Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial.
BACKGROUND
Cardiac transplantation is associated with oxidant stress, which may contribute to the development of accelerated coronary arteriosclerosis. We postulated that treatment with antioxidant vitamins C and E would retard the progression of transplant-associated arteriosclerosis.


METHODS
In a double-blind prospective study, 40 patients (0-2 years after cardiac transplantation) were randomly assigned vitamin C 500 mg plus vitamin E 400 IU, each twice daily (n=19), or placebo (n=21) for 1 year. The primary endpoint was the change in average intimal index (plaque area divided by vessel area) measured by intravascular ultrasonography (IVUS). Coronary endothelium-dependent vasoreactivity was assessed with intracoronary acetylcholine infusions. IVUS, coronary vasoreactivity, and vitamin C and E plasma concentrations were assessed at baseline and at 1 year follow-up. All patients received pravastatin. Analyses were by intention to treat.


RESULTS
Vitamin C and E concentrations increased in the vitamin group (vitamin C 43 [SD 21] to 103 [43] mmol/L; vitamin E 24 [14] to 65 [27] mmol/L) but did not change in the placebo group (vitamin C 45 [15] vs 43 [16] mmol/L; vitamin E 27 [14] vs 27 [9] mmol/L; p<0.0001 for difference between groups). During 1 year of treatment, the intimal index increased in the placebo group by 8% (SE 2) but did not change significantly in the treatment group (0.8% [1]; p=0.008). Coronary endothelial function remained stable in both groups.


CONCLUSIONS
Supplementation with antioxidant vitamins C and E retards the early progression of transplant-associated coronary arteriosclerosis.
Fang
James C
JC
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA. jfang@partners.org
Kinlay
Scott
S
Beltrame
John
J
Hikiti
Hiroyuki
H
Wainstein
Marco
M
Behrendt
Dominik
D
Suh
Jung
J
Frei
Balz
B
Mudge
Gilbert H
GH
Selwyn
Andrew P
AP
Ganz
Peter
P
D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017539:Tunica Intima / Q000000981:diagnostic imaging; D018084:Ultrasonography, Interventional; D014664:Vasodilation / Q000187:drug effects; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D014810:Vitamin E; D001205:Ascorbic Acid