The Effect of Homocysteine-Lowering Therapy on Vascular Endothelial Function and Myocardial Ischemic Burden in Coronary Patients with Hyperhomocysteinemia [Turk Kardiyol Dern Ars]
Turk Kardiyol Dern Ars. 2000; 28(10): 598-606

The Effect of Homocysteine-Lowering Therapy on Vascular Endothelial Function and Myocardial Ischemic Burden in Coronary Patients with Hyperhomocysteinemia

Mehmet AKSOY1, İlyas AKDEMİR1, Ş.Nur AKSOY2, Mete ÖÇ3, Metin GÜRSÜRER3, Ayşe EMRE3, M.Vefik YAZICIOĞLU3, Müjgan B. MİHMANLI3, Macit KOLDAŞ2, Birsen ERSEK3
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This study was performed to determine whether homocysteine-lowering therapy (HLT) improves endothelium-dependent vasodilation and whether this results in a reduction in myocardial ischemic burden in patients with coronary artery disease. Sixteen male patients (plasma homocysteine levels > 15 µmol/L) on a waiting list for routine coronary angioplasty (PTCA) of a focal stenosis at least 70% in the left anterior descending artery were studied. Patients were randomized to receive HLT (n=9, 0.4 mg of folic acid, 2 mg of vitamin B6, and 6 µg of vitamin B12) or placebo (n=7) until the time of PTCA (mean 4.8±0.9 weeks). At baseline and after four weeks of HLT, brachial artery vasomotion was assessed noninvasively and exercise Tl-201 scintigraphy was performed in each patient. Myocardial ischemic burden was defined as maximal perfusion defect and redistribution gradient of perfusion abnormality on the polar map display. All patients had a follow-up angiogram at the time of PTCA. Plasma homocysteine levels were significantly reduced by HLT compared with baseline (21.2±5 vs. 11.8±3. 1 µmol/L; p<0.008) whereas placebo had no effect (19.9±5 vs. 20.2±7 µmol/L; p=NS). HLT produced a marked improvement in endothelium dependent, flowmediated dilation, from 3.8±1.3% to 9.2±2.2 (p<0.0001). There was no significant change in flow-mediated dilation with placebo (3.7±1.3% vs. 3.8± 1.6%; p=NS). Endothelium-independent, nitroglycerin-induced dilation was similar in the HLT (12.3±2.4% vs. 13.1±1.9%; p=NS) and placebo (13.2±2.2% vs. 12.9±2.8%; p=NS) groups compared with baseline. HLT resulted in significant reductions in maximal perfusion defect, from 52±21% to 42±17% (p=0.004) and in redistribution gradient, from 24.8± 13% to 16. 7±8% (p=0.006) whereas placebo did not. The severity of stenosis was not different between the initial and follow-up angiograms in HLT (81±9% vs. 82± 11 %; p=NS) and placebo (79±8% vs. 80±9%; p=NS) groups. In addition, the degree of reduction in plasma homocysteine level was negatively correlated with endothelium dependent vasodilation (r=-0.63, p=0.05). Improvement in endothelium dependent vasodilation was also negatively correlated with maximal perfusion defect (r=-0.65, p=0.05) and redistribution gradient (r=-0.67, p=0.04). In conclusion, lowering plasma homocysteine levels with HLT improves endothelium-dependent vasodilation and this may result in a reduction in exercise-induced myocardial ischemia in coronary patients with hyperhomocysteinemia.

Keywords: Homocysteine, endothelial function, myocardial ischemia, exercise Tl-201 scintigraphy

How to cite this article
Mehmet AKSOY, İlyas AKDEMİR, Ş.Nur AKSOY, Mete ÖÇ, Metin GÜRSÜRER, Ayşe EMRE, M.Vefik YAZICIOĞLU, Müjgan B. MİHMANLI, Macit KOLDAŞ, Birsen ERSEK. The Effect of Homocysteine-Lowering Therapy on Vascular Endothelial Function and Myocardial Ischemic Burden in Coronary Patients with Hyperhomocysteinemia. Turk Kardiyol Dern Ars. 2000; 28(10): 598-606
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