Independent Association between Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: A Systematic Review and Meta-Analysis.

Nonalcoholic fatty liver disease (NAFLD) is closely correlated with insulin resistance and several metabolic syndrome features, but whether it could increase the risk of cardiovascular disease remains undefined. To assess the association between NAFLD and the risk of cardiovascular outcomes, we systematically searched the MEDLINE, Embase, and the Cochrane Library database (1947 to October 2012) by using Medical Subject Heading search terms and a standardized protocol. Randomized controlled trials, case-control, and prospective studies carried out in human adults, in which the unadjusted and multivariate adjusted odds ratios with corresponding 95% confidence interval (CI) for cardiovascular disease with NAFLD were reported. The search yielded 4 cross-sectional studies and 2 prospective cohort studies including 7,042 participants. The pooled effects estimate showed that NAFLD was a predictor of cardiovascular disease (odds ratio 1.88, 95% CI, 1.68 to 2.01; P < 0.001). The random effects summary estimate indicated that NAFLD retained a significant association with cardiovascular outcomes independent of conventional risk factors after adjustment for established cardiovascular risk factors (odds ratio 1.50, 95% CI, 1.21 to 1.87; P < 0.001). These results indicate that NAFLD is a strong independent predictor of cardiovascular disease and may play a central role in the cardiovascular risk of metabolic syndrome.