Vermeulen E G, Stehouwer C D, Twisk J W, van den Berg M, de Jong S C, Mackaay A J, van Campen C M, Visser F C, Jakobs C A, Bulterjis E J, Rauwerda J A
Department of General Surgery, University Hospital and Institute for Cardiovascular Research Vrije Universiteit, Amsterdam, The Netherlands.
Lancet. 2000 Feb 12;355(9203):517-22. doi: 10.1016/s0140-6736(99)07391-2.
A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease.
We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography.
Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14.7 to 7.4 micromol/L vs from 14.7 to 12.0 micromol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 micromol/L vs from 64.8 to 50.3 micromol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0.87 [0.56-1.33]), or on carotid and peripheral-arterial outcome variables (1.02 [0.26-4.05] and 0.86 [0.47-1.59], respectively).
Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.
血浆同型半胱氨酸浓度升高与动脉粥样硬化血栓形成性疾病风险增加相关。我们研究了降低同型半胱氨酸治疗（叶酸加维生素B6）对早发性动脉粥样硬化血栓形成性疾病患者健康同胞中亚临床动脉粥样硬化标志物的影响。
我们对167例早发性动脉粥样硬化血栓形成性疾病患者的158名健康同胞进行了一项随机、安慰剂对照试验。80人被分配接受安慰剂，78人被分配每天服用5毫克叶酸和250毫克维生素B6，为期2年。主要终点是根据运动心电图、踝臂压力指数以及颈动脉和股动脉超声检查评估的亚临床动脉粥样硬化的发生或进展。
治疗组有10名参与者退出，安慰剂组有14名参与者退出。与安慰剂相比，维生素治疗可使空腹同型半胱氨酸浓度降低（从14.7微摩尔/升降至7.4微摩尔/升，而安慰剂组从14.7微摩尔/升降至12.0微摩尔/升），蛋氨酸负荷后同型半胱氨酸浓度也降低（从64.9微摩尔/升降至34.9微摩尔/升，而安慰剂组从64.8微摩尔/升降至50.3微摩尔/升）。它还与运动心电图异常检查率降低相关（比值比0.40 [0.17 - 0.93]；p = 0.035）。维生素治疗对踝臂压力指数（0.87 [0.56 - 1.33]）或颈动脉和外周动脉结局变量（分别为1.02 [0.26 - 4.05]和0.86 [0.47 - 1.59]）没有明显影响。
在早发性动脉粥样硬化血栓形成性疾病患者的健康同胞中，用叶酸加维生素B6进行降低同型半胱氨酸治疗与运动心电图异常检查发生率降低相关，这与动脉粥样硬化性冠状动脉事件风险降低一致。
