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Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure.
J Heart Lung Transplant 2001; 20(3):310-5JH

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) B(12) 500 mcg daily; Stage 2, addition of vit B(6) 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) micromol/liter to 16.3 +/- 6.7 micromol/liter (p < 0.00001), from 17.6 +/- 6.1 micromol/liter to 15.2 +/- 5.3 micromol/liter (p < 0.0001), and from 16.8 +/- 5.2 micromol/liter to 15.6 +/- 5.3 micromol/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 micromol/liter vs 182 +/- 65 micromol/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 B(6) and B(12) 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.

Authors+Show Affiliations

University of British Columbia Heart Transplant Program, St. Paul's Hospital, Vancouver, British Columbia, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11257557

Citation

Cook, R C., et al. "Effective Treatment of Hyperhomocysteinemia in Heart Transplant Recipients With and Without Renal Failure." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 20, no. 3, 2001, pp. 310-5.
Cook RC, Parker S, Kingsbury K, et al. Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure. J Heart Lung Transplant. 2001;20(3):310-5.
Cook, R. C., Parker, S., Kingsbury, K., Frohlich, J. J., Abel, J. G., Gao, M., & Ignaszewski, A. P. (2001). Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 20(3), pp. 310-5.
Cook RC, et al. Effective Treatment of Hyperhomocysteinemia in Heart Transplant Recipients With and Without Renal Failure. J Heart Lung Transplant. 2001;20(3):310-5. PubMed PMID: 11257557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure. AU - Cook,R C, AU - Parker,S, AU - Kingsbury,K, AU - Frohlich,J J, AU - Abel,J G, AU - Gao,M, AU - Ignaszewski,A P, PY - 2001/3/21/pubmed PY - 2001/5/18/medline PY - 2001/3/21/entrez SP - 310 EP - 5 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J. Heart Lung Transplant. VL - 20 IS - 3 N2 - 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) B(12) 500 mcg daily; Stage 2, addition of vit B(6) 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) micromol/liter to 16.3 +/- 6.7 micromol/liter (p < 0.00001), from 17.6 +/- 6.1 micromol/liter to 15.2 +/- 5.3 micromol/liter (p < 0.0001), and from 16.8 +/- 5.2 micromol/liter to 15.6 +/- 5.3 micromol/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 micromol/liter vs 182 +/- 65 micromol/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 B(6) and B(12) 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. SN - 1053-2498 UR - https://www.unboundmedicine.com/medline/citation/11257557/Effective_treatment_of_hyperhomocysteinemia_in_heart_transplant_recipients_with_and_without_renal_failure_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-2498(00)00187-X DB - PRIME DP - Unbound Medicine ER -