HYPERHOMOCYSTEINEMIA - AN INDEPENDENT RISK FACTOR FOR VASCULAR-DISEASE
HYPERHOMOCYSTEINEMIA - AN INDEPENDENT RISK FACTOR FOR VASCULAR-DISEASE
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DOI：
10.1056/nejm199104253241701
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发表时间：
1991-04-25
影响因子：
158.5
通讯作者：
GRAHAM, I
中科院分区：
文献类型：
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作者：
CLARKE, R;DALY, L;GRAHAM, I
背景 甲硫氨酸代谢受损引起的高同型半胱氨酸血症，可能通常是由于胱硫醚β-合酶缺乏，与早发性脑、外周和可能的冠状血管疾病有关。 这种关联的强度及其与其他心血管疾病风险因素的独立性都是不确定的。 我们研究了杂合型胱硫醚β-合酶缺陷在多大程度上可以解释这种关联。 我们首先建立了一个高同型半胱氨酸血症的诊断标准，通过比较25例同型半胱氨酸β-合酶缺陷的专性杂合子（已知其子女是同型胱氨酸尿症的纯合子，由于这种酶缺陷）与27例无关的年龄和性别匹配的正常受试者在标准甲硫氨酸负荷试验后的同型半胱氨酸峰值血清水平。 24.0 μ mol/L或更高的水平在区分两组时具有92%的敏感性和100%的特异性。 然后将这些正常受试者的血清同型半胱氨酸峰值水平与123例在55岁之前被诊断为血管疾病的患者进行比较。 高同型半胱氨酸血症在38例脑血管疾病患者中有16例（42%），25例外周血管疾病患者中有7例（28%），60例冠状动脉疾病患者中有18例（30%），但在27名正常受试者中没有检测到。 在调整了传统危险因素的影响后，与正常受试者相比，高同型半胱氨酸血症患者血管疾病的比值比的95%置信下限为3.2。 血管疾病患者血清同型半胱氨酸峰值几何平均值是正常人的1.33倍（P = 0.002）。 23例高同型半胱氨酸血症的血管疾病患者中有18例证实存在胱硫醚β-合酶缺陷。 高同型半胱氨酸血症是血管疾病（包括冠心病）的独立危险因素，在大多数情况下可能是由于胱硫醚β-合酶缺乏所致。
Background. Hyperhomocysteinemia arising from impaired methionine metabolism, probably usually due to a deficiency of cystathionine beta-synthase, is associated with premature cerebral, peripheral, and possibly coronary vascular disease. Both the strength of this association and its independence of other risk factors for cardiovascular disease are uncertain. We studied the extent to which the association could be explained by heterozygous cystathionine beta-synthase deficiency.Methods. We first established a diagnostic criterion for hyperhomocysteinemia by comparing peak serum levels of homocysteine after a standard methionine-loading test in 25 obligate heterozygotes with respect to cystathionine beta-synthase deficiency (whose children were known to be homozygous for homocystinuria due to this enzyme defect) with the levels in 27 unrelated age- and sex-matched normal subjects. A level of 24.0-mu-mol per liter or more was 92 percent sensitive and 100 percent specific in distinguishing the two groups. The peak serum homocysteine levels in these normal subjects were then compared with those in 123 patients whose vascular disease had been diagnosed before they were 55 years of age.Results. Hyperhomocysteinemia was detected in 16 of 38 patients with cerebrovascular disease (42 percent), 7 of 25 with peripheral vascular disease (28 percent), and 18 of 60 with coronary vascular disease (30 percent), but in none of the 27 normal subjects. After adjustment for the effects of conventional risk factors, the lower 95 percent confidence limit for the odds ratio for vascular disease among the patients with hyperhomocysteinemia, as compared with the normal subjects, was 3.2. The geometric-mean peak serum homocysteine level was 1.33 times higher in the patients with vascular disease than in the normal subjects (P = 0.002). The presence of cystathionine beta-synthase deficiency was confirmed in 18 of 23 patients with vascular disease who had hyperhomocysteinemia.Conclusions. Hyperhomocysteinemia is an independent risk factor for vascular disease, including coronary disease, and in most instances is probably due to cystathionine beta-synthase deficiency.