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 micromol/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 B6 and 6 microg of vitamin B12) 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 micromol/l; p < 0.001) whereas placebo had 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.