Strategies for minimizing hyperlipidemia after cardiac transplantation.
Allograft coronary artery disease represents a major limitation to long-term survival after cardiac transplantation. Hyperlipidemias have been linked to the development of native coronary atherosclerosis, and hyperlipidemic states have correlated with the severity of allograft coronary artery disease. Heart transplant recipients typically manifest increases in plasma levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglycerides within the first 3-12 months following transplantation. Factors known to promote post-transplant hyperlipidemia include the use of corticosteroids, cyclosporine (interference with clearance and increased oxidizability of LDL), sirolimus (hypertriglyceridemia), and patient-specific causes of hyperlipidemia which contributed to their underlying heart disease. Hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors are the foundation of antilipid therapy following cardiac transplantation. Pravastatin is effective in lowering plasma cholesterol levels and is associated with a decreased incidence and progression of allograft coronary artery disease. All HMG-CoA reductase inhibitors except pravastatin are metabolized by the hepatic cytochrome P450 system which metabolizes cyclosporine, increasing the risk of myostitis when they are used in large dosages with cyclosporine. Simvastatin, atorvastatin and fluvastatin have been studied in heart transplant recipients. Gemfibrozil has proved effective in transplant recipients when there is isolated marked elevation of plasma triglyceride levels. When hyperlipidemia persists despite therapy, some benefit may result with conversion from cyclosporine to tacrolimus. Although a definitive link between hyperlipidemia and allograft coronary disease has yet to be proven, available evidence points to abnormal lipid metabolism as part of the complex etiologic machinery driving the process of 'chronic rejection'. Consensus exists within the transplant community that a HMG-CoA reductase inhibitor such as pravastatin, should be part of the routine post-transplant drug regimen, and persistent hyperlipidemia should be aggressively treated.
Kirklin
James K
JK
Department of Surgery, Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. jkirklin@uab.edu
Benza
Raymond L
RL
Rayburn
Barry K
BK
McGiffin
David C
DC
D002791:Cholesterol, Dietary / Q000009:adverse effects; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000209:etiology / Q000517:prevention & control; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D014184:Transplantation, Homologous / Q000473:pathology
D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D007166:Immunosuppressive Agents