Differential effect of soluble intercellular adhesion molecule-1 on the progression of atherosclerosis as compared to arterial thrombosis: a prospective analysis of the Women's Health Study.

BACKGROUND: Soluble intercellular adhesion molecule-1 (sICAM-1) is a transmembrane protein involved in the migration and adhesion of leukocytes to the vascular endothelium. While some studies indicate that elevated baseline sICAM-1 levels predict cardiovascular events, most of these studies were done in men; moreover, uncertainty exists regarding whether sICAM-1 levels predict vascular events consistent with acute thrombosis versus atherosclerotic disease progression. METHODS AND RESULTS: In this prospective evaluation of 23,984 apparently healthy women, we measured sICAM-1 levels and followed participants for the development of cardiovascular (CVD) endpoints typically associated with atherosclerotic disease progression with resultant vessel narrowing (percutaneous transluminal angioplasty and coronary artery bypass grafting) and endpoints typically associated with vascular thrombosis and vessel occlusion (myocardial infarction (MI), ischemic stroke and death from a coronary cause). During a mean follow-up of 10 years, there were 741 events. For vascular events indicative of coronary atherosclerotic disease progression with luminal narrowing, Cox-proportional hazards models revealed an increase in vascular event rates from the lowest to highest quintile of baseline sICAM-1 after adjustment for CVD risk factors [hazard ratios (HR): 1.0, 1.4, 1.1, 1.6, 1.6, p(trend)=0.008]. By contrast, for endpoints reflective of acute vessel thrombosis, we found no association with sICAM-1 levels [HR for myocardial infarction: 1.0, 1.2, 0.9, 1.2, 1.0, p(trend)=0.7; HR for stroke (CVA): 1.0, 0.9, 1.0, 1.0, 1.1, p(trend)=0.6; HR for cardiovascular death: 1.0, 0.9, 0.7, 0.7, 0.8, p(trend)=0.7] except among smokers (RR=1.0, 1.4, 2.8, 3.8, 3.7, p=0.007). CONCLUSIONS: Among women without a history of cardiovascular disease, sICAM-1 levels are predictive of CVD events that reflect coronary atherosclerotic disease progression and vessel narrowing, but not those events associated with acute thrombosis/vessel occlusion.