Background: We evaluated the relationship between pregnancy-associated plasma protein-A (PAPP-A) and coronary plaque instability as assessed by intravascular ultrasound (IVUS). Methods: We performed greyscale IVUS analysis in culprit lesions of 93 patients with unstable angina (UA) and 72 with stable angina (SA). A sandwich enzyme-linked immunosorbent assay technique was used to assay circulating PAPP-A. Results: Patients with UA had higher PAPP-A levels than those with SA 10.8 mIU/l [interquartile range (IQR) 8.3-14.4] vs. 5.4 (IQR 2.9-9.8) mIU/l, p < 0.001]. Lesions in patients with higher PAPP-A levels were associated with larger plaque burden than lesions in patients with lower PAPP-A levels. IVUS attenuated plaque, positive remodeling and plaque rupture. Thrombus and angiographic Ambrose type-II eccentric lesions or multiple irregularities were more common in patients with higher PAPP-A levels than in those with lower PAPP-A levels. They were also more common in patients with UA and higher PAPP-A levels than in patients with (1) SA and higher PAPP-A levels, (2) UA and lower PAPP-A levels or (3) SA and lower PAPP-A levels. Conclusions: Higher PAPP-A levels were associated with coronary plaque instability in vivo and unstable symptoms in patients with coronary artery disease. (C) 2013 S. Karger AG, Basel