The determinants of elevated total plasma cholesterol levels in cardiac transplant recipients administered low dose cyclosporine for immunosuppression

Abstract

Elevated total plasma cholesterol level is a frequent finding after cardiac transplantation. To identify risk factors for the development of hypercholesterolemic states, we applied multivariate statistics in a logistic and linear manner. Six-month posttransplantation levels of total plasma cholesterol in 57 adult heart recipients were available for analysis. Maintenance immunosuppression was carried out with either cyclosporine and azathioprine or both agents plus low-dose steroids. Total plasma cholesterol levels were dichotomized for the logistic analysis (1) by the age- and sex-matched 75th and 90th percentiles of a reference population according to National Institutes of Health treatment guidelines and (2) by the cut point 250 mg/dl. Twelve potential risk factors were evaluated as covariates: recipient age, body weight after 6 months, body weight gain over 6 months, body mass index after 6 months, body mass index gain over 6 months, current cyclosporine dosage, trough level of cyclosporine in whole blood according to high-performance liquid chromatography after 6 months, cumulative cyclosporine dosage over 6 months, serum bilirubin, type of original cardiac disease, maintenance steroids, and steroid bolus treatment. Multivariate logistic regression yielded the type of original cardiac disease as a significant predictor of posttransplantation hypercholesterolemia exceeding the 90th percentile (p = 0.019) and of hypercholesterolemia exceeding 250 mg/dl (p = 0.032). Maintenance steroids were identified as a second significant cofactor (p = 0.069) for total plasma cholesterol levels exceeding 250 mg/dl. Multiple linear regression again revealed the type of original cardiac disease and maintenance steroids as significant predictors by p values of 0.005 and 0.013, respectively. Patients with coronary artery disease as the original cardiac pathology and low-dose maintenance steroids had the greatest risk for the development of elevated total plasma cholesterol levels after cardiac transplantation. However, the overall predictive quality of the linear model was limited (multiple r value 0.43), which indicates that other variables besides the tested ones attributed to elevated total plasma cholesterol levels. These results confirm the adverse role of maintenance steroids on posttransplantation hypercholesterolemia and demonstrate the type of original cardiac disease as the most important risk factor. They suggest that abnormalities of lipoprotein metabolism and dietary factors continue to affect total plasma cholesterol levels after cardiac transplantation.