Towfighi Amytis, Arshi Baback, Markovic Daniela, Ovbiagele Bruce
Department of Neurology, University of Southern California, Los Angeles, Calif., USA.
Cerebrovasc Dis. 2014;37(4):263-7. doi: 10.1159/000360153. Epub 2014 Apr 15.
Clinical trials have failed to show a benefit of B vitamin therapy in reducing composite outcomes of cardiovascular death, myocardial infarction, and stroke among stroke survivors with elevated total serum homocysteine (tHcy) levels. Recent post hoc analyses have shown that numerous factors including age, baseline tHcy levels, folic acid fortification of grains, B12 status, renal function, comorbidities, and medications may modify the effect of B vitamin therapy on vascular risk in individuals with high tHcy. It remains possible that tHcy-lowering therapy may reduce cardiovascular risk in certain subgroups of stroke survivors. Post hoc subgroup analysis of the Heart Outcomes Prevention Evaluation-2 randomized controlled trial, which randomized participants with known cardiovascular disease to tHcy-lowering therapy or placebo, revealed larger treatment benefit for patients aged younger than 69 years; however, that analysis did not control for other factors. The aim of this study was to determine the effect of age on the impact of tHcy-lowering therapy for reducing vascular risk after stroke while controlling for other factors known to modify the effect of tHcy and tHcy-lowering therapy on vascular risk.
In this post hoc analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial, a randomized controlled trial of tHcy lowering for secondary stroke prevention, we excluded individuals who had poor renal function (glomerular filtration rate <47; the 10th percentile) or were treated with vitamin B12 injections. We assessed the effects of high-dose vitamin replacement on primary (stroke, myocardial infarction, or death) and secondary (stroke) outcomes, after stratifying by age (< vs. ≥ median age, 67 years) and adjusting for demographic and clinical factors.
This subgroup consisted of 2,993 individuals. Among individuals older than 67 years, high-dose vitamin therapy was associated with reduced risk of stroke, myocardial infarction or death (adjusted HR 0.76, 95% CI 0.58-0.99) and a trend towards reduced likelihood of stroke (adjusted HR 0.86, 95% CI 0.59-1.25). High-dose vitamin therapy did not impact outcomes among individuals younger than 67 years.
In this post hoc subgroup analysis of the VISP trial, age modified the association between B vitamin therapy and recurrent vascular risk among stroke survivors with elevated serum tHcy levels. Older individuals with stroke were more likely to benefit from B vitamin therapy than younger individuals. These findings can help inform the future design of clinical trials of tHcy-lowering therapy for cardiovascular risk reduction after stroke. © 2014 S. Karger AG, Basel.
临床试验未能证明，对于血清总同型半胱氨酸（tHcy）水平升高的中风幸存者，B族维生素疗法在降低心血管死亡、心肌梗死和中风的复合结局方面有获益。最近的事后分析表明，包括年龄、基线tHcy水平、谷物中的叶酸强化、维生素B12状态、肾功能、合并症和药物治疗等众多因素，可能会改变B族维生素疗法对高tHcy个体血管风险的影响。降低tHcy的疗法仍有可能在某些中风幸存者亚组中降低心血管风险。心脏结局预防评估-2随机对照试验的事后亚组分析将已知患有心血管疾病的参与者随机分为降低tHcy疗法组或安慰剂组，结果显示年龄小于69岁的患者治疗获益更大；然而，该分析未对其他因素进行控制。本研究的目的是在控制其他已知可改变tHcy及降低tHcy疗法对血管风险影响的因素的同时，确定年龄对降低tHcy疗法降低中风后血管风险的影响。
在这项对中风预防维生素干预（VISP）试验的事后分析中，该试验是一项降低tHcy以进行二级中风预防的随机对照试验，我们排除了肾功能差（肾小球滤过率<47；第10百分位数）或接受维生素B12注射治疗的个体。在按年龄（<与≥中位数年龄67岁）分层并对人口统计学和临床因素进行调整后，我们评估了高剂量维生素替代对主要结局（中风、心肌梗死或死亡）和次要结局（中风）的影响。
该亚组由2993名个体组成。在67岁以上的个体中，高剂量维生素疗法与中风、心肌梗死或死亡风险降低相关（调整后HR 0.76，95%CI 0.58 - 0.99），且有中风可能性降低的趋势（调整后HR 0.86，95%CI 0.59 - 1.25）。高剂量维生素疗法对67岁以下个体的结局没有影响。
在这项对VISP试验的事后亚组分析中，年龄改变了血清tHcy水平升高的中风幸存者中B族维生素疗法与复发性血管风险之间的关联。中风的老年个体比年轻个体更有可能从B族维生素疗法中获益。这些发现有助于为未来降低中风后心血管风险的降低tHcy疗法的临床试验设计提供参考。© 2014 S. Karger AG，巴塞尔。
