Chia Stanley, Wilson Robert, Ludlam Christopher A, Webb David J, Flapan Andrew D, Newby David E
Department of Cardiology, National Heart Centre, 17 Hospital Avenue, Singapore 168752, Republic of Singapore.
Clin Sci (Lond). 2005 Jan;108(1):65-72. doi: 10.1042/CS20040150.
Hyperhomocysteinaemia is a prothrombotic condition that may cause oxidative endothelial injury and impair endogenous fibrinolysis. Vitamin supplementation enhances endothelial function in hyperhomocysteinaemic patients, but responses in patients with co-existing coronary artery disease have been variable. It is also unknown whether hyperhomocysteinaemia is associated with reduced fibrinolytic responses in patients with coronary artery disease. The study aims were to test the hypothesis that patients with recent myocardial infarction and hyperhomocysteinaemia have impaired endothelium-dependent vasomotion and fibrinolysis that is rectified by vitamin supplementation. From a cohort of 120 patients admitted with acute myocardial infarction, 18 patients were recruited from the upper (n=9) and lower (n=9) plasma homocysteine quartiles into a randomized double-blind placebo-controlled crossover trial. Following a 4-week course of placebo or folate/cyanocobalamin/pyridoxine supplements, FBF (forearm blood flow) was measured using venous occlusion plethysmography during intra-arterial substance P (4-16 pmol/min), acetylcholine (5-20 microg/min) and sodium nitroprusside (2-8 microg/min) infusions. All vasodilators caused dose-dependent increases in infused FBF (P<0.05). Patients in the upper homocysteine quartile (16.8+/-2.9 compared with 7.9+/-0.7 micromol/l; P=0.003) had reduced vasodilatation to acetylcholine (P=0.01) and substance P (P<0.05), but not sodium nitroprusside. There were no differences in substance P-induced tissue plasminogen activator release. Vitamin supplementation increased serum folate and vitamin B12 concentrations (P<0.05), but did not significantly lower homocysteine, or affect FBF or fibrinolytic responses. In patients with recent myocardial infarction, hyperhomocysteinaemia is associated with impaired endothelium-dependent vasodilatation, but no alteration in the acute fibrinolytic capacity. This endothelial vasomotor dysfunction is unaltered by vitamin supplementation.
高同型半胱氨酸血症是一种促血栓形成状态，可能导致内皮氧化损伤并损害内源性纤维蛋白溶解。补充维生素可增强高同型半胱氨酸血症患者的内皮功能，但合并冠状动脉疾病患者的反应存在差异。高同型半胱氨酸血症是否与冠状动脉疾病患者纤维蛋白溶解反应降低相关也尚不清楚。本研究的目的是检验以下假设：近期发生心肌梗死且患有高同型半胱氨酸血症的患者存在内皮依赖性血管运动和纤维蛋白溶解受损，补充维生素可纠正这一情况。在120例因急性心肌梗死入院的患者队列中，从血浆同型半胱氨酸四分位数的上（n = 9）、下（n = 9）四分位数中招募了18例患者，进行一项随机双盲安慰剂对照交叉试验。在服用4周安慰剂或叶酸/氰钴胺素/吡哆醇补充剂后，在动脉内注入P物质（4 - 16 pmol/min）、乙酰胆碱（5 - 20 μg/min）和硝普钠（2 - 8 μg/min）期间，使用静脉阻塞体积描记法测量前臂血流量（FBF）。所有血管扩张剂均导致注入的FBF呈剂量依赖性增加（P < 0.05）。同型半胱氨酸四分位数较高的患者（16.8±2.9与7.9±0.7 μmol/L相比；P = 0.003）对乙酰胆碱（P = 0.01）和P物质（P < 0.05）的血管扩张反应降低，但对硝普钠无此反应。P物质诱导的组织纤溶酶原激活物释放无差异。补充维生素可提高血清叶酸和维生素B12浓度（P < 0.05），但未显著降低同型半胱氨酸水平，也未影响FBF或纤维蛋白溶解反应。在近期发生心肌梗死的患者中，高同型半胱氨酸血症与内皮依赖性血管舒张受损相关，但急性纤维蛋白溶解能力无改变。补充维生素并未改变这种内皮血管运动功能障碍。
