Schernthaner G-H, Plank C, Minar E, Bieglmayer C, Koppensteiner R, Schernthaner G
Department of Internal Medicine II, Medical University of Vienna, and Department of Internal Medicine I, Rudolfstiftung Hospital, Vienna, Austria.
Eur J Clin Invest. 2006 May;36(5):333-9. doi: 10.1111/j.1365-2362.2006.01639.x.
Although peripheral arterial occlusive disease (PAOD) is significantly associated with elevated homocysteine levels, the clinical relevance of hyperhomocysteinaemia for the prevention and progression of PAOD is still unknown.
A total of 65 patients suffering from symptomatic PAOD with elevated homocysteine levels were randomized onto placebo or B-vitamins (50 mg thiaminhydrochlorid, 50 mg pyridoxine, and 0.05 mg cyanocobalamin), plus 5 mg folic acid daily for 6 weeks. Serum levels of folic acid, vitamin B12, creatinine, ultra-sensitive C-reactive protein (usCRP), interleukin (IL)-6, IL-8, IL-18, monocyte-chemo-attractant-protein-1 (MCP-1) and plasma levels of homocysteine, tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were determined on the 1st day and 42nd day. Primary outcome was reduction of homocysteine, secondary outcomes were reduction of usCRP, IL-6, IL-8, Il-18, MCP-1, TF and TFPI.
The mean reduction of homocysteine concentration was 33% (95%CI 33.36-55.76, or 18.9+/-5.4 micromol L-1-12.6+/-2.8 micromol L-1, P=0) in the B-vitamin group compared with 1% in the placebo group. Folic acid (P=0) and vitamin B12 (P=0) increased significantly in the verum group, but both remained unchanged in the control group. No treatment effect of lowering of homocysteine on any markers of haemostasis (TF, TFPI) or inflammation (usCRP, IL-6, IL-8, IL-18 and MCP-1) was observed.
Although homocysteine is associated with vascular disease risk in the general population and in particular with PAOD, marked lowering of homocysteine concentrations by folic acid and B-vitamin supplementation does not influence inflammatory responses involving usCRP, IL-6, IL-8, IL-18 and MCP-1, nor tissue factor. These results provide evidence against a major effect of hyperhomocysteinaemia on vascular chronic inflammation or coagulation in patients with symptomatic peripheral arterial occlusive disease.
尽管外周动脉闭塞性疾病（PAOD）与同型半胱氨酸水平升高显著相关，但高同型半胱氨酸血症对PAOD预防和进展的临床相关性仍不明确。
总共65例有症状的PAOD且同型半胱氨酸水平升高的患者被随机分为接受安慰剂组或B族维生素组（50mg盐酸硫胺、50mg吡哆醇和0.05mg氰钴胺），外加每日5mg叶酸，持续6周。在第1天和第42天测定血清叶酸、维生素B12、肌酐、超敏C反应蛋白（usCRP）、白细胞介素（IL）-6、IL-8、IL-18、单核细胞趋化蛋白-1（MCP-1）以及血浆同型半胱氨酸、组织因子（TF）和组织因子途径抑制剂（TFPI）水平。主要结局是同型半胱氨酸的降低，次要结局是usCRP、IL-6、IL-8、Il-18、MCP-1、TF和TFPI的降低。
与安慰剂组1%的降低相比，B族维生素组同型半胱氨酸浓度平均降低33%（95%CI 33.36 - 55.76，或从18.9±5.4μmol/L降至12.6±2.8μmol/L，P = 0）。真药组叶酸（P = 0）和维生素B12（P = 0）显著增加，而对照组两者均无变化。未观察到降低同型半胱氨酸对任何止血标志物（TF、TFPI）或炎症标志物（usCRP、IL-6、IL-8、IL-18和MCP-1）有治疗效果。
尽管在普通人群中，尤其是PAOD患者中，同型半胱氨酸与血管疾病风险相关，但通过补充叶酸和B族维生素显著降低同型半胱氨酸浓度，并不会影响涉及usCRP、IL-6、IL-8、IL-18和MCP-1的炎症反应，也不会影响组织因子。这些结果为反对高同型半胱氨酸血症对有症状外周动脉闭塞性疾病患者的血管慢性炎症或凝血有主要影响提供了证据。
