoholic fatty liver disease: Changing the paradigm about the role of distant toxic fat accumulation on vascular disease

SILVIA SOOKOIAN; CARLOS J. PIROLA

HEPATOLOGY (BALTIMORE, MD.)

JOHN WILEY & SONS INC

Lugar: Hoboken; Año: 2012 vol. 56 p. 1185 - 1186

0270-9139

To the Editor: We read with great interest the article by Kim D et al. about the associated between NAFLD and coronary artery calcification (CAC); the authors concluded that NAFLD per se might be an independent risk factor for coronary artery disease because they were able to show that the association was independent of traditional risk factors, including visceral adiposity (VAT) {Kim, 2012 KIM2012 /id}. Actually, the authors highlight this observation as the main strength of their study, as they said that had the unique opportunity to assess the relationship between NAFLD and subclinical coronary atherosclerosis ?above and beyond VAT?. Interestingly, previous research from Framingham Heart Study showed that VAT, BMI, and pericardial fat (PCF) are associated with CAC, but only PCF remains significant following risk factor adjustment, suggesting a locally toxic effect on the vasculature {Rosito, 2008 ROSITO2008 /id}. Thus, the interesting study of Kim D et al leaves still an open a key question about whether the contribution of NAFLD to CAC is also ?above and beyond? PCF. That would be an interesting hypothesis to test.   In addition, the authors suggested that the pathogeneses that relate NAFLD and coronary artery disease have not been thoroughly investigated. We would like to add some comments about this affirmation as we and others have shown that the contribution of fatty liver to an increased cardiovascular risk and a systemic proatherogenic profile is beyond to be regarded as a marker of cardiometabolic disease. Actually, we observed that while NAFLD progresses, the contribution of the liver disease to the atherogenic risk is greater, as the liver of NASH patients not only shows histological changes associated with the disease severity, but also an altered profile of local overexpression of proatherogenic genes {Sookoian, 2011 SOOKOIAN2011A /id}. For instance, we observed a 6.8 fold increase in the liver abundance of    transforming growth factor-â 1 when compared with simple steatosis {Sookoian, 2011 SOOKOIAN2011A /id} , a growth factor associated with high incidence of coronary events, restenosis after coronary intervention, atherosclerosis and even arterial hypertension  {Aihara, 2010 AIHARA2010 /id}, and a 2 fold increase in the liver abundance angiotensin I-converting enzyme. Hence, NAFLD might contribute to the increased risk of cardiovascular disease, included coronary atherosclerosis, through the release of molecular mediators of atherogenesis. This scenario suggests that NAFLD participates in the crosstalk with target organs leading to vascular disease and supposes a change of the classical paradigm about the role of local vs. distant toxic fat accumulation and deleterious vascular effects. Thus, we would take notice about to the potential ?secretory / endocrine? role of NAFLD and its impact on the modulation of systemic phenotypes.