The MIAMI study (Markers of Inflammation and Atorvastatin effect in previous Myocardial Infarction): results of a prospective, open-label, multicenter study

Objective: To investigate the relationship between changes induced by atorvastatin in carotid IMT (C-IMT) and changes in soluble markers of inflammation, thrombosis and endothelial function. Methods: Patients with stable ischemic heart disease (n=85) were treated with 20 mg/day of atorvastatin for 20±4 months. C-IMT, soluble markers (sVCAM-1, sICAM-1, sE-selectin, IL-6, IL-8, IL-18, TNFα, hsCRP, vWF, CD40L, MMP9, fibrinogen) and lipids were measured at times 0, 12 and 24 months. Results: Atorvastatin induced C-IMT regression (p=0.004 for IMTmean) and significantly reduced plasma levels of triglycerides, total-C, LDL-C, vWF, sICAM-1, sE-selectin fibrinogen (all p<0.0001), IL-8 (p=0.004), MMP9 and TNFα (both p<0.05). HDL-C, IL-6 and CD40L increased in response to therapy (p<0.05), whereas hsCRP, IL-18, and sVCAM-1 did not change. Changes in lipids and in soluble markers were poorly correlated with C-IMTs changes when analyzed singly. In contrast, the combination of changes in soluble markers (soluble marker-score), soluble markers and lipids (total-score) or biologically-related variables (inflammatory-score, interleukin-score and adhesion molecule-score) strongly correlated with the effects of atorvastatin on carotid IMT (p= 0.007, 0.002, 0.04, 0.003 and 0.17, respectively). Conclusion: The anti-atherosclerotic effect of atorvastatin could be explained, at least in part, by pleiotropic effects on markers of inflammation, thrombosis and endothelial dysfunction.