The role of autoantibody against oxidized low-density lipoprotein (LDL) in the pathogenesis of atherosclerosis is still unknown. The purpose of this study was to determine whether autoantibodies against malondialdehyde (MDA)-modified LDL are associated with coronary artery disease (CAD) and clinical presentations of CAD in non-diabetic patients without acute myocardial infarction (AMI). We determined the serum levels of autoantibody against MDA-modified LDL by ELISA in 71 patients with angiographically significant CAD (> or = 50% diameter stenosis in at least 1 vessel) and 80 controls without angiographically significant CAD. Among the total 151 subjects, 30 subjects did not have any clinical ischemic event, 90 subjects had stable angina symptoms, and 31 subjects had unstable angina symptoms. The autoantibody titer, expressed mean optical density units, was significantly higher in patients with CAD than in controls (0.177 +/- 0.014 versus 0.127 +/- 0.011, respectively; p=0.006) and higher in unstable angina group than in stable angina group (0.240 +/- 0.025 versus 0.145 +/- 0.007, respectively; p < 0.001). By logistic regression analysis, the high autoantibody titer was associated significantly with CAD (P=0.008), independent of age, gender, body mass index, triglyceride concentration, and the ratio of total cholesterol-high density lipoprotein (HDL) cholesterol. In multiple regression analysis, presence of CAD, smoking history and low HDL-cholesterol level were independent factors associated with a increased anti-oxLDL Ab titer. The autoantibody titer was significantly lower in nonsmoker than smoker (p=0.019) and higher in low HDL- cholesterol (< or = 35 mg/dl) group than in high HDL-cholesterol group (p=0.012). Elevated autoantibody titer was associated with CAD and the unstable clinical presentation of CAD. Our results suggest that immune response to oxidized LDL may play a role in the pathogenesis of atherosclerosis and plaque instability.