Lipid peroxides and antioxidant defenses in accelerated transplantation-associated coronary arteriosclerosis

Accelerated coronary artery disease develops in most if not all heart transplant recipients within the first year after transplantation. Increased lipid peroxidation seems to be involved in atherogenesis. In these patients we have investigated whether there is an association between lipid peroxidation, reduced antioxidant defenses, and some conventional coronary risk factors. Lipid peroxides, lipids, uric acid, albumin, antioxidant enzymes and their cofactors (the trace elements selenium, iron, copper, and zinc) have been determined in heart transplant recipients compared with nonrecipients with coronary artery disease. Lipid peroxides (p = 0.002) and uric acid (p = 0.01) were higher and zinc (p = 0.001) was lower in heart transplant recipients. Thirteen of 30 transplant recipients compared with one of 30 nonrecipients (p < 0.001) had very low (less than 10 mumol/L) zinc levels. Antioxidant enzymes and other trace elements were not significantly different. In univariate regression analysis, zinc correlated positively with albumin (p = 0.02) and negatively with lipid peroxides (p < 0.05). Uricemia had a strongly positive correlation with hydroperoxides (r = 0.45; p = 0.0001). In stepwise multivariate regression analysis, lipids, uricemia, creatinine, and zinc were significant (p < or = 0.004) predictors of the lipid peroxide level. Cyclosporine and corticosteroid dosages were significant (p = 0.01) determinants of zinc concentration in the transplant recipients. Although a causal relationship between increased lipid peroxidation and accelerated arteriosclerosis is not definitely demonstrated, the results of this analysis suggest new insights into conventional coronary disease risk factors and possible therapeutic interventions; further controlled trials are needed.