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

因为患有罕见的家族性同型半胱氨酸尿症的患者 凝血因子V莱顿增加静脉血栓栓塞症的发生率 (VTE)，我们假设了适度的相互关系 高同型球蛋白(E)血症、因子V莱顿与静脉血栓形成风险 普通人口。在一个庞大的预期队列中，我们确定 基线总同型半胱氨酸水平与凝血因子V Leiden突变 145名最初健康的男性的血液样本，这些人后来 在646名仍未患血管疾病的男性中， 在10年的随访期内。高同型(E)血症定义为 作为总同型半胱氨酸水平高于第95个百分位数(17.25mol/L)。 与总同型半胱氨酸水平正常的男性相比， 高同型球蛋白(E)血症不会增加任何VTE的风险，但在 特发性静脉血栓形成的风险增加(相对风险[RR]=3.4，P=0.002)。 与没有莱顿突变的男性相比，那些有莱顿突变的男性 发生任何VTE的风险也增加(RR=2.3，P=0.005) 特发性室上性心动过速(RR=3.6，P=0.002)。与那些既没有钱也没有钱的男人相比 异常情况下，患有这两种疾病的人增加了10倍 对特发性静脉血栓形成的风险(RR=21.8，P=.0004)。看起来很健康的男人 伴发高同型(E)贫血和Leiden突变 极大地增加了未来发生VTE的风险，特别是 这些事件被认为是特发性的。在这些数据中，VTE的风险 在受双重影响的个体中的比例远远大于 单独与任何一种异常相关的个体风险。

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.