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Frequency of hypercholesterolemia after cardiac transplantation
J S Stamler1, D E Vaughan, M A Rudd
1Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Insights
Cyclosporin A may worsen cardiac transplant atherosclerosis by affecting cholesterol levels. This immunosuppressant drug can lead to an atherogenic lipoprotein profile, increasing the risk of arterial disease in transplant recipients.
Area of Science:
- Cardiology
- Immunology
- Transplantation Medicine
Background:
- Cardiac transplant recipients often develop accelerated coronary atherosclerosis.
- The exact mechanisms driving this process remain unclear, but immune-mediated arterial injury is suspected.
- Cyclosporin A, a potent immunosuppressant, does not fully prevent this accelerated atherosclerosis.
Purpose of the Study:
- To investigate the hypothesis that cyclosporin A contributes to accelerated atherosclerosis in cardiac transplant patients.
- To explore whether cyclosporin A's potential hepatotoxicity impairs hepatic clearance of low-density lipoprotein (LDL).
- To determine if this impairment results in a more atherogenic lipoprotein profile.
Main Methods:
- Serum cholesterol levels were analyzed in cardiac transplant patients post-transplantation.
- Measurements included total cholesterol and the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol.
- These levels were tracked progressively after transplantation.
Main Results:
- A significant and progressive increase in total cholesterol was observed.
- The ratio of total cholesterol to HDL cholesterol also showed a significant and progressive increase.
- These findings indicate the development of an atherogenic lipoprotein profile.
Conclusions:
- Cyclosporin A treatment in cardiac transplant patients is associated with an atherogenic lipoprotein profile.
- This altered lipid profile, characterized by increased total cholesterol and a higher total-to-HDL cholesterol ratio, may contribute to accelerated atherosclerosis.
- Further research is warranted to elucidate the precise role of cyclosporin A's hepatotoxicity in this process.
Abstract:
Cardiac transplant patients are prone to accelerated coronary atherosclerosis. The mechanism by which this process occurs is not yet known, although immunologically mediated arterial injury is thought to play a primary role in its pathogenesis. Despite immunosuppressive potency, patients treated with cyclosporin A remain at significant risk for the development of accelerated atherosclerosis. It is hypothesized that cyclosporin A's hepatotoxic effects might contribute to the atherosclerotic process by impairing low density lipoprotein hepatic clearance in transplant patients, which would be reflected in a more atherogenic lipoprotein profile. To test this hypothesis, serum cholesterol levels were analyzed after transplantation. Significant and progressive increases in total cholesterol and in the total-to-high density lipoprotein cholesterol ratio were found. This atherogenic lipoprotein profile may contribute to accelerated atherosclerosis in cardiac transplant patients treated with cyclosporin A.