A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease.
OBJECTIVE
This study was designed to determine the effects of folic acid therapy on endothelial function in patients with coronary artery disease (CAD).


BACKGROUND
Hyperhomocysteinemia, a risk factor for CAD, may cause atherosderosis by oxidative endothelial injury. Folic acid reduces plasma homocysteine, but the effect on adverse vascular events is unknown.


METHODS
In a double-blind placebo-controlled trial, 90 patients (mean age [range] 63 [46 to 79] years, 79 men) with CAD were randomized to either folic acid 5 mg or placebo daily for 12 weeks. Endothelial function was assessed by measuring: 1) flow-mediated endothelium-dependent dilation (EDD) of the brachial artery; 2) combined serum nitrite/nitrate (NOx) concentrations and; 3) plasma von Willebrand factor (vWF) concentration.


RESULTS
At the end of the study, plasma homocysteine was lower in the folic acid group compared with the placebo group (mean [95% confidence interval] 9.3 (8.5 to 10.1) vs. 12.3 [11.3 to 13.4] micromol/l, p < 0.001). Although there were no significant differences in EDD, serum NOx or plasma vWF between the two groups, there was a greater increase in EDD from baseline in the folic acid group compared to placebo (1.2 [0.7 to 1.8] vs. 0.4 [-0.3 to 1.1]%, p = 0.07).


CONCLUSIONS
Folic acid reduced plasma homocysteine and was associated with a trend toward improved endothelial function in patients with CAD. The absence of an unequivocally positive result may have been due to inadequate sample size or chance. This reinforces the need for the results of large randomized controlled trials before the implementation of routine folic acid supplementation.
Thambyrajah
J
J
Division of Medical Sciences (Cardiology), University of Birmingham, United Kingdom. jeet@thambyrajah.freeserve.co.uk
Landray
M J
MJ
Jones
H J
HJ
McGlynn
F J
FJ
Wheeler
D C
DC
Townend
J N
JN
D000368:Aged; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D012039:Regional Blood Flow; D014841:von Willebrand Factor / Q000032:analysis
D009566:Nitrates; D009573:Nitrites; D014841:von Willebrand Factor; D006710:Homocysteine; D005492:Folic Acid