Van den Berg M, Boers G H, Franken D G, Blom H J, Van Kamp G J, Jakobs C, Rauwerda J A, Kluft C, Stehouwert C D
Department of Vascular Surgery, Free University Hospital, Amsterdam, The Netherlands.
Eur J Clin Invest. 1995 Mar;25(3):176-81. doi: 10.1111/j.1365-2362.1995.tb01545.x.
Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL-1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.
高同型半胱氨酸血症的定义为口服蛋氨酸负荷后血浆同型半胱氨酸浓度异常升高，这在年轻（≤50岁）的外周动脉闭塞性疾病患者中很常见。人们认为它会通过损伤血管内皮而导致动脉粥样硬化。用吡哆醇和/或叶酸治疗可能会降低血浆同型半胱氨酸水平。在患有外周动脉闭塞性疾病的轻度高同型半胱氨酸血症患者中，我们研究了每日服用吡哆醇（250毫克）加叶酸（5毫克）对同型半胱氨酸代谢（即48例患者禁食状态下及蛋氨酸负荷后的血浆浓度）和内皮功能（18例患者）的影响。内皮功能通过内皮衍生蛋白血管性血友病因子（vWF）、血栓调节蛋白（TM）和组织型纤溶酶原激活剂（tPA）的血浆浓度来评估。基线时，48例患者中有24例（50%）的空腹同型半胱氨酸水平高于正常；根据定义，负荷后水平在所有患者中均高于正常。治疗12周后，98%和100%的患者空腹及负荷后水平分别恢复正常。对完成1年治疗的18例患者进行了内皮功能评估。基线时，vWF中位数（235%）和TM水平（57.1纳克/毫升）高于正常。随访时，vWF水平降至170%（P = 0.01），TM水平降至49纳克/毫升（P = 0.04）。tPA水平在基线时正常且未发生变化。外周动脉闭塞性疾病和高同型半胱氨酸血症的年轻患者存在内皮功能障碍。吡哆醇加叶酸治疗几乎能使所有患者的同型半胱氨酸代谢恢复正常，且似乎能改善内皮功能障碍。
