Correlation between total homocysteine and cyclosporine concentrations in cardiac transplant recipients

Increased circulating total homocysteine (tHcy) has been implicated as an independent risk factor for atherosclerotic disease. In cardiac transplant patients, accelerated coronary atherosclerosis is an important cause of late allograft failure; however, studies of tHcy in this at-risk group are limited. We sampled a cohort of 72 subjects 3.95+/-3.14 (mean +/- SD) years after transplantation and found that all had tHcy concentrations above our upper reference limit (15.0 micromol/L). The mean tHcy in the transplant group (25.4+/-7.1 micromol/L) was significantly greater than in our reference group (9.0+/-4.3 micromol/L; n = 457; P <0.001). We also examined the effect of age, gender, time since transplant, serum folate and cobalamin, total protein, urate, creatinine, albumin, and trough whole blood cyclosporine concentrations. In a multiple linear regression model, only creatinine (mean 144+/-52 micromol/L; P = 0.021) and trough cyclosporine concentrations (191+/-163 microg/L; P = 0.015) were independent positive predictors of tHcy, whereas serum folate (8.35+/-7.43 nmol/L; P = 0.018) and time since transplant (P = 0.049) were significant negative predictors. We conclude that hyperhomocysteinemia is a common characteristic of cardiac transplant recipients. Our analysis suggests that folate and renal glomerular dysfunction are important contributory factors; however, whole blood cyclosporine concentrations may also predict the degree of hyperhomocysteinemia in this population and therefore influence interpretation of any apparent response to treatment.