WHAT IS THE ROLE OF LIPID-LOWERING THERAPY IN HEART-ALLOGRAFT FAILURE

Hypercholesterolemia is often the cause for the primary heart disease ultimately necessitating heart transplantation (HTx). After transplant ation, persisting hypercholesterolemia results in an increased peroxid ation of LDL retained by extracellular matrix of the intima. Oxidized LDL accumulates in monocyte derived macrophages, it leads to immobiliz ation of tissue macrophages and provokes the expression of vascular ad hesion molecules, growth factors and cytokines. In a prospective open controlled study, the impact of long-term cholesterol reduction by die t in combination with the HMG-CoA-reductase inhibitor Simvastatin on g raft vessel disease (GVD) was evaluated. Patients of the control group received only a low fat diet. Simvastatin treatment decreased total a nd LDL-cholesterol significantly and was not associated with adverse e ffects. The one year angiographies revealed GVD in 24.1% of the contro l and 12.1% of the Simvastatin group (Study I). In high risk patients with LDL-cholesterol concentrations above 135 mg/dl, in spite of maxim al Simvastatin treatment or plasma fibrinogen concentrations above 400 mg/dl, the heparin mediated extracorporeal low density Lipoprotein pr ecipitation (H.E.L.P.)-system was applied. H.E.L.P. was used either fo r prevention of GVD soon after HTx or for treatment of GVD after devel opment of coronary lesions. Study II proved that the H.E.L.P.-system c ould significantly lower LDL-cholesterol, Lp(a) and fibrinogen in most high risk patients after HTx, resulting in successful prevention or e ven treatment of GVD.