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What is the role of lipid lowering therapy in heart-allograft failure?
B Reichart1, B M Meiser, K Wenke
1Department of Cardiac Surgery, University of Munich, Grosshadern Medical Center, Germany.
Insights
Long-term cholesterol reduction using Simvastatin significantly decreased graft vessel disease (GVD) after heart transplantation (HTx). The H.E.L.P.-system further reduced LDL cholesterol and prevented or treated GVD in high-risk patients.
Area of Science:
- Cardiology
- Transplantation Immunology
- Lipid Metabolism
Background:
- Hypercholesterolemia is a primary cause of heart disease, often necessitating heart transplantation (HTx).
- Persistent hypercholesterolemia post-HTx accelerates graft vessel disease (GVD) through LDL peroxidation and inflammatory responses.
- Oxidized LDL accumulation in macrophages promotes vascular adhesion molecule expression, contributing to GVD.
Purpose of the Study:
- To evaluate the impact of long-term cholesterol reduction on GVD after heart transplantation.
- To assess the efficacy of Simvastatin and the H.E.L.P.-system in managing hypercholesterolemia and preventing/treating GVD.
Main Methods:
- Prospective open controlled study comparing diet alone (control) versus diet plus Simvastatin.
- One-year angiographies to assess GVD incidence.
- Application of the heparin-mediated extracorporeal low-density lipoprotein precipitation (H.E.L.P.)-system in high-risk patients post-HTx.
Main Results:
- Simvastatin significantly reduced total and LDL-cholesterol without adverse effects.
- GVD incidence was lower in the Simvastatin group (12.1%) compared to the control group (24.1%) at one year.
- The H.E.L.P.-system effectively lowered LDL-cholesterol, Lp(a), and fibrinogen, preventing or treating GVD in high-risk patients.
Conclusions:
- Long-term cholesterol reduction with Simvastatin is effective in decreasing GVD post-heart transplantation.
- The H.E.L.P.-system offers a viable therapeutic option for managing hypercholesterolemia and GVD in high-risk heart transplant recipients.
Abstract:
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.