Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials
Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials
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DOI：
10.1111/j.1365-2796.2010.02259.x
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发表时间：
2010-10-01
影响因子：
11.1
通讯作者：
Nygard, O.
中科院分区：
文献类型：
--
作者：
Ebbing, M.;Bonaa, K. H.;Nygard, O.
埃宾M.，B圈划分为K.H.，阿内森·E尤兰德·P·M Nordrehaug J.E.，Rasmussen K.，NJ Circle Divide Istad I.，尼尔森·D·W雷夫苏姆·H.，特维尔达尔A.，Vollset S.E.，Schirmer H.，Bleie Circle Divide. Steigen T.，中间圈分界线，弗雷德里克森A.，佩德森急诊室，尼加德岛(From 1Heart Disease，Haukeland University Hospital，卑尔根; Heart Disease，University Hospital of North Norway; Department of Community Medicine，University of特罗姆circle divide，特罗姆circle divide; Institute of Medicine，University of卑尔根，卑尔根; Department of Clinical Medicine，University of Troms circle divide，Troms circle divide; Department of Cardiology，Stavanger University Hospital，斯塔万格;基础医学科学研究所，奥斯陆大学，奥斯陆，挪威;生理学、解剖学和遗传学系，牛津大学，牛津，英国;流行病学系，挪威公共卫生研究所，奥斯陆;公共卫生和初级卫生保健系，卑尔根大学; Bevital AS，卑尔根;两项降低同型半胱氨酸的B族维生素随机对照试验的联合分析和扩展随访。在挪威维生素试验和挪威西部B族维生素干预试验中，患者被随机分配接受降低同型半胱氨酸的B族维生素治疗或不接受此类治疗。我们在试验期间和延长随访期间，研究了它们对试验人群合并的心血管结局的影响，并进行探索性分析，以确定高半胱氨酸作为心血管结局预测因子的有效性。设计。两项随机对照试验的数据汇总（1998-2005），延长试验后观察随访至2008年1月1日。研究对象：6837名缺血性心脏病患者。干预措施：每天一粒含叶酸的胶囊（0.8毫克）加维生素B12（0.4 mg）和维生素B6（40 mg），或叶酸加维生素B12，或维生素B6单独或安慰剂。主要结果指标。（行政实体;心血管死亡，急性心肌梗死或卒中）和延长随访期间的心血管死亡率-结果：叶酸加维生素B12治疗使同型半胱氨酸水平降低25%，但不影响MACE发生率（风险比，1.07; 95% CI，0.95-1.21），或心血管死亡率（风险比，1.12; 95% CI，0.95-1.31）。基线同型半胱氨酸水平与研究结果无关。然而，1-2个月的叶酸加维生素B12治疗后测得的同型半胱氨酸浓度是一个强有力的预测MACEs.Conclusion。我们发现没有短期或长期的好处，叶酸加维生素B12对缺血性心脏病患者的心血管结局。我们的数据表明，通过血浆总同型半胱氨酸浓度预测心血管风险可能仅限于对B族维生素无反应的同型半胱氨酸部分。
Ebbing M., B circle divide naa K.H., Arnesen E., Ueland P.M., Nordrehaug J.E., Rasmussen K., Nj circle divide lstad I., Nilsen D.W., Refsum H., Tverdal A., Vollset S.E., Schirmer H., Bleie circle divide., Steigen T., Midttun circle divide., Fredriksen A., Pedersen E.R., Nygard O. (From the Departments of 1Heart Disease, Haukeland University Hospital, Bergen; Heart Disease, University Hospital of North Norway; Department of Community Medicine, University of Troms circle divide, Troms circle divide; Institute of Medicine, University of Bergen, Bergen; Department of Clinical Medicine, University of Troms circle divide, Troms circle divide; Department of Cardiology, Stavanger University Hospital, Stavanger; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK; Division of Epidemiology, the Norwegian Institute of Public Health, Oslo; Department of Public Health and Primary Health Care, University of Bergen; Bevital AS, Bergen; Norway) Combined Analyses and Extended Follow-Up of Two Randomized Controlled Homocysteine-Lowering B-Vitamin Trials. J Intern Med 2010; 268: 367-382.Objectives.In the Norwegian Vitamin Trial and the Western Norway B Vitamin Intervention Trial, patients were randomly assigned to homocysteine-lowering B-vitamins or no such treatment. We investigated their effects on cardiovascular outcomes in the trial populations combined, during the trials and during an extended follow-up, and performed exploratory analyses to determine the usefulness of homocysteine as a predictor of cardiovascular outcomes.Design.Pooling of data from two randomized controlled trials (1998-2005) with extended post-trial observational follow-up until 1 January 2008.Setting.Thirty-six hospitals in Norway.Subjects.6837 patients with ischaemic heart disease.Interventions.One capsule per day containing folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg), or folic acid plus vitamin B12, or vitamin B6 alone or placebo.Main outcome measures.Major adverse cardiovascular events (MACEs; cardiovascular death, acute myocardial infarction or stroke) during the trials and cardiovascular mortality during the extended follow-up.Results.Folic acid plus vitamin B12 treatment lowered homocysteine levels by 25% but did not influence MACE incidence (hazard ratio, 1.07; 95% CI, 0.95-1.21) during 39 months of follow-up, or cardiovascular mortality (hazard ratio, 1.12; 95% CI, 0.95-1.31) during 78 months of follow-up, when compared to no such treatment. Baseline homocysteine level was not independently associated with study outcomes. However, homocysteine concentration measured after 1-2 months of folic acid plus vitamin B12 treatment was a strong predictor of MACEs.Conclusion.We found no short- or long-term benefit of folic acid plus vitamin B12 on cardiovascular outcomes in patients with ischaemic heart disease. Our data suggest that cardiovascular risk prediction by plasma total homocysteine concentration may be confined to the homocysteine fraction that does not respond to B-vitamins.