Pregnancy-associated plasma protein-A (PAPP-A) was associated with atherosclerotic plaque vulnerability, whereas statin therapy was associated with increased plaque stability. Eighty-six patients presenting with clinical indications (non-ST-elevation myocardial infarction, unstable angina, and stable angina) for invasive coronary angiography and subsequent verified coronary artery disease (CAD) were randomly assigned in a double-blind manner to atorvastatin 10 or 80 mg/day. PAPP-A, high-sensitivity C-reactive protein (hs-CRP), and lipids were measured at baseline (before statin therapy) and at 1 and 6 months. PAPP-A was significantly increased in 35 patients with acute coronary syndrome (ACS) compared with 51 patients with stable CAD (p <0.001). Patients randomly assigned to atorvastatin 10 mg did not show a significant decrease in PAPP-A from baseline at 1 or 6 months. Patients treated with atorvastatin 80 mg showed a significant decrease at 1 month compared with baseline, but not at 6 months. hs-CRP was not significantly different between the ACS and stable CAD groups. Patients receiving atorvastatin 10 mg showed no hs-CRP decrease at 1 or 6 months, whereas it significantly decreased in the 80-mg group at 6 months, but not at 1 month. In conclusion, PAPP-A significantly increased in patients with ACS compared with those with stable coronary disease. High-dose atorvastatin significantly decreased PAPP-A at 1 month and hs-CRP at 6 months in patients with verified CAD. Low-dose atorvastatin did not produce this effect.