C-reactive protein, arterial endothelial activation, and development of transplant coronary artery disease: a prospective study

Abstract

Background: Arterial endothelial expression and raised serum concentrations of the soluble form of intercellular adhesion molecule-1 (ICAM-1) are implicated in development of transplant coronary artery disease. We investigated whether C-reactive protein, known to stimulate ICAM-1, was associated with increased ICAM-1 concentration and subsequent development of coronary artery disease.

Methods: With sandwich ELISAs, we measured C-reactive protein and soluble ICAM-1 in serial serum samples obtained during the first 3 months after transplantation in 109 heart-transplant patients. Matching endomyocardial biopsy samples were screened immunohistochemically for arterial endothelial ICAM-1. Serial coronary angiograms were assessed for development, severity, and progression of coronary artery disease.

Findings: We showed a significant correlation (p=0.001) between raised concentrations of C-reactive protein and arterial endothelial ICAM-1 expression in endomyocardial biopsy samples. We also noted a significant relation between C-reactive protein and soluble ICAM-1 concentrations soon after transplantation (p=0.003). Early raised C-reactive protein concentrations were associated with development (p=0.004), increased severity (p=0.02), and enhanced rate of progression (p=0.01) of coronary artery disease, and with heightened frequency of ischaemic events (p=0.049) and graft failure (p=0.04).

Interpretation: C-reactive protein concentration can be used to identify heart-transplant patients at increased risk of coronary artery disease and graft failure. Treatments directed at reduction of C-reactive protein concentration could improve patients' outcome.