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Betatrophin, also called angiopoietin-llike protein 8, is a recently identified adipokine, mainly produced in liver and adipose tissue, which is recognized to play a dual role in lipid and glucose metabolism. However, any association between plasma betatrophin levels and atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), has not been elucidated yet. We investigated plasma betatrophin levels by ELISA in 457 patients (pts) undergoing elective coronary angiography who also had ankle-brachial index (ABI) test for PAD screening. Pts with ACS or a history of PCI were excluded. Results: Of the 457 study pts, CAD was present in 241 (53%), of whom 99 had 1-vessel, 71 had 2-vessel, 71 had 3-vessel disease (3-VD). Plasma betatrophin levels were higher in 241 pts with CAD than in 216 without CAD (median 1120 vs. 909 pg/mL, P<0.001). A stepwise increase in betatrophin levels was found depending on the number of >50% stenotic coronary vessels: 909 in CAD(-), 962 in 1-VD, 1097 in 2-VD and 1393 pg/mL in 3-VD (P<0.001). Betatrophin levels also correlated with the numbers of >50% and >25% stenotic coronary segments (r=0.22 and r=0.24, P<0.001). Moreover, betatrophin levels correlated with HbA1c (r=0.18, P<0.001) but not with FPG and triglyceride levels. In multivariate analysis, betatrophin levels were not a factor for CAD but were a significant factor for 3-VD independent of atherosclerotic risk factors. Odds ratio for 3-VD was 1.06 (95%CI=1.01-1.11, P<0.02) for a 100 pg/mL increase in betatrophin levels. Of the 457 pts, PAD (ABI<0.9) was found in 41 (9%). Betatrophin levels were also higher in 41 pts with PAD than in 416 without PAD (median 1354 vs. 981 pg/mL, P<0.001). Notably, pts with PAD more often had CAD (85% vs. 65%), especially 3-VD (46% vs. 13%) (P<0.001). In multivariate analysis, betatrophin levels were a significant factor for PAD independent of atherosclerotic risk factors and CAD. Odds ratio for PAD was 1.08 (95%CI=1.01-1.14, P<0.02) for a 100 pg/mL increase in betatrophin levels. Conclusions: Plasma betatrophin levels were found to be associated with the presence and severity of CAD as well as PAD independent of atherosclerotic risk factors. Betatrophin may play a role in the development of atherosclerotic diseases. [ABSTRACT FROM AUTHOR]