Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality?

Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule-1 (sICAM-1) concentration and risk of cardiovascular and all-cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM-1 may promote mortality. Six hundred and thirty-one subjects taken from a general population of the middle-aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000. Subjects who died had higher levels of sICAM-1 than those who survived (506(164) vs. 477(162) ng mL(-1), respectively). After adjustment for age, gender and glucose tolerance status, subjects with sICAM-1 levels in the upper quartile (> or =550 ng mL(-1)) had a relative risk of cardiovascular mortality of 2.05 (95% confidence interval, 1.10-3.81) compared to subjects with sICAM-1 levels in the other quartiles. Further adjustment for classical cardiovascular risk factors or indicators of (sub)clinical atherosclerosis, endothelial dysfunction, inflammation and renal function did not materially alter this relative risk. A high sICAM-1 level was more frequent in subjects with type 2 diabetes than in subjects with a normal glucose tolerance (33.3 vs. 17.8%). Individuals with a plasma concentration of sICAM-1 higher than 550 ng mL(-1) had a cardiovascular mortality risk that was twice that of individuals with a lower concentration. Classical cardiovascular risk factors (sub)clinical atherosclerosis, endothelial dysfunction and inflammation do not explain this excess risk.