Chambers J C, Ueland P M, Obeid O A, Wrigley J, Refsum H, Kooner J S
National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Circulation. 2000 Nov 14;102(20):2479-83. doi: 10.1161/01.cir.102.20.2479.
Hyperhomocysteinemia is an independent risk factor for coronary heart disease (CHD). Dietary supplementation with B vitamins lowers plasma homocysteine by up to 30%. However, little is known about the potential beneficial effects of homocysteine lowering on vascular function in patients with CHD.
We investigated 89 men with CHD (aged 56 [range 39 to 67] years). Brachial artery flow-mediated dilatation (endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured before and 8 weeks after treatment with either (1) folic acid (5 mg) and vitamin B(12) (1 mg) daily (n=59) or (2) placebo (n=30). Total, protein-bound, and free plasma homocysteine, serum folate, and vitamin B(12) were measured at baseline and at 8 weeks. Flow-mediated dilatation improved after treatment with B vitamins (2.5+/-3.2% to 4.0+/-3.7%, P:=0.002) but not placebo (2.3+/-2.6% to 1.9+/-2.6%, P:=0.5). Vitamin therapy lowered plasma concentrations of total homocysteine (from 13.0+/-3.4 to 9.3+/-1.9 micromol/L, P:<0.001), protein-bound homocysteine (from 8.7+/-2.8 to 6.2+/-1.4 micromol/L, P:<0.001), and free homocysteine (from 4.3+/-1.2 to 3.0+/-0.6 micromol/L, P:<0.001) and raised concentrations of serum folate (from 10.3+/-4.3 to 31.2+/-10.8 ng/mL, P:<0.001) and vitamin B(12) (from 314+/-102 to 661+/-297 pg/mL, P:<0.001). In regression analysis, improved flow-mediated dilatation correlated closely with the reduction in free plasma homocysteine (r=-0.26, P:=0.001), independent of changes in protein-bound homocysteine, folate, and vitamin B(12). Nitroglycerin-induced dilatation was unchanged after both B vitamins and placebo.
Folic acid and vitamin B(12) supplementation improves vascular endothelial function in patients with CHD, and this effect is likely to be mediated through reduced concentrations of free plasma homocysteine concentrations. Our data support the view that lowering homocysteine, through B vitamin supplementation, may reduce cardiovascular risk.
高同型半胱氨酸血症是冠心病（CHD）的一个独立危险因素。饮食中补充B族维生素可使血浆同型半胱氨酸水平降低达30%。然而，关于降低同型半胱氨酸对冠心病患者血管功能的潜在有益作用，人们了解甚少。
我们对89例冠心病男性患者（年龄56岁[范围39至67岁]）进行了研究。在给予以下治疗前及治疗8周后，测量肱动脉血流介导的扩张（内皮依赖性）和硝酸甘油诱导的扩张（非内皮依赖性）：（1）每日服用叶酸（5毫克）和维生素B12（1毫克）（n = 59）或（2）安慰剂（n = 30）。在基线及8周时测量总血浆同型半胱氨酸、蛋白结合型同型半胱氨酸、游离血浆同型半胱氨酸、血清叶酸及维生素B12水平。服用B族维生素治疗后血流介导的扩张有所改善（从2.5±3.2%至4.0±3.7%，P = 0.002），而服用安慰剂则无改善（从2.3±2.6%至1.9±2.6%，P = 0.5）。维生素治疗降低了血浆总同型半胱氨酸浓度（从13.0±3.4降至9.3±1.9微摩尔/升，P < 0.001）、蛋白结合型同型半胱氨酸浓度（从8.7±2.8降至6.2±1.4微摩尔/升，P < 0.001）及游离同型半胱氨酸浓度（从4.3±1.2降至3.0±0.6微摩尔/升，P < 0.001），并提高了血清叶酸浓度（从10.3±4.3升至31.2±10.8纳克/毫升，P < 0.001）及维生素B12浓度（从314±102升至661±297皮克/毫升，P < 0.001）。在回归分析中，血流介导的扩张改善与游离血浆同型半胱氨酸的降低密切相关（r = -0.26，P = 0.001），与蛋白结合型同型半胱氨酸、叶酸及维生素B12的变化无关。服用B族维生素和安慰剂后，硝酸甘油诱导的扩张均无变化。
补充叶酸和维生素B12可改善冠心病患者的血管内皮功能，且这种作用可能是通过降低游离血浆同型半胱氨酸浓度介导的。我们的数据支持以下观点，即通过补充B族维生素降低同型半胱氨酸水平可能降低心血管疾病风险。
