Background : Synergistic interactions between elevated serum lipoprotein(a) [Lp(a)] and other unfavorable risk factors have been proposed to cause very high risk for coronary artery disease (CAD). The aim of this study was to examine the potential interactions between Lp(a) and other risk factors. Methods : The profiles of serum (apo)(lipo)proteins, markers of inflammation, indicators of hemoconcentration as well as classical risk factors were determined in 264 clinically stable angiographically documented subjects. Correlation, linear and logistic regression and stratification analyses were performed. Results : The frequency and severity of CAD and the prevalence of diabetes mellitus were significantly higher in the 3rd relative to 1st tertile of Lp(a). Subjects with Lp(a) levels in the upper tertile had significantly higher levels of serum glucose, total cholesterol and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), calcium, phosphate and their ion product. Bivariate correlation analysis indicated that serum Lp(a) was associated positively with the occurrence and severity of CAD, diabetes mellitus and the levels of serum glucose, cholesterol, LDL-C, apoB, calcium, phosphate and inversely to physical inactivity. In linear regression analysis, LDL-C (or apoB), diabetes, physical inactivity and phosphate were the major independent determinants of Lp(a) values. In multiple logistic regression analysis, after adjusting for major risk factors, Lp(a) showed a significant and independent association with the prevalence of CAD. By constructing dummy combined variables, elevated Lp(a) accompanied with diabetes or high levels of serum glucose, apoB and cholesterol exhibited an amplified high risk for CAD. Conclusions : The results indicate that serum Lp(a) does interact multiplicatively with diabetes, apoB and cholesterol. The simultaneous assessment of Lp(a) and interactive risk factors enhances the discriminating value for CAD. Clin Chem Lab Med 2008;46:667–73.