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

Abstract 

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±3.7months with 20mg/day atorvastatin.

Methods and results

Eighty-five subjects had their C-IMT, blood lipids and soluble markers measured at baseline, at the 12thmonth 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.

Keywords: Atorvastatin, Coronary artery disease, Intima-media thickness, Soluble markers

Abbreviations: MIAMI, Markers of Inflammation and Atorvastatin effect in previous Myocardial Infarction, CAD, coronary artery disease, ACS, acute coronary syndrome, BP, blood pressure, BMI, body mass index, C-IMT, carotid intima-media thickness, CC-IMT_mean, mean IMT of common carotids, Bif-IMT_mean, mean IMT of bifurcations, ICA-IMT_mean, mean IMT of internal carotid arteries, IMT_mean, mean IMT of the whole carotid tree, IMT_max, max IMT of the whole carotid tree, hs-CRP, high sensitive C-reactive protein, TNF-α, tumor necrosis factor-α, IL, interleukin, sCD40L, soluble CD40 ligand, MMP-9, matrix metalloproteinase-9, TFPI-free, free tissue factor pathway inhibitor, TFPI-total, total tissue factor pathway inhibitor, sICAM-1, soluble intercellular adhesion molecule-1, sVCAM-1, soluble vascular cell adhesion molecule-1, sE-selectin, soluble E-selectin, vWF, von Willebrand factor