Homocysteine-lowering therapy and early progression of transplant vasculopathy: a prospective, randomized, IVUS-based study.
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.
Potena
Luciano
L
Institute of Cardiology, University of Bologna, Academic Hospital, S. Orsola-Malpighi, Italy. lpotena@cvmed.stanford.edu
Grigioni
Francesco
F
Magnani
Gaia
G
Ortolani
Paolo
P
Coccolo
Fabio
F
Sassi
Simonetta
S
Kessels
Koen
K
Koessels
Koen
K
Marrozzini
Cinzia
C
Marzocchi
Antonio
A
Carigi
Samuela
S
Musuraca
Anna C
AC
Russo
Antonio
A
Magelli
Carlo
C
Branzi
Angelo
A
D000328:Adult; D003586:Cytomegalovirus Infections; D018450:Disease Progression; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia; D006965:Hyperplasia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012107:Research Design; D012307:Risk Factors; D013763:Tetrahydrofolates / Q000627:therapeutic use; D013997:Time Factors; D014463:Ultrasonography; D014652:Vascular Diseases / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology*
D013763:Tetrahydrofolates; D006710:Homocysteine; D005492:Folic Acid; C005984:5-methyltetrahydrofolate