Value of Serum-Soluble Intercellular Adhesion Molecule-1 for the Noninvasive Risk Assessment of Transplant Coronary Artery Disease, Posttransplant Ischemic Events, and Cardiac Graft Failure

Abstract

Background —Adhesion molecules on arterial endothelium have been implicated in spontaneous atherosclerosis and transplant coronary artery disease (CAD). We studied whether elevated serum-soluble intercellular adhesion molecule-1 (sICAM-1) during the immediate posttransplant period was a risk factor for CAD, posttransplant ischemic events, or cardiac graft failure. Methods and Results —We initially studied serum sICAM-1 in a subset of 16 cardiac allograft recipients (5.5±0.7 samples per patient) to determine a cutoff point that best correlated with presence of arterial and arteriolar endothelial ICAM-1 in matching endomyocardial biopsies. The cutoff value was 308 ng/mL. Subsequently, we prospectively evaluated serum sICAM-1 in serial samples (5.3±0.1 per patient) obtained during the first 3 months after transplantation in a validation subset of 130 recipients and correlated early sICAM-1 levels with long-term outcome. Serum sICAM-1 >308 ng/mL correlated significantly with ICAM-1 on arterial and arteriolar endothelium ( P =0.02). Cardiac allograft recipients with serum sICAM-1 >308 ng/mL had 2.67 (95% CI, 1.28 to 5.59, P =0.009) times greater risk of CAD and 3.63 (95% CI, 1.05 to 12.5, P =0.04) times greater risk of graft failure. Recipients with sICAM-1 >308 ng/mL also developed more severe CAD ( P =0.009) and more ischemic events ( P =0.03) after transplantation. Conclusions —Serum sICAM-1 levels can be used to noninvasively assess risk of transplant CAD, posttransplant ischemic events, and cardiac graft failure.