Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ridker
P M
PM
Division of Cardiovascular Disease, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. pmridker@bics.bwh.harvard.edu
Hennekens
C H
CH
Roitman-Johnson
B
B
Stampfer
M J
MJ
Allen
J
J
D000975:Antioxidants / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000097:blood / Q000453:epidemiology; D001241:Aspirin / Q000627:therapeutic use; D016022:Case-Control Studies; D004311:Double-Blind Method; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D019207:beta Carotene / Q000627:therapeutic use
D000975:Antioxidants; D010975:Platelet Aggregation Inhibitors; D019207:beta Carotene; D018799:Intercellular Adhesion Molecule-1; D001241:Aspirin