Thus, current evidence goes against a linear association of ALT with CVD events. Why GGT may be more strongly linked than ALT to vascular outcomes is not entirely clear. GGT levels may capture processes relevant to atherogenesis, but such observations are currently speculative and further studies are needed. Liver imaging is inevitably a more reliable method for diagnosing NAFLD than elevated liver enzymes; for example, the use of routine ultrasound has been reported to have a sensitivity of 89% and specificity of 93% for the identification of fatty liver.26 However, linkages of liver enzymes with incident events have been more carefully considered in recent meta-analyses as

discussed above. Data from five studies with imaging-diagnosed NAFLD are summarized in Table 2. The individual study end points are not uniform, and have been specified in the table. Two reports related to subjects with T2DM,27, 28 and both are based on the same cohort (the selleck products Valpolicella Heart Diabetes Study). The first

report was a nested case-control selleckchem study for incident CVD events over 5 years and reported an increased risk of events (odds ratio [OR] 1.53, 95% CI 1.1-1.7) after controlling for several risk factors, including the metabolic syndrome.27 The second report used the full cohort data, and the results were broadly similar.28 Of the three remaining imaging studies,29-31 only one had outcomes based on incident CVD events, including both fatal and nonfatal events for a population with NAFLD graded as simple steatosis.30 Among 1,221 participants, 231 had simple steatosis; the incidence of CVD was higher in these 231 subjects (11 CVD events) than in subjects without NAFLD (10 events). Multivariate analyses indicated that NAFLD was a predictor of CVD independent of conventional risk factors (OR 4.12, 95% CI 1.58-10.75, P = 0.004); however, with such small numbers, the CI was inevitably very broad. The last study prospectively followed up 7,372 patients discharged with a diagnosis of fatty liver, using the Danish Death Registry to obtain information on mortality data.29 Comparative general

population data were based on national CVD mortality rates for each sex in 5-year age groups and calendar periods under observation. The standardized mortality ratio (SMR) for CVD in those with fatty liver was 2.1 (95% CI 1.8-2.5). The latter study was limited in its ability MCE to consider the extent to which such excess risk was accounted for by established risk factors. Another study investigated the association of GGT with mortality, assessing whether accompanying ultrasound-determined liver steatosis strengthened the observed associations.31 The study followed subjects (including those with baseline CVD) for a mean of 7.2 years. The association of GGT levels alone with CVD mortality only became significant when comparing subjects with GGT levels in the highest quintile with those in the lowest quintile (HR 1.86, 95% CI 1.10-3.