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 transplantation, persisting hypercholesterolemia results in an increased peroxidation of LDL retained by extracellular matrix of the intima. Oxidized LDL accumulates in monocyte derived macrophages, it leads to immobilization of tissue macrophages and provokes the expression of vascular adhesion molecules, growth factors and cytokines. In a prospective open controlled study, the impact of long-term cholesterol reduction by diet in combination with the HMG-CoA-reductase inhibitor Simvastatin on graft vessel disease (GVD) was evaluated. Patients of the control group received only a low fat diet. Simvastatin treatment decreased total and LDL-cholesterol significantly and was not associated with adverse effects. The one year angiographies revealed GVD in 24.1% of the control and 12.1% of the Simvastatin group (Study I). In high risk patients with LDL-cholesterol concentrations above 135 mg/dl, in spite of maximal Simvastatin treatment or plasma fibrinogen concentrations above 400 mg/dl, the heparin mediated extracorporeal low density lipoprotein precipitation (H.E.L.P.)-system was applied. H.E.L.P. was used either for prevention of GVD soon after HTx or for treatment of GVD after development of coronary lesions. Study II proved that the H.E.L.P.-system could significantly lower LDL-cholesterol, Lp(a) and fibrinogen in most high risk patients after HTx, resulting in successful prevention or even treatment of GVD.
Reichart
B
B
Department of Cardiac Surgery, University of Munich, Grosshadern Medical Center, Germany.
Meiser
B M
BM
Wenke
K
K
Brandl
U
U
Seidel
D
D
Thiery
J
J
D017023:Coronary Angiography; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000000981:diagnostic imaging / Q000378:metabolism / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D019821:Simvastatin; D014184:Transplantation, Homologous
D000960:Hypolipidemic Agents; D008055:Lipids; D008148:Lovastatin; D019821:Simvastatin