Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure

Cook, R.C.M.; Parker, Stephen; Kingsbury, Kori; Fröhlich, Jiří; Abel, James G.; Gao, Min; Ignaszewski, Andrew

doi:10.1016/s1053-2498(00)00187-x

Cited by 8 publications

(3 citation statements)

References 23 publications

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“…Therefore, therapies reducing the impact of risk factors acting early after HT may have significant efficacy in increasing long-term survival (36). Among the many risk factors of potential interest for therapeutic interventions, hyperhomocysteinemia has been reported to be an important contributor to CAV development (7)(8)(9)(10), and it may be easily corrected by adequate supplementation with folic acid (6,10,16,17). However, randomized studies investigating the impact of homocysteine lowering on CAV progression are lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Homocysteine is a thiolcontaining intermediate of the methionine metabolic pathway, and its plasma concentrations are mainly dependent upon renal function, genetic background and dietary intake of folic acid and B-group vitamins (6,14,15). Increased cardiovascular risk due to hyperhomocysteinemia is potentially easily reversible, since intake of adequate amount of folic acid has been found to reduce tHcy concentration both in the general population and in HT recipients (6,10,16,17). However, no prospective studies about the effect of folate intake for CAV prevention are available (18).…”

Section: Introductionmentioning

confidence: 99%

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Homocysteine‐Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS‐Based Study

Potena

Grigioni

Magnani

et al. 2005

American Journal of Transplantation

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Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n = 22), or standard therapy (control group, n = 22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p < 0.001), coronary intimal area increased similarly in the two groups (p > 0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p < 0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n = 19; p = 0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p = 0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia.Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Homocysteine‐Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS‐Based Study

Potena

Grigioni

Magnani

et al. 2005

American Journal of Transplantation

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“…Hyperhomocysteinemia was reported to be a risk factor for CAV progression (80) but did not correlate with vascular complications/death in another study (81). While folic acid supplementation is able to reverse hyperhomocysteinemia in heart transplant patients (82,83), it is not known if there is a favorable influence on CAV.…”

Section: Prevention Of Cavmentioning

confidence: 99%

Contemporary Concepts in Prevention and Treatment of Cardiac Allograft Vasculopathy

Mehra

2006

American Journal of Transplantation

120

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Cardiac allograft vasculopathy (CAV), is characterized by heterogeneous proliferative thickening of the vascular intima of the cardiac allograft vasculature. Since its presentation is commonly clinically silent, early diagnosis and preventative therapy are critical. Preventative therapy including optimization of immunosuppressive therapy and treatment of comorbidities associated with CAV progression must be initiated early since most of the intimal thickening occurs during the first year posttransplant. Longterm use of calcineurin inhibitors is associated with a high incidence of chronic renal disease and also contributes to hyperlipidemia and hypertension, all of which may exacerbate CAV. In addition, statins, antihypertensive agents and anti-CMV agents all have demonstrated benefits in reducing CAV. Once established, the limited treatment options include nonpharmacologic interventions such as retransplantation, percutaneous coronary interventions, coronary artery bypass grafting, transmyocardial laser revascularization and heparin-induced/mediated extracorporeal LDL plasmapheresis (HELP). As the use of new assessment tools increases our understanding of this disease, better preventative and treatment strategies are evolving.

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Hyperhomocysteinemia in patients with symptomatic chronic heart failure: Prevalence and prognostic importance—pilot study

Naruszewicz¹,

Jankowska²,

Zymliński³

et al. 2007

Atherosclerosis

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Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure

Cited by 8 publications

References 23 publications

Homocysteine‐Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS‐Based Study

Homocysteine‐Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS‐Based Study

Contemporary Concepts in Prevention and Treatment of Cardiac Allograft Vasculopathy

Hyperhomocysteinemia in patients with symptomatic chronic heart failure: Prevalence and prognostic importance—pilot study

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