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


RESULTS
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).


CONCLUSIONS
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.
Labarrere
Carlos A
CA
Methodist Research Institute, Clarian Health Partners, Methodist, Indiana University, Riley Hospitals, Indianapolis, IN 46202, USA. clabarrere@clarian.org
Lee
Joshua B
JB
Nelson
David R
DR
Al-Hassani
Mohammed
M
Miller
Steven J
SJ
Pitts
Douglas E
DE
D001706:Biopsy; D002097:C-Reactive Protein / Q000378:metabolism*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006085:Graft Survival; D016027:Heart Transplantation / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis
D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein