Atorvastatin lowers plasma matrix metalloproteinase-9 in patients with acute coronary syndrome.

Abstract

Atheromatous plaque rupture and subsequent thrombosis are the main causes of acute coronary syndrome (ACS) including acute myocardial infarction (AMI), unstable angina pectoris (UAP), and sudden cardiac death (1)(2). Plaque instability is associated with a high macrophage content and a thin fibrous cap. Matrix metalloproteinases (MMPs) have the capability to degrade the extracellular matrix of the fibrous cap, predisposing to plaque rupture (3). Macrophages are the major source of the MMPs, of which MMP-9 is the most prevalent form. Several lines of evidence suggest that MMP-9 could play a potential role in atheromatous plaque disruption and in the molecular mechanism of ACS (4)(5). Clinical trials have demonstrated that statin therapy reduces cardiovascular events and mortality (6)(7). The MIRACL Study demonstrated that atorvastatin treatment during the acute phase of ACS reduced recurrent ischemic events (8). In addition to the effects on lipid concentrations, stabilization of atherosclerotic plaques and attenuation of the inflammatory response may account for the clinical benefits of statins in ACS. Animal experiments and clinical studies have shown that statins can stabilize plaque by increasing the collagen content and inhibiting metalloproteinases (9)(10)(11). Plaque stabilization could be achieved by direct inhibition of MMPs by statins. For this study, we enrolled 40 patients with ACS (including 17 with AMI and 23 with UAP), who were in their first episode. All of the UAP patients fulfilled the criteria for class IIIB of the Ham and Braunwald (12) classification of unstable angina. The diagnosis of AMI was based on a history of ischemic chest pain, characteristic electrocardiographic changes, and increased creatine kinase-MB activity at least twice the upper reference limit (>48 U/L) within 24 h after the onset of pain. Exclusion criteria included body temperature >38.0 °C, severe heart failure (NYHA class 3 …