Vermeulen E G J, Stehouwer C D A, Valk J, van der Knaap M, van den Berg M, Twisk J W R, Prevoo W, Rauwerda J A
'Vrije Universiteit' Medical Center (VUMC), Institute for Cardiovascular Research (IcaR-VU), Amserdam, the Netherlands.
Eur J Clin Invest. 2004 Apr;34(4):256-61. doi: 10.1111/j.1365-2362.2004.01332.x.
A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine-lowering treatment with folic acid plus vitamin B(6) on markers of cerebrovascular atherosclerosis and cerebral microangiopathy.
Using 158 healthy siblings (mean age 46.0 +/- 7.6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo-controlled trial using 5 mg of folic acid plus 250 mg of vitamin B(6) daily (n = 78) or placebo medication (n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy).
Seventeen (10.8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61.8%) and 48 (65.8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty-four participants (15.2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13-fold vs. placebo; P < 0.001) and vitamin B(6) (8.8-fold; P < 0.001). Fasting and postmethionine total homocysteine concentrations decreased 38.7% (95% CI, 27.4-50.0) and 29.1% (95% CI, 19.2-39.0) vs. placebo (all P < 0.001). During follow up six individuals in the vitamin-treated and 11 in the placebo-treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0.48; 95% CI 0.17-1.41; P = 0.18 and 0.48; CI 0.14-1.60; P = 0.23, respectively).
These results could indicate a possible favourable effect of homocysteine-lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.
高血浆同型半胱氨酸浓度是大血管及可能的小血管疾病的独立危险因素。我们研究了叶酸加维生素B6降低同型半胱氨酸治疗对脑血管动脉粥样硬化和脑微血管病变标志物的影响。
我们选取了158名患有早发性动脉粥样硬化疾病患者的健康同胞（平均年龄46.0±7.6岁），进行了一项随机、安慰剂对照试验，其中78人每日服用5毫克叶酸加250毫克维生素B6（n = 78），80人服用安慰剂（n = 80）。通过磁共振血管造影（MRA）（颈动脉狭窄；颈动脉和/或椎动脉延长）和磁共振成像（MRI）（白质异常；脑萎缩）对参与者进行了2年的随访。
17名（10.8%）受试者因幽闭恐惧症拒绝接受MRA/MRI检查而被排除。在其余141名参与者中，68人接受了维生素治疗，73人接受了安慰剂治疗[分别有42人（61.8%）和48人（65.8%）存在蛋氨酸负荷后高同型半胱氨酸血症]。24名参与者（15.2%；治疗组10人，安慰剂组14人）未完成两年的试验。维生素治疗使血浆叶酸增加了13倍（与安慰剂相比；P < 0.001），维生素B6增加了8.8倍（P < 0.001）。空腹和蛋氨酸负荷后总同型半胱氨酸浓度与安慰剂相比分别降低了38.7%（95%CI，27.4 - 50.0）和29.1%（95%CI，19.2 - 39.0）（所有P < 0.001）。在随访期间，维生素治疗组有6人，安慰剂治疗组有11人在结局测量方面病情恶化。与安慰剂相比，维生素治疗在MRA和MRI结局测量方面均有非显著改善（优势比0.48；95%CI 0.17 - 1.41；P = 0.18和0.48；CI 0.14 - 1.60；P = 0.23）。
这些结果可能表明，在患有早发性动脉粥样硬化疾病患者的健康同胞中，降低同型半胱氨酸治疗对脑血管动脉粥样硬化和脑微血管病变可能有有利影响，但需要更大规模的试验来确定这一点。
