title: Homocysteine-lowering therapy and early progression of transplant vasculopathy: a prospective, randomized, IVUS-based study.
abstract: 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.
authors.affiliation: Institute of Cardiology, University of Bologna, Academic Hospital, S. Orsola-Malpighi, Italy. lpotena@cvmed.stanford.edu
authors.forename: Luciano
authors.initials: L
authors.lastname: Potena
authors.forename: Francesco
authors.initials: F
authors.lastname: Grigioni
authors.forename: Gaia
authors.initials: G
authors.lastname: Magnani
authors.forename: Paolo
authors.initials: P
authors.lastname: Ortolani
authors.forename: Fabio
authors.initials: F
authors.lastname: Coccolo
authors.forename: Simonetta
authors.initials: S
authors.lastname: Sassi
authors.forename: Koen
authors.initials: K
authors.lastname: Kessels
authors.forename: Koen
authors.initials: K
authors.lastname: Koessels
authors.forename: Cinzia
authors.initials: C
authors.lastname: Marrozzini
authors.forename: Antonio
authors.initials: A
authors.lastname: Marzocchi
authors.forename: Samuela
authors.initials: S
authors.lastname: Carigi
authors.forename: Anna C
authors.initials: AC
authors.lastname: Musuraca
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Carlo
authors.initials: C
authors.lastname: Magelli
authors.forename: Angelo
authors.initials: A
authors.lastname: Branzi
mesh_terms: 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*
chemical_list: D013763:Tetrahydrofolates; D006710:Homocysteine; D005492:Folic Acid; C005984:5-methyltetrahydrofolate