Plasma homocysteine as a risk factor for vascular disease - The European concerted action project
Plasma homocysteine as a risk factor for vascular disease - The European concerted action project
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DOI：
10.1001/jama.277.22.1775
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发表时间：
1997-06-11
影响因子：
120.7
通讯作者：
Andria, G
中科院分区：
文献类型：
--
作者：
Graham, IM;Daly, LE;Andria, G
背景。-血浆同型半胱氨酸升高是动脉粥样硬化血管疾病的已知危险因素，但这种关系的强度以及血浆同型半胱氨酸与其他危险因素的相互作用尚不清楚。建立与血浆同型半胱氨酸水平升高相关的血管疾病风险的大小，并检查血浆同型半胱氨酸水平升高与传统风险因素之间的相互作用。病例对照研究。设置。- 9个欧洲国家的19个中心。共有750例动脉粥样硬化性血管疾病（心脏，大脑和外周）和800名年龄小于60岁的男性和女性对照。血浆总同型半胱氨酸测定受试者空腹和标准化蛋氨酸负荷试验后，这涉及到每公斤100毫克蛋氨酸的管理，并强调负责同型半胱氨酸的不可逆降解的代谢途径。血浆钴胺素，吡哆醛5 '-磷酸，红细胞叶酸，血清胆固醇，吸烟，血压也进行了测量。对照组空腹总同型半胱氨酸分布的前五分之一与后五分之四相比，血管疾病的相对风险为2.2（95%置信区间，1.6-2.9）。甲硫氨酸负荷确定了额外的27%的高危病例。总同型半胱氨酸水平和风险之间存在剂量反应效应。风险是类似的，独立于其他危险因素，但同型半胱氨酸和这些危险因素之间的相互作用的影响，对于两种性别相结合，空腹同型半胱氨酸水平的增加显示了吸烟者和高血压受试者的风险倍增效应。红细胞叶酸，钴胺素，磷酸吡哆醛，所有这些调节同型半胱氨酸代谢，总同型半胱氨酸水平呈负相关。与不服用维生素补充剂的人相比，服用这种维生素的少数受试者似乎患血管疾病的风险大大降低，其中一部分可归因于血浆同型半胱氨酸水平较低。血浆总同型半胱氨酸水平升高是血管疾病的独立危险因素，与吸烟或高脂血症相似。它大大增加了与吸烟和高血压相关的风险。现在是时候进行随机对照试验的影响，维生素，降低血浆同型半胱氨酸水平对血管疾病的风险。
Context.-Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear.Objective.-To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors.Design.-Case-control study.Setting.-Nineteen centers in 9 European countries.Patients.-A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years.Measurements.-Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured.Results.-The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels.Conclusions.-An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.