McQuillan B M, Beilby J P, Nidorf M, Thompson P L, Hung J
Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia.
Circulation. 1999 May 11;99(18):2383-8. doi: 10.1161/01.cir.99.18.2383.
Hyperhomocysteinemia has been identified as a potential risk factor for atherosclerosis. This study examined whether a modest elevation of plasma total homocysteine (tHcy) was an independent risk factor for increased carotid artery intimal-medial wall thickness (IMT) and focal plaque formation in a large, randomly selected community population. We also examined whether vitamin cofactors and the C677T genetic mutation of the methylenetetrahydrofolate reductase (MTHFR) enzyme were major contributors to elevated plasma tHcy and carotid vascular disease.
In 1111 subjects (558 men, 553 women) 52+/-13 years old (mean+/-SD; range, 27 to 77 years) recruited from a random electoral roll survey, we measured fasting tHcy and performed bilateral carotid B-mode ultrasound. For the total population, mean tHcy was 12.1+/-4.0 micromol/L. Plasma tHcy levels were correlated with IMT (Spearman rank rs=0.31, P=0.0001). After adjustment for age, sex, and other conventional risk factors, subjects in the highest versus the lowest quartile of tHcy had an odds ratio of 2.60 (95% CI, 1.51 to 4.45) for increased IMT and 1.76 (95% CI, 1.10 to 2.82) for plaque. Serum and dietary folate levels and the C677T mutation in MTHFR were independent determinants of tHcy (all P=0.0001). The mutant homozygotes (10% of the population) had higher mean tHcy than heterozygotes or those without the mutation (14.2 versus 12.3 versus 11.6 micromol/L, respectively, P=0.0001). The inverse association of folate levels with tHcy was steeper in the mutant homozygotes. Despite this, the C677T MTHFR mutation was not independently predictive of increased carotid IMT or plaque formation.
Mild hyperhomocysteinemia is an independent risk factor for increased carotid artery wall thickness and plaque formation in a general population. Lower levels of dietary folate intake and the C677T mutation in MTHFR are important causes of mild hyperhomocysteinemia and may therefore contribute to vascular disease in the community.
高同型半胱氨酸血症已被确认为动脉粥样硬化的潜在危险因素。本研究调查了血浆总同型半胱氨酸（tHcy）的适度升高是否是一个大型随机选择社区人群中颈动脉内膜中层厚度（IMT）增加和局灶性斑块形成的独立危险因素。我们还研究了维生素辅助因子和亚甲基四氢叶酸还原酶（MTHFR）酶的C677T基因突变是否是血浆tHcy升高和颈动脉血管疾病的主要促成因素。
在从随机选民名册调查中招募的1111名年龄为52±13岁（平均±标准差；范围27至77岁）的受试者（558名男性，553名女性）中，我们测量了空腹tHcy并进行了双侧颈动脉B型超声检查。对于总体人群，平均tHcy为12.1±4.0μmol/L。血浆tHcy水平与IMT相关（Spearman等级rs = 0.31，P = 0.0001）。在调整年龄、性别和其他传统危险因素后，tHcy最高四分位数与最低四分位数的受试者IMT增加的优势比为2.60（95%CI，1.51至4.45），斑块的优势比为1.76（95%CI，1.10至2.82）。血清和膳食叶酸水平以及MTHFR中的C677T突变是tHcy的独立决定因素（所有P = 0.0001）。突变纯合子（占人群的10%）的平均tHcy高于杂合子或无突变者（分别为14.2、12.3和11.6μmol/L，P = 0.0001）。在突变纯合子中，叶酸水平与tHcy的负相关更陡峭。尽管如此，C677T MTHFR突变并不能独立预测颈动脉IMT增加或斑块形成。
轻度高同型半胱氨酸血症是普通人群中颈动脉壁厚度增加和斑块形成的独立危险因素。膳食叶酸摄入水平较低和MTHFR中的C677T突变是轻度高同型半胱氨酸血症的重要原因，因此可能导致社区中的血管疾病。
