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 - 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
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.
Does folic acid therapy improve endothelial function in patients with coronary artery disease (CAD)?
Patients Enrolled: 86
Mean Patient Age: 46-79
A double-blind placebo-controlled trial of 5mg of folic acid administered for 3 months in 86 patients with CAD was performed. Endothelial function was assessed by measuring the change in brachial artery diameter with ultrasound following occlusion release, plasma von Willebrand factor (vWF) and the ratio of nitrite/nitrate concentration considered the metabolic end products of endothelial-derived nitric oxide.
There was no difference between groups for mean age (63 years, range 46–79 years), men (85%), smokers (10%), baseline homocysteine level (11.7 μmol/L, range 10.6–12.7 μmol/L), blood pressure, lipids and renal function. The pretreatment endothelial-dependent dilation (EDD) averaged 3.3% (range 2.2–4.3%) in the folic acid group and did not differ from placebo. The homocysteine level decreased after treatment (mean 9.3 μmol/L folic acid vs. 12.3 μmol/L placebo), but there was no significant change in vWF, nitrite/nitrate or EDD.
Folic acid reduced the homocysteine levels and was associated with a trend toward improvement in endothelial function by flow-mediated dilation.
In so far as homocysteine is associated with endothelial dysfunction, it is reasonable to hypthesize that it may be reversed with folic acid. However, the methods of assessing endothelial function are relatively crude for the range of baseline homocysteine in this population. The results may have been influenced by the overwhelming effect of age on the brachial occlusion release methods. The ratio of nitrite/nitrate is a crude measure of endothelial NO and dependent on diet and smoking status as well.
1. Thambyrajah J, Landray MJ, Jones HJ, McGlynn FJ, Wheeler DC, Townsend JN. J Am Coll Cardiol 2001;37:1858–63.
Keywords: von Willebrand Factor, Homocysteine, Coronary Artery Disease, Brachial Artery, Nitrites, Folic Acid, Nitrates, Lipids, Blood Pressure, Diet, Smoking, Nitric Oxide
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