Background: Elevated total plasma homocysteine (tHcy) levels have been associated with vascular disease and higher mortality in patients with coronary artery disease. Graft coronary disease is a major cause of mortality in long-term survivors of heart transplantation, and hyperhomocysteinemia may be one of its causes. The objectives of our study were to establish the effectiveness of a 3 stage homocysteine-lowering algorithm in a group of 84 heart transplant (HTx) patients and to evaluate the effect of renal function on the response to homocysteine-lowering therapy.
Prospective treatment of 84 Htx patients (64 male; mean age, 48 ± 13 years) with tHcy > 75th percentile consisted of a 3-stage treatment algorithm: Stage 1, folic acid (FA) 2 mg + vitamin (vit) B12 500 mcg daily; Stage 2, addition of vit B6 100 mg daily; Stage 3, increase FA to 15 mg daily. Serum creatinine (Cr) and tHcy levels were measured before treatment and 21 ± 19 weeks after each stage of treatment.
All 3 stages of treatment significantly lowered mean tHcy from 22.4 ± 16.3 (mean ± SD) μmol/liter to 16.3 ± 6.7 μmol/liter (p < 0.00001), from 17.6 ± 6.1 μmol/liter to 15.2 ± 5.3 μmol/liter (p < 0.0001), and from 16.8 ± 5.2 μmol/liter to 15.6 ± 5.3 μmol/liter (p < 0.05), respectively. The average reduction from baseline was 38%. Creatinine levels did not change significantly during the study period. Total plasma homocysteine levels decreased below the 75th percentile in 55% of patients, with Cr levels significantly lower in this group of patients (126 ± 36 μmol/liter vs 182 ± 65 μmol/liter, p < 0.00001). However, we found no significant relationship between % change in tHcy and baseline Cr.
In a group of 84 heart transplant patients with tHcy levels >75th percentile, treatment with FA and vit B6 and B12 according to a 3-stage algorithm resulted in statistically significant declines in mean tHcy levels. Overall, tHcy levels decreased 38%, with target tHcy levels <75th percentile achieved in 55% of the patients. The % change in tHcy was not related to Cr. Further studies are needed to correlate treatment of hyperhomocysteinemia with clinical endpoints, such as the time to development of transplant vasculopathy and long-term survival, and to define the most appropriate targets for therapy.
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Accepted: July 26, 2000
Received: May 5, 2000
© 2001 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.