Abstract
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.
Methods
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.
Results
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.
Conclusions
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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References
- Selection and treatment of candidates for heart transplantation.Circulation. 1995; 92: 3593-3612
- Effect of pravastatin on outcomes after cardiac transplantation.N Engl J Med. 1995; 333: 621-627
- The registry of the International Society for Heart and Lung Transplantation.J Heart Lung Transplant. 1998; 17: 656-668
- Syndromes of accelerated atherosclerosis.J Am Coll Cardiol. 1990; 15: 1667-1687
- Causes of late failure after heart transplantation.J Heart Lung Transplant. 1997; 16: 1113-1121
- Homocysteine and coronary artery disease. Clinical evidence and genetic and metabolic background.Arch Intern Med. 1997; 157: 2299-2308
- Plasma homocysteine levels and mortality in patients with coronary artery disease.N Engl J Med. 1997; 337: 230-236
- Hyperhomocysteinaemia in heart transplant recipients.Eur Heart J. 1994; 15: 1191-1195
- Increase in total plasma homocysteine concentration after cardiac transplantation.Mayo Clin Proc. 1995; 70: 125-131
- Hyperhomocysteinemia in cyclosporine-treated renal transplant recipients.Transplantation. 1996; 61: 509-512
- Association of mild hyperhomocysteinemia with cardiac graft vascular disease.Atherosclerosis. 1998; 138: 347-350
Kingsbury KJ, Frohlich JJ, Ignaszewski AP. Evaluation of a treatment algorithm for hyperhomocysteinemia. Can J Cardiol 1998;14(suppl F):96F.
- The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetrahydrofolate reductase genotypes.Arterioscler Thromb Vasc Biol. 1997; 17: 1157-1162
- Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial.Ann Intern Med. 1997; 127: 1089-1092
- The effect of high-dose pyridoxine and folic acid supplementation on serum lipid and plasma homocysteine concentrations in dialysis patients.Clin Nephrol. 1993; 40: 236-240
- High dose B-vitamin treatment of hyperhomocysteinemia in dialysis patients.Kidney Int. 1996; 49: 147-152
- Plasma homocysteine as a risk factor for vascular disease.JAMA. 1997; 277: 1775-1781
- Effect of immunosuppressive therapy, serum creatinine, and time after transplant on plasma total homocysteine in patients following heart transplantation.J Heart Lung Transplant. 1999; 18: 420-424
- Hyperhomocysteinemia and atherosclerotic vascular disease. Pathophysiology, screening, and treatment.Arch Intern Med. 1998; 158: 1301-1306
- Tissue plasminogen activator binding to the annexin II tail domain.J Biol Chem. 1998; 273: 9987-9993
- Concentrations of total homocysteine in plasma in chronic renal failure.Clin Chem. 1990; 36: 2137-2138
- Homocysteine and coronary atherosclerosis.J Am Coll Cardiol. 1996; 27: 517-527
- Net uptake of plasma homocysteine by the rat kidney in vivo.Atherosclerosis. 1995; 116: 59-62
Finkelstein JD. The metabolism of homocysteine: pathways and regulation. Eur J Pediatr 1998;157(Suppl 2):S40–4.
- High homocysteine, low folate, and low vitamin B6 concentrations.Transplantation. 1998; 65: 544-550
- Angiographic trials of lipid-lowering therapy.Br Heart J. 1995; 74: 343
- What targets should lipid-modulating therapy achieve to optimise the prevention of coronary artery disease?.Atherosclerosis. 1997; 131: 1-5
Article info
Publication history
Accepted:
July 26,
2000
Received:
May 5,
2000
Identification
Copyright
© 2001 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
