Effect of homocysteine-lowering therapy on vascular endothelial function and exercise performance in coronary patients with hyperhomocysteinaemia

Objective -This study was performed to determine the effect of homocysteine-lowering therapy (HLT) on endothelium-dependent vasodilation (EDD) and exercise performance in patients with coronary artery disease. Methods and Results - Among the patients who were on the waiting list for coronary intervention, 26 male patients (plasma homocysteine (Hcy) levels > 15 mumol/l) who had a focal stenosis of at least 70% in the left anterior descending artery were included in the study.The patients were matched to receive HLT (n = 15; 0.4 mg of folic acid, 2 mg vitamin B-6 and 6 mug of vitamin B-12) or placebo (n = 11) until the coronary intervention was performed (mean 3.8 +/- 0.9 weeks). Brachial artery vasomotion test and treadmill stress testing were performed at baseline and 4 weeks after HLT before the time of coronary intervention in each patient. Hcy levels were found to be decreased significantly after HLT compared to baseline (23.4 +/- 6 vs. 11.3 +/- 4 mumol/l; p<0.001) whereas placebo ad no effect. HLT but not placebo produced a marked improvement in EDD, from 3.9 +/- 1.1% to 9.4 +/- 2.3% (p<0.0001). Endothelium-independent nitroglycerin-induced dilation was similar in the HLT and placebo groups compared with the baseline. In the exercise testing, HLT resulted in a significant improvement in exercise duration and reduction in the amount of maximal ST-segment depression, (from 6.5 +/- 2 to 6.9 +/- 2 min, p = 0.02 and from 1.2 +/- 0.7 to 0.8 +/- 0.5 mm, p = 0.01, respectively) whereas placebo did not. Conclusion - Lowering Hcy levels improves EDD and exercise performance while reducing the exercise-induced myocardial ischaemia in patients with coronary heart disease and hyperhomocysteinaemia.