Effective treatment of hyperhomocysteinemia in heart transplant recipientswith and without renal failure

Background: Elevated total plasma homocysteine (tHcy) levels have been asso ciated with vascular disease and higher mortality in patients with coronary artery disease. Graft coronary disease is a major cause of mortality in lo ng-term survivors of heart transplantation, and hyperhomocysteinemia may be one of its causes. The objectives of our study were to establish the effec tiveness of a 3 stage homocysteine-lowering algorithm in a group of 84 hear t transplant (HTx) patients and to evaluate the effect of renal function on the response to homocysteine-lowering therapy. Methods: Prospective treatment of 84 Htx patients (64 male: mean age, 48 +/ - 13 years) with tHcy > 75th percentile consisted of a 3-stage treatment al gorithm: Stage 1, folic acid (FA) 2 mg + vitamin (vit) B-12 500 mcg daily; Stage 2, addition of vit B-6 100 mg daily; Stage 3, increase FA to 15 mg da ily. Serum creatinine (Cr) and tHcy levels were measured before treatment a nd 21 +/- 19 weeks after each stage of treatment. Results: All 3 stages of treatment significantly lowered mean tHcy from 22. 4 +/- 16.3 (mean +/- SD) mu mol/liter to 16.3 +/- 6.7 mu mol/liter (p < 0.0 0001), from 17.6 +/- 6.1 <mu>mol/liter to 15.2 +/- 5.3 mu mol/liter (p < 0. 0001), and from 16.8 +/- 5.2 <mu>mol/liter to 15.6 +/- 5.3 mu mol/liter (p < 0.05), respectively. The average reduction from baseline was 38%. Creatin ine levels did not change significantly during the study period. Total plas ma homocysteine levels decreased below the 75th percentile in 55% of patien ts, with Cr levels significantly lower in this group of patients (126 +/- 3 6 <mu>mol/liter vs 182 +/- 65 mu mol/liter, p < 0.00001). However, we found no significant relationship between % change in tHcy and baseline Cr. Conclusions: In a group of 84 heart transplant patients with tHcy levels >7 5th percentile, treatment with FA and vit B-6 and B-12 according to a 3-sta ge algorithm resulted in statistically significant declines in mean tHcy le vels. Overall, tHcy levels decreased 38%, with target tHcy levels <75th per centile achieved in 55% of the patients. The % change in tHcy was not relat ed to Cr. Further studies are needed to correlate treatment of hyperhomocys teinemia with clinical endpoints, such as the time to development of transp lant vasculopathy and long-term survival, and to define the most appropriat e targets for therapy.