Effect of Intensive Atorvastatin Therapy on Prostaglandin E₂ Levels and Metalloproteinase-9 Activity in the Plasma of Patients With Non-ST-Elevation Acute Coronary Syndrome^†

Inflammation plays a pivotal role in the pathophysiology of non–ST elevation acute coronary syndromes (NSTEACS). Intensive statin therapy reduces the recurrence of cardiovascular events after acute coronary syndromes. The aim of this study was to examine nuclear factor–κB activity in peripheral blood mononuclear cells, prostaglandin E₂ (PGE₂) and leukotriene B₄ levels, and matrix metalloproteinase–9 (MMP-9) activity in plasma from patients with NSTEACS (at 0 days, 4 days, 2 months, and 6 months), patients with stable coronary artery disease, and healthy controls. On day 4, patients with NSTEACS were randomized to receive atorvastatin 80 mg/day (n = 14) or standard treatment (n = 16) during 2 months to study its effect on these parameters. Nuclear factor–κB activity (by electrophoretic mobility shift assay), PGE₂ levels (by enzyme-linked immunosorbent assay), and MMP-9 activity (by gelatin zymography) in the plasma of patients with NSTEACS were significantly increased compared with patients with coronary artery disease and healthy controls. At 6 months, MMP-9 activity was normalized, whereas nuclear factor–κB activity and PGE₂ levels were still increased. Leukotriene B₄ plasma levels (by enzyme-linked immunosorbent assay) were similar in patients with NSTEACS and those with coronary artery disease but were significantly higher than those of healthy subjects. There was a significant correlation between plasma PGE₂ levels and MMP-9 activity in patients with NSTEACS (r = 0.754, p <0.01). Atorvastatin 80 mg/day reduced circulating PGE₂ levels (median 222.4 [interquartile range 157.4 to 253.5] vs 550.8 [276.9 to 613.0] pg/ml, p = 0.006) and MMP-9 activity (0.0025 [0.0017 to 0.0035] vs 0.0280 [0.0057 to 0.0712] arbitrary units, p = 0.03). In conclusion, nuclear factor–κB activity in peripheral blood mononuclear cells, and plasma PGE₂ levels and MMP-9 activity, increase during NSTEACS. Atorvastatin 80 mg/day normalizes PGE₂ levels and MMP-9 activity, providing additional mechanisms by which intensive atorvastatin therapy may reduce the incidence of cardiovascular events.

• † Conflicts of interest: Drs. Egido and Tuñón have participated on advisory boards and have been invited speakers for Pfizer.