38 Thus, a CAC score of zero is associated with a very low risk
of subsequent coronary events,38, 39 whereas an elevated CAC score is related to a stepwise increase in the risk of subsequent coronary events.11, 38 CAC scores have been shown to be highly predictive of future cardiovascular events independent of traditional risk AUY-922 chemical structure factors.11, 40, 41 Thus, in this study, we used the CAC score as an outcome variable to predict future coronary heart disease in individuals with NAFLD. Currently, three published papers address the relationship between NAFLD and CAC. But, these results conflict with each other. As part of the Diabetes Heart Study, McKimmie et al.42 suggested that hepatic steatosis is less likely to be a direct mediator of cardiovascular disease and may be described as an epiphenomenon. The preponderance of diabetes (82.8%) and the nature of the Diabetes Heart Study as a family study, however, may limit the generalizability of these BMS-777607 ic50 results. On the contrary, Chen et al.43 reported a significant relationship between NAFLD and CAC in Taiwan, but the possibility of selection bias was raised because of the exclusion of a large number of subjects without hepatic imaging. Jung et al.44 also suggested that hepatic steatosis and increased ALT are associated with CAC. They used less stringent
criteria to define ALT elevation for women and only a single cutoff point of CAC (>100). Importantly, Beta adrenergic receptor kinase two studies did not include VAT data in multivariate analysis. Although the pathogeneses that relate NAFLD and coronary artery disease
have not been thoroughly investigated, several possible explanations have been offered. A low-grade systemic and hepatic inflammatory milieu may link NAFLD to atherosclerosis, which increases the risk of coronary artery disease.45, 46 In NAFLD, reactive oxygen radicals may induce the production of cytokines, such as tumor necrosis factor-α and interleukin-6,47 and add further atherogenic stimuli to the already high oxidative and proinflammatory status that is closely related to metabolic syndrome.48, 49 In addition, such conditions favor the up-regulation of hepatic C-reactive protein levels, which may link NAFLD to coronary atherosclerosis.45, 50 Furthermore, subjects with NAFLD have reduced serum adiponectin levels, which are inversely related to the severity of NAFLD histology.3, 51 Low serum adiponectin levels may also play an important role in the pathogenesis between NAFLD and subclinical coronary atherosclerosis. The strengths of our study are the use of CAC scores, CT-measured VAT, with a high degree of validity and reproducibility, high-quality data collected by trained personnel with a systematic protocol, a wealth of metabolic variables, and a large number of subjects. In addition, we simultaneously measured CAC, hepatic ultrasonography, and VAT on the same day.