During this presentation Dr. Labarrere discusses the role of CRP as a risk marker for cardiac allograft vasculopathy following human heart transplantation.

The development of transplant-associated atherosclerosis is commonly associated with allograft loss or patient death. In a prospective study of 121 cardiac transplant recipients, it was found that fibrin in endomyocardial biopsies during the first month after transplantation was able to identify patients at high risk for developing coronary artery disease or graft failure (1). Fibrin can become deposited in the allograft through different mechanisms including endothelial activation. This in turn is indicated by an upregulation of intercellular adhesion molecule-1 (ICAM-1). Arterial endothelial ICAM-1 expression and soluble ICAM-1 early after transplantation have been associated with the development of coronary artery disease (2,3).

C-reactive protein is known to stimulate ICAM-1, and in a prospective study of 109 heart transplant patients, CRP levels were significantly related to arterial endothelial ICAM-1 expression in endomyocardial biopsy samples, and soluble ICAM-1 concentrations. Further, those with early raised CRP levels were at higher risk for coronary artery disease and graft failure (4).

Fibrin deposition in the allografts can also occur due to failure of the anticoagulant and fibrinolytic pathways, indicated by a loss of antithrombin binding in the microvasculature, and a loss of tissue plasminogen activator (tPA) respectively. Dr. Labarrere shows further data from heart transplant patients relating CRP levels to IL-6 levels, to a loss of microvascular antithrombin, and to depleted arteriolar tPA; as well as patient outcomes based on these parameters.

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After viewing this presentation the participant will be able to discuss:

- The significance and mechanisms of fibrin deposition in the allograft after heart transplantation
- The role of CRP as a risk marker for allograft vasculopathy after heart transplantation

1. Carlos A. Labarrere MD, David R. Nelson MS and W. Page Faulk MD. Myocardial fibrin deposits in the first month after transplantation predict subsequent coronary artery disease and graft failure in cardiac allograft recipients The American Journal of Medicine.Volume 105, Issue 3 , September 1998, Pages 207-213.

2. C. A. Labarrere, D. R. Nelson and W. P. Faulk. Endothelial activation and development of coronary artery disease in transplanted human hearts JAMA. 1997;278:1169-1175.

3. Carlos A. Labarrere, MD; David R. Nelson, MS; Steven J. Miller, PhD; Jennifer M. Nieto, BS; Jennifer A. Conner, BS; Douglas E. Pitts, MD; Philip C. Kirlin, MD; Harold G. Halbrook, MD. Value of Serum-Soluble Intercellular Adhesion Molecule-1 for the Noninvasive Risk Assessment of Transplant Coronary Artery Disease, Posttransplant Ischemic Events, and Cardiac Graft Failure Circulation. 2000;102:1549.

4. DrCarlos A Labarrere MD, Joshua B Lee BS, David R Nelson MS, Mohammed Al-Hassani MD, Steven J Miller PhD and Douglas E Pitts MDC-reactive protein, arterial endothelial activation, and development of transplant coronary artery disease: a prospective study The Lancet.Volume 360, Issue 9344 , 9 November 2002, Pages 1462-1467.