Homocysteine lowering for stroke prevention: Unravelling the complexity of the evidence
Homocysteine lowering for stroke prevention: Unravelling the complexity of the evidence
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DOI：
10.1177/1747493016662038
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发表时间：
2016-10-01
影响因子：
6.7
通讯作者：
Spence, J. David
中科院分区：
文献类型：
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作者：
Spence, J. David
总同型半胱氨酸水平升高损害内皮功能障碍并增加血栓形成。同型半胱氨酸在动物模型中是因果关系，在人体研究中，总同型半胱氨酸升高与颈动脉粥样硬化、腔隙性梗死和房颤中卒中风险显著增加显著相关。因为两个早期的B族维生素治疗的大型试验（维生素干预预防中风和挪威维生素研究）没有显示中风减少，心脏结局预防评估2试验被错误地解释为没有显示中风减少（因为作者无法想到中风和心肌梗死之间的生物学差异），对于通过降低总高半胱氨酸来预防中风的治疗存在广泛的悲观情绪。然而，心脏结局预防评估2试验，叶酸和欧米茄三油的法国试验，不包括抗血小板治疗的预防中风的维生素亚组都显示中风显著减少。维生素干预预防中风试验结果为阴性的原因包括北美的叶酸强化，为基线血清B12低的患者提供B12注射，以及事实证明，氰钴胺中的氰化物对肾功能受损的参与者造成了伤害。在糖尿病肾病维生素干预试验中，包括氰钴胺在内的B族维生素是有害的，在排除接受B12注射和肾功能受损的参与者的维生素干预预防卒中亚组中，卒中/心肌梗死/血管性死亡的发生率在统计学上显著降低。2015年，中国脑卒中一级预防试验（CSPPT）对超过20，000名参与者进行了5年的随访，结果显示，在未实施叶酸强化的情况下，叶酸可显著降低卒中发生率。在叶酸强化的情况下，总同型半胱氨酸升高的主要原因是肾功能衰竭和代谢性B12缺乏;后者在中风患者中非常常见（71岁以上30%），并且经常被遗漏。对脑卒中患者应常规检测血清B12和总同型半胱氨酸，并对升高的总同型半胱氨酸进行治疗。
Elevated levels of total homocysteine impair endothelial dysfunction and increase thrombosis. Homocysteine is causal in animal models, and in human studies, elevated total homocysteine is significantly associated with carotid atherosclerosis, lacunar infarction, and markedly increased risk of stroke in atrial fibrillation. Because two of the early large trials of B vitamin therapy (Vitamin Intervention for Stroke Prevention and the Norwegian Vitamin Study) did not show any reduction of stroke, and the Heart Outcomes Prevention Evaluation 2 trial was mistakenly interpreted as not showing a reduction of stroke (because the authors could not think of a biological difference between stroke and myocardial infarction), there has been widespread pessimism regarding treatment to lower total homocysteine for stroke prevention. However, the Heart Outcomes Prevention Evaluation 2 trial, the French trial of folic acid and omega three oils, the Vitamins to Prevent Stroke subgroup excluding antiplatelet therapy all showed a significant reduction of stroke. Reasons why the Vitamin Intervention for Stroke Prevention trial were negative included folate fortification in North America, provision of injections of B12 to patients with low baseline serum B12, and as it turns out, harm from cyanide in cyanocobalamin among participants with impaired renal function. In the Diabetic Intervention with Vitamins in Nephropathy trial, B vitamins including cyanocobalamin were harmful, and in a Vitamin Intervention for Stroke Prevention subgroup excluding participants who received B12 injections and those with impaired renal function, there was a statistically significant reduction of stroke/myocardial infarction/vascular death. In 2015, the China Stroke Primary Prevention Trial (CSPPT), in over 20,000 participants followed for 5 years, showed a significant reduction of stroke with folic acid in a setting where folate fortification has not been implemented. In the setting of folate fortification, the main causes of elevated total homocysteine are renal failure and metabolic B12 deficiency; the latter is very common among stroke patients (30% over age 71), and frequently missed. Serum B12 and total homocysteine should be checked routinely in stroke patients and elevated total homocysteine should be treated.