Abstract 2840: Pregnancy Associated Plasma Protein-A Elevation in Patients with Acute Myocardial Infarction and Subsequent Atorvastatin Therapy: A Dual-Dose, Double-Blind, Randomized Study
Background: Pregnancy associated plasma protein-A (PAPP-A) is associated with vascular inflammation and is a potential biomarker of coronary artery plaque vulnerability. We hypothesized that PAPP-A levels would be increased in patients presenting with chest pain who subsequently were found have myocardial infarction. Since statins reduce vascular inflammation, we also hypothesized that statin therapy would reduce PAPP-A levels in patients with coronary artery disease. We thus measured PAPP-A, high sensitivity C-reactive protein (hs-CRP), and lipid levels in patients with coronary artery disease randomized to low or high dose atorvastatin treatment.
Methods: 93 patients who presented for coronary angiography with anginal symptoms were evaluated for acute myocardial infarction. Patients with angiographically verified coronary artery disease were then randomized in a double-blind study to receive either 10 or 80 milligrams of oral atorvastatin daily. PAPP-A, hs-CRP, and lipid profiles were measured at baseline, 1 month, and 6 months.
Results: PAPP-A levels were significantly increased in 18 patients with acute myocardial infarction compared to 66 patients with troponin negative status (3.11 mIU/L vs 1.31 mIU/L, p-value 0.004). In the 69 patients who completed 1 month follow up, atorvastatin significantly reduced PAPP-A levels in both treatment groups. Patients randomized to 10 mg had a 36% reduction (1.69 ± 1.70 mIU/L at baseline to 1.07 ± 1.11 mIU/L at 1 month, p-value 0.004). The 80 mg group showed a 60% reduction (1.60 ± 2.02 mIU/L at baseline to 0.72 ± 0.59 mIU/L at 1 month, p-value 0.009). PAPP-A levels showed a decrease proportional to the initial elevation as patients with initial levels less than 2 mIU/L averaged a 12% reduction while those with initial levels greater than 2 mIU/L averaged a 60% reduction. Hs-CRP levels were reduced by 63% and 77% in the 10 and 80 mg groups respectively.
PAPP-A levels in patients presenting with acute myocardial infarction are more than double compared to levels in patients without troponin elevation.
Atorvastatin reduces PAPP-A levels proportionally to the initial elevation and in a dose dependent fashion.
This suggests moderation of coronary inflammation and possible enhanced plaque stability.