This study investigated whether lipoprotein(a) [Lp(a)] is an acute-phase reactant that can cause important bias in risk factor analysis for coronary heart disease among patients with an acute-phase response (APR patients). To determine whether serum Lp(a) concentrations increase among APR patients, we compared the Lp(a) concentrations and apolipoprotein(a) [apo(a)] phenotypes of 100 controls with those of a random sampling of 100 APR patients. Serum Lp(a) concentration was measured by ELISA; Lp(a) phenotyping was performed by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel. Lp(a) was significantly (P <0.0001) higher among APR patients (mean +/- SD 0.300 +/- 0.284 g/L) than among controls (0.118 +/- 0.193 g/L) even though the distribution of apo(a) phenotypes did not differ significantly. The 100 APR patients were grouped into 4 categories: 48 patients with infections, 25 postoperative patients, 17 patients with tumors, and 10 patients with other diseases, all of whom showed substantially higher Lp(a) values than did the controls. For the S5, S4S5, S5S5, and S4 phenotypes, the mean concentrations of serum Lp(a) were substantially higher among the APR patients.