Bleie Ø, Semb A G, Grundt H, Nordrehaug J E, Vollset S E, Ueland P M, Nilsen D W T, Bakken A M, Refsum H, Nygård O K
Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
J Intern Med. 2007 Aug;262(2):244-53. doi: 10.1111/j.1365-2796.2007.01810.x.
A high level of total homocysteine (tHcy) is a risk marker for cardiovascular disease (CVD), and is related to inflammation. We wanted to test the effect of homocysteine-lowering B-vitamin therapy, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on inflammatory markers associated with atherosclerosis.
Single centre, prospective double-blind clinical interventional study, randomised in a 2 x 2 factorial design.
Ninety patients (21 female) with suspected coronary artery disease (CAD), aged 38-80 years, were blindly randomised into one of four groups of daily oral treatment with (A) folic acid (0.8 mg)/vitamin B12 (0.4 mg)/vitamin B6 (40 mg), (B) folic acid/vitamin B12, (C) vitamin B6 alone or (D) placebo. Blood samples were collected before and after 6 months of treatment.
Before intervention, median levels of the analytes were: tHcy 11.0 micromol L(-1), neopterin 8.1 nmol L(-1), soluble CD40 ligand (sCD40L) 3.9 ng mL(-1), interleukin (IL)-6 1.9 pg mL(-1), C-reactive protein (CRP) 1.9 mg L(-1) and low-density lipoprotein (LDL) cholesterol 3.3 mmol L(-1). tHcy was significantly associated with neopterin (r = 0.49, P < 0.001) and with IL-6 (r = 0.29, P = 0.01), but not with CRP or sCD40L. Neither treatment with folic acid/B12 nor with B6 induced significant changes in any of these inflammatory biomarkers (P >or= 0.14). In patients receiving folic acid/B12 (groups A and B), tHcy was reduced with 33% (P < 0.001).
In patients with stable CAD, homocysteine-lowering therapy with B-vitamins does not affect levels of inflammatory markers associated with atherogenesis. Failure to reverse inflammatory processes, may partly explain the negative results in clinical secondary B-vitamin intervention trials.
高总同型半胱氨酸（tHcy）水平是心血管疾病（CVD）的风险标志物，且与炎症相关。我们旨在测试挪威西部B族维生素干预试验（WENBIT）中使用的降低同型半胱氨酸的B族维生素疗法对与动脉粥样硬化相关的炎症标志物的影响。
单中心、前瞻性双盲临床干预研究，采用2×2析因设计进行随机分组。
90例疑似冠心病（CAD）患者（21例女性），年龄38 - 80岁，被随机分为四组，分别每日口服（A）叶酸（0.8毫克）/维生素B12（0.4毫克）/维生素B6（40毫克）、（B）叶酸/维生素B12、（C）单独维生素B6或（D）安慰剂。在治疗6个月前后采集血样。
干预前，分析物的中位数水平为：tHcy 11.0微摩尔/升，新蝶呤8.1纳摩尔/升，可溶性CD40配体（sCD40L）3.9纳克/毫升，白细胞介素（IL）-6 1.9皮克/毫升，C反应蛋白（CRP）1.9毫克/升，低密度脂蛋白（LDL）胆固醇3.3毫摩尔/升。tHcy与新蝶呤显著相关（r = 0.49，P < 0.001），与IL-6相关（r = 0.29，P = 0.01），但与CRP或sCD40L无关。叶酸/B12治疗和B6治疗均未引起这些炎症生物标志物中的任何一项发生显著变化（P≥0.14）。在接受叶酸/B12治疗的患者（A组和B组）中，tHcy降低了33%（P < 0.001）。
在稳定型CAD患者中，用B族维生素降低同型半胱氨酸的疗法不会影响与动脉粥样硬化发生相关的炎症标志物水平。未能逆转炎症过程，可能部分解释了B族维生素临床二级干预试验的阴性结果。
