Impact of coronary endothelial function on the progression of cardiac transplant-associated arteriosclerosis: effect of anti-oxidant vitamins C and E.
BACKGROUND
Excessive vascular oxidant stress has been implicated in cardiac transplant-associated arteriosclerosis (TxAA). In a recent placebo-controlled study of 40 cardiac transplant recipients, vitamin C 500 mg twice a day and vitamin E 400 IU twice a day for 1 year retarded the progression of TxAA, as assessed by intravascular ultrasound (IVUS). Endothelial dysfunction is a key feature of TxAA and reflects oxidant stress. We hypothesized that coronary endothelial dysfunction portends greater TxAA progression and a larger therapeutic response to anti-oxidant vitamins.


METHODS
In this pre-specified analysis, the 40 cardiac transplant recipients were categorized according to normal or abnormal coronary endothelial vasomotor function at baseline, as assessed by acetylcholine (10(-8) to 10(-6) mol/liter). The effect of anti-oxidant vitamins within these two groups of patients was assessed by the change in intimal index over 1 year using IVUS.


RESULTS
With placebo (n = 21), the increase in intimal index was greater in the presence vs absence of endothelial dysfunction (11 +/- 3% vs 5 +/- 1%, p < 0.05). Among patients with endothelial dysfunction (n = 21), the intimal index increased 11 +/- 3% with placebo, but decreased -1 +/- 2% with vitamins (p = 0.002). Among patients with normal endothelial function (n = 14), the intimal index increased 5 +/- 1% with placebo and 1 +/- 1% with vitamins (p < 0.05).


CONCLUSIONS
Endothelial dysfunction indicates rapid TxAA progression, even in the statin era. Although anti-oxidant vitamins reduce disease progression in patients with normal or abnormal endothelial function, the magnitude of benefit is larger in patients with endothelial dysfunction.
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Dominik
D
Behrendt
John
J
Beltrame
Hiro
H
Hikiti
Marco
M
Wainstein
Scott
S
Kinlay
Andrew P
AP
Selwyn
Peter
P
Ganz
James C
JC
Fang
D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006439:Hemodynamics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D018084:Ultrasonography, Interventional; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D002317:Cardiovascular Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D014810:Vitamin E; D001205:Ascorbic Acid