An increased risk of myocardial infarction in subjects with concentrations of C-reactive protein in the upper end of the normal range1-3 suggested the possibilities better risk assessment by measurement of other, more specific, markers of inflammation. Ridker et al.4 demonstrated that subjects with plasma levels of soluble Intercellular Adhesion Molecule-1 (sICAM-1) in the top quartile of normal had an 80% higher risk of developing a myocardial infarct. Similarly, Labarrere et al.5 showed that endothelial expression of ICAM-1 and HLA-DR in arteries of allografted hearts was predictive of subsequent coronary heart disease and increased graft failure.
ICAM-1 is expressed by endothelial cells in response to inflammatory cytokines. It participates in the adhesion of neutrophils to the endothelium, an essential step in the extravasation of neutrophils at the site of inflammation. Surface-expressed ICAM-1 is shed from the cell and circulates as sICAM-1. Plasma levels of sICAM-1 are elevated in immune diseases, including graft vs. host disease.
Ridker et al.4 used plasma samples and data from the Physicians' Health Study. This study, in which healthy physicians gave baseline blood samples and complete medical information, began in 1982 and has followed the medical histories of the subjects. Concentrations of sICAM-1 were measured in baseline plasma samples from 474 subjects who subsequently had a myocardial infarction and 474 matched controls who have not yet had an infarct.
A level of sICAM-1 in the highest quartile of baseline values had a relative risk factor of 1.6 for a subsequent infarct. The risk associated with high levels of sICAM-1 was independent of other risk factors. The risk was greater with increasing time to infarct; there was no added risk for a myocardial infarct within one year but a relative risk factor of 2 for a myocardial infarct in 4-8 years.
Labarrere et al.5 studied subjects who had heart transplants in which there were pre-transplant and serial post-transplant endocardial biopsy specimens, which they used for immunohistochemical analysis of the expression of ICAM-1 and HLA-DR antigens on endothelial cells. Of 121 pre-transplant hearts, none showed expression of these antigens, but during the first 3-month post-transplant period, positive results were obtained in differing percentages of biopsy specimens. The higher the percentage of "positive" biopsies, the greater the probability of coronary artery disease and of graft failure.
- Haverkate, F. et al. (1997) Lancet 349:462.
- Ridker, P.M. et al. (1997) New Engl. J. Med. 336:973.
- Cytokine Bulletin, Spring, 1997, page 11, R&D Systems.
- Ridker, P.M. et al. (1998) Lancet 351:88.
- Labarrere, C.A. (1997) JAMA 278:1169.