Relation between soluble intercellular adhesion molecule-1, statin therapy, and long-term risk of clinical cardiovascular events in patients with previous acute coronary syndrome (from PROVE IT-TIMI 22)

Abstract

High levels of adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1), are associated with long-term risk of cardiac events in patients with and without stable coronary artery disease. The relation between sICAM-1 and long-term risk after acute coronary syndromes (ACSs) and the influence of statin treatment has not been explored. Using a nested case-control design, patients with ACS who were enrolled in the PROVE IT-TIMI 22 trial were matched for age, gender, smoking, diabetes, type of ACS presentation, and revascularization for index event (583 patients with recurrent events vs 581 controls). Patients with recurrent events were identified as such by death, myocardial infarction, or hospitalization for recurrent ACS. Soluble ICAM-1 was measured at study entry (approximately 7 days after ACS). After adjusting for statin regimen and other risk factors, patients in quartiles 2 to 4 were at a higher risk of clinical events compared with those in quartile 1 (odds ratio 1.6 for quartile 4 vs 1, 95% confidence interval 1.1 to 2.3, p = 0.02). The risk of adverse events in patients with sICAM-1 levels in quartiles 2 to 4 was most marked in subjects who were allocated to standard dose statin therapy, even after adjusting for low-density lipoprotein cholesterol and C-reactive protein at day 30. The risk in quartiles 2 to 4 was somewhat attenuated in the intensive therapy group. In conclusion, in this large study of patients with ACS, we provide evidence that increased endothelial activation after ACS is independently associated with increased long-term risk of death, myocardial infarction, or recurrent ACS.