Abstract
The intercellular adhesion molecule ICAM-1 mediates adhesion and transmigration of leucocytes to the vascular endothelial wall, a step proposed to be critical in the initiation and progression of atherosclerosis. Whether concentrations of soluble ICAM-1 (sICAM-1) are raised in apparently healthy individuals who later suffer acute myocardial infarction is unknown. We obtained baseline plasma samples from a prospective cohort of 14,916 healthy men enrolled in the Physicians' Health Study. With a nested case-control design, we measured sICAM-1 concentrations for 474 participants who developed a first myocardial infarction, and 474 controls (participants who remained healthy throughout the 9-year follow-up). Cases were matched to controls according to age and smoking status at the time of myocardial infarction. We found a significant association between increasing concentration of sICAM-1 and risk of future myocardial infarction (p = 0.003), especially among participants with baseline sICAM-1 concentrations in the highest quartile (> 260 ng/mL; relative risk 1.6 [95% Cl 1.1-2.4], p = 0.02). This association was present overall as well as among non-smokers, and persisted after control for lipid and non-lipid risk factors. In multivariate analyses, the risk of future myocardial infarction was 80% higher for participants with baseline sICAM-1 concentrations in the highest quartile (relative risk 1.8 [1.1-2.8], p = 0.02). Similar risk estimates were seen among non-smokers. We found slight but significant correlations between sICAM-1 and fibrinogen, high-density-lipoprotein cholesterol, homocysteine, triglycerides, tissue-type plasminogen-activator antigen, and C-relative protein, but adjustment for these altered the risk little. The risk of myocardial infarction associated with raised concentrations of sICAM-1 seemed to increase with length of follow-up. Our data support the hypothesis that cellular mediators of inflammation have a role in atherogenesis and provide a clinical basis to consider antiadhesion therapies as a novel means of cardiovascular disease prevention.
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