Graham I M, Daly L E, Refsum H M, Robinson K, Brattström L E, Ueland P M, Palma-Reis R J, Boers G H, Sheahan R G, Israelsson B, Uiterwaal C S, Meleady R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht J C, de Valk H W, Sales Lúis A C, Parrot-Rouland F M, Tan K S, Higgins I, Garcon D, Andria G
Department of Cardiology, Adelaide Hospital, Trinity College, Dublin, Ireland.
JAMA. 1997 Jun 11;277(22):1775-81. doi: 10.1001/jama.1997.03540460039030.
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.
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.
Case-control study.
Nineteen centers in 9 European countries.
A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years.
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.
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.
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.
血浆同型半胱氨酸水平升高是动脉粥样硬化性血管疾病的已知危险因素，但这种关联的强度以及血浆同型半胱氨酸与其他危险因素之间的相互作用尚不清楚。
确定与血浆同型半胱氨酸水平升高相关的血管疾病风险程度，并研究血浆同型半胱氨酸水平升高与传统危险因素之间的相互作用。
病例对照研究。
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、脑和外周血管疾病）患者以及800名60岁以下的对照者，男女均有。
在受试者空腹时以及进行标准化甲硫氨酸负荷试验后测量血浆总同型半胱氨酸水平，该试验包括每千克体重给予100mg甲硫氨酸，以刺激负责同型半胱氨酸不可逆降解的代谢途径。同时还测量血浆钴胺素、磷酸吡哆醛、红细胞叶酸、血清胆固醇、吸烟情况和血压。
与对照者空腹总同型半胱氨酸分布最低的五分之四相比，最高的五分之一人群患血管疾病的相对风险为2.2（95%置信区间为1.6 - 2.9）。甲硫氨酸负荷试验又识别出另外27%的高危病例。观察到总同型半胱氨酸水平与风险之间存在剂量反应关系。该风险与其他危险因素的风险相似且相互独立，但同型半胱氨酸与这些危险因素之间存在相互作用；对于男女合计而言，空腹同型半胱氨酸水平升高对吸烟者和高血压患者的风险显示出超过相乘的效应。红细胞叶酸、钴胺素和磷酸吡哆醛均调节同型半胱氨酸代谢，它们与总同型半胱氨酸水平呈负相关。与未服用维生素补充剂的人相比，少数服用此类维生素的受试者患血管疾病的风险似乎显著较低，其中一部分原因是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赋予血管疾病独立风险，与吸烟或高脂血症的风险相似。它有力地增加了与吸烟和高血压相关的风险。是时候开展关于降低血浆同型半胱氨酸水平的维生素对血管疾病风险影响的随机对照试验了。
