Nesfatin-1 is a recently identified anorexigenic peptide derived from nucleobindin 2, which is mainly secreted from brain and adipose tissue. Although nesfatin-1 was suggested to have anti-inflammatory and anti-apoptotic properties, the association between plasma nesfatin-1 levels and atherosclerotic disease, such as coronary artery disease (CAD), has not been elucidated. We investigated plasma nesfatin-1 levels by ELISA in 302 patients (pts) undergoing elective coronary angiography for suspected CAD. Pts with ACS, heart failure, malignancy or a history of PCI were excluded. The severity of CAD was represented as the numbers of >50% stenotic vessels and segments, and the severity score of stenosis. The degree of coronary stenosis in each segment was scored 0 to 4 points (0, ≤25%; 1, 26-50%; 2, 51-75%; 3, 76-90%; 4, >90% stenosis), and the severity score was defined as the sum of scores of all segments. Results: Of the 302 study pts, CAD was present in 172 (57%), of whom 67 had 1-vessel, 49 had 2-vessel, 56 had 3-vessel disease (3-VD). Compared with 130 pts without CAD, 172 with CAD more often had hypertension, hyperlipidemia and DM (P<0.05). Plasma nesfatin-1 levels were higher in pts with CAD than without CAD (median 0.21 vs. 0.17 ng/mL, P<0.01). A stepwise increase in nesfatin-1 levels was found depending on the number of >50% stenotic coronary vessels: 0.17 in CAD(-), 0.20 in 1-VD, 0.21 in 2-VD and 0.22 ng/mL in 3-VD (P<0.05). High nesfatin-1 level (>0.19 ng/mL) was found in 43% of pts with CAD(-), 55% of 1-VD, 55% of 2-VD and 68% of 3-VD (P<0.05). Nesfatin-1 levels also correlated with the number of stenotic segments and the severity score (r=0.14 and r=0.13, P<0.02), but they did not correlate with body mass index or HbA1c level. In multivariate analysis, nesfatin-1 levels were a significant factor associated with CAD, especially 3-VD, independent of atherosclerotic risk factors. The odds ratios for CAD and 3-VD were 1.71 (95%CI=1.01-2.91) and 1.96 (95%CI=1.02-3.76) for high nesfatin-1 level of >0.19 ng/mL (P<0.05). Conclusions: Plasma nesfatin-1 levels were found to be associated with the presence and severity of CAD independent of atherosclerotic risk factors. High nesfatin-1 levels in CAD pts may be aimed at preventing the progression of coronary atherosclerosis. [ABSTRACT FROM AUTHOR]