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目的:血管发育异常、损伤修复能力下降等将影响血管的正常结构与功能,与心脑血管疾病的发生及预后密切相关。本文探讨血管内皮细胞生长因子受体(VEGFR-2)基因编码区变异Val297Ile对脑卒中复发风险及心血管病死率的影响。方法:自2000-2001年在全国7个临床中心入选1849例脑卒中患者(35～74岁),进行前瞻性随访4.5年(中位数,范围0.1～6.0年),收集脑卒中复发和死亡事件。Cox生存回归模型分析基因变异与脑卒中复发及病死率的关系。结果:长期随访过程中,355例发生脑卒中复发事件,180例死于心血管病事件。携带297Ile等位基因的脑卒中患者4.5年累积复发率为24.3%,心血管病死率为13.6%,显著高于297Val携带者(分别为17.4%和8.4%)。Cox生存回归模型校正了年龄、性别和其他心血管危险因素后,297Ile等位基因与增加的脑卒中复发风险(RR:1.40,95%CI1.12～1.75;P=0.003)和心血管病死率(RR:1.64,95%CI1.21～2.23;P=0.002)相关。结论:VEGFR-2基因编码区变异297Ile是一个与脑卒中高复发风险和心血管病死率相关的新的预测因子,其机制与受损血管内皮的修复能力下降有关。
OBJECTIVE: The abnormal development of blood vessels and the impairment of injury repair will affect the normal structure and function of blood vessels, which are closely related to the occurrence and prognosis of cardiovascular and cerebrovascular diseases. This article investigates the effect of Val297Ile, a mutation in the coding region of the vascular endothelial growth factor receptor (VEGFR-2) gene, on the risk of recurrent stroke and cardiovascular mortality. METHODS: A total of 1849 stroke patients (35-74 years) were enrolled in seven clinical centers across the country from 2000-2001 for a prospective follow-up of 4.5 years (median, range, 0.1-6.0 years) to collect for recurrent stroke and death event. Cox regression model was used to analyze the relationship between gene mutation and stroke recurrence and mortality. Results: During the long-term follow-up, 355 patients had recurrent stroke and 180 patients died of cardiovascular disease. Stroke patients with the 297Ile allele had a cumulative recurrence rate of 4.5% at 24.5% and a cardiovascular mortality rate of 13.6%, significantly higher than 297Val carriers (17.4% and 8.4%, respectively). The Cox survival regression model adjusted for 297 Ile alleles with an increased risk of recurrent stroke (RR: 1.40, 95% CI 1.12 to 1.75; P = 0.003) and cardiovascular mortality after adjusting for age, sex and other cardiovascular risk factors (RR: 1.64, 95% CI 1.21-2.23; P = 0.002). CONCLUSIONS: Variation in the coding region of VEGFR-2 297Ile is a new predictor of the high risk of recurrent stroke and cardiovascular mortality with a mechanism that is associated with a decreased ability to repair the damaged vascular endothelium.