HYPER HOMOCYST(E)INEMIA, FACTOR V LEIDEN & RISK OF FUTURE VENOUS THROMBOEMBOLISM

因为患有罕见的家族性同型胱氨酸尿症的患者， 凝血因子V莱顿有静脉血栓栓塞症的发病率增加 (VTE)，我们假设适度的 高同型半胱氨酸血症、凝血因子V Leiden和静脉血栓栓塞风险 一般人口。 在一个大型前瞻性队列中，我们确定 基线总同型半胱氨酸水平和凝血因子V Leiden突变 来自145名最初健康的男性的血液样本， 在646名无血管疾病的男性中， 在10年的随访期内。 高同型半胱氨酸血症定义为 总同型半胱氨酸水平高于第95百分位数（17.25 mol/L）。 与总同型半胱氨酸水平正常的男性相比， 高同型半胱氨酸血症没有增加任何静脉血栓栓塞的风险，但在 特发性VTE风险增加（相对风险[RR]=3.4，P=.002）。 与没有莱顿突变的男性相比， 发生任何静脉血栓栓塞的风险也增加（RR=2.3，P=.005） 特发性VTE（RR=3.6，P=.0002）。 与两者都没有的男性相比 异常，受这两种疾病影响的人有10倍的增加， 发生特发性VTE的风险（RR=21.8，P=.0004）。 显然健康的男性 高同型半胱氨酸（e）血症和Leiden突变并存的患者， 大大增加了发展未来VTE的风险，特别是 这些事件被视为特发性。 在这些数据中，静脉血栓栓塞的风险 在双重影响的个人中， 与任一异常单独相关的个体风险。

Because patients with rare familial homocystinuria who also carry factor V Leiden have an increased incidence of venous thromboembolism (VTE), we hypothesized an interrelation of moderate hyperhomocyst(e)inemia, factor V Leiden, and risk of VTE in the general population. In a large prospective cohort, we determined total homocysteine level and factor V Leiden mutation in baseline blood samples from 145 initially healthy men who subsequently developed VTE and among 646 men who remained free of vascular disease during a 10-year follow-up period. Hyperhomocyst(e)inemia was defined as a total homocysteine level above the 95th percentile (17.25 mol/L). Compared with men with normal total homocysteine levels, those with hyperhomocyst(e)inemia had no increase in risk of any VTE but were at increased risk of idiopathic VTE (relative risk [RR]=3.4, P=.002). Compared with men without the Leiden mutation, those with the mutation were at increased risk of developing any VTE (RR=2.3, P=.005) as well as idiopathic VTE (RR=3.6, P=.0002). Compared with men with neither abnormality, those affected by both disorders had a 10-fold increase in risk of idiopathic VTE (RR=21.8, P=.0004). Apparently healthy men with coexistent hyperhomocyst(e)inemia and Leiden mutation are at a substantially increased risk of developing future VTE's, particularly those events considered idiopathic. In these data, the risk of VTE among doubly affected individuals was far greater than the sum of the individual risks associated with either abnormality alone.