Markers of inflammation, thrombosis and endothelial activation correlate with carotid IMT regression in stable coronary disease after atorvastatin treatment

Background and aims: MIAMI is a prospective multicenter clinical study designed to investigate the relationship between changes in carotid intima-media thickness (C-IMT) and changes in circulating markers of inflammation, thrombosis and endothelial activation in stable coronary patients treated for 20 ± 3.7 months with 20 mg/day atorvastatin. Methods and results: Eighty-five subjects had their C-IMT, blood lipids and soluble markers measured at baseline, at the 12th month and at the end of the study. Almost all soluble markers decreased upon treatment except for high-sensitivity C-reactive protein (hs-CRP), interleukin-18 (IL-18), tissue factor pathway inhibitor-free (TFPI-free) and soluble vascular cell adhesion molecules-1 (sVCAM-1) which did not change significantly, and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and soluble CD40 ligand (sCD40L) which increased. sCD40L, fibrinogen, tissue factor pathway inhibitor-total (TFPI-total), soluble intercellular adhesion molecules-1 (sICAM-1), sE-selectin, interleukin-8 (IL-8) and von Willebrand factor (vWF) changed significantly even after application of the Bonferroni correction for multiple comparisons. Changes in lipids did not correlate with C-IMT regression either when considered singly or when combined in a lipid score. Changes in soluble markers correlated poorly with C-IMT regression when analyzed singly, but strongly when combined in relevant composite scores (inflammation/coagulation score, endothelial activation score, soluble markers score and total score). Conclusion: In patients with stable coronary artery disease treated with moderate doses of atorvastatin, carotid IMT regression correlated with changes of inflammation, thrombosis and endothelial activation profiles.