Effect of immunosuppressive therapy, serum creatinine, and time after transplant on plasma total homocysteine in patients following heart transplantation

Objectives: To determine the prevalence of hyperhomocysteinemia in heart transplant recipients, and to assess the effect of renal function and immunosuppressive medication on total plasma homocysteine (tHcy) levels. Background: Elevated plasma tHcy levels have been associated with increased risk of mortality in patients with established coronary artery disease. Graft coronary disease is the major cause of morbidity and mortality in long-term survivors of heart transplantation. The tHcy has been found to be elevated in heart and kidney transplant patients, however, the etiologic factors have not been clearly delineated. Methods: The study group consisted of 70 heart transplant recipients (56 males, 14 females, mean age 53 +/- 13 years range 17 to 69 years). The parameters evaluated were fasting tHcy level, cumulative cyclosporine (CyA) dose, cumulative prednisone dose, serum creatinine, and time from transplantation. Results: The mean fasting tHcy level was 20.5 +/- 10.2 mu mol/L (range 5.2 to 59.0 mu mol/L). Sixty-one (87%) had fasting tHcy levels greater than the seventy-fifth percentile of the general population (> 12.2 mu mol/L in males, and > 10.1 mu mol/L in females). There was no difference in mean post-transplant tHcy level between patients with and without coronary artery disease before transplantation (21.0 +/- 11.4 vs 19.3 +/- 6.7 mu mol/L, p = NS). There were significant relationships between the tHcy level and the serum creatinine (r = 0.76, p < 0.001), and cumulative exposure to CyA (r = 0.31, p < 0.01). There were no significant relationships between tHcy levels and cumulative prednisone dose, or time from transplantation. Conclusions: Fasting tHcy levels are markedly elevated in the majority of patients following heart transplantation, and are correlated to serum creatinine. Further studies are needed to determine other etiologic factors of elevated tHcy following heart transplantation, and to examine the impact of elevated tHcy on clinical outcomes. J Heart Lung Transplant 1999;18:420-424.