Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I
Department of Cardiology, Adelaide Hospital, Dublin, Ireland.
N Engl J Med. 1991 Apr 25;324(17):1149-55. doi: 10.1056/NEJM199104253241701.
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.
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 mumol 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.
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.
Hyperhomocysteinemia is an independent risk factor for vascular disease, including coronary disease, and in most instances is probably due to cystathionine beta-synthase deficiency.
甲硫氨酸代谢受损引起的高同型半胱氨酸血症，通常可能是由于胱硫醚β合酶缺乏，与过早发生的脑、外周血管疾病以及可能的冠状动脉疾病相关。这种关联的强度及其与心血管疾病其他危险因素的独立性尚不确定。我们研究了杂合性胱硫醚β合酶缺乏在多大程度上可以解释这种关联。
我们首先通过比较25名胱硫醚β合酶缺乏的纯合子（其子女因该酶缺陷而患同型胱氨酸尿症）在标准甲硫氨酸负荷试验后血清同型半胱氨酸的峰值水平与27名年龄和性别匹配的无关正常受试者的水平，建立了高同型半胱氨酸血症的诊断标准。每升24.0微摩尔或更高的水平在区分两组时敏感性为92%，特异性为100%。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名在55岁之前被诊断患有血管疾病的患者的水平进行比较。
在38例脑血管疾病患者中有16例（42%）检测到高同型半胱氨酸血症，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%），而27名正常受试者中均未检测到。在对传统危险因素的影响进行调整后，与正常受试者相比，高同型半胱氨酸血症患者血管疾病比值比的95%置信下限为3.2。血管疾病患者血清同型半胱氨酸峰值水平的几何平均值比正常受试者高1.33倍（P = 0.002）。在23例患有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合酶缺乏。
高同型半胱氨酸血症是包括冠状动脉疾病在内的血管疾病的独立危险因素，在大多数情况下可能是由于胱硫醚β合酶缺乏所致。
