Toyomasu Kenta, Adachi Hisashi, Enomoto Mika, Fukami Ako, Nakamura Sachiko, Nohara Yume, Morikawa Nagisa, Sakaue Akiko, Hamamura Hitoshi, Yamamoto Maki, Fukumoto Yoshihiro
Department of Internal Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine, Kurume, Japan.
Department of Internal Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine, Kurume, Japan; Department of Community Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
J Cardiol. 2021 Aug;78(2):129-135. doi: 10.1016/j.jjcc.2021.01.011. Epub 2021 Feb 4.
Both homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) induce endothelial dysfunction. However, the impact of both elevations on all-cause death is not known. We investigated the association between elevations of Hcy or ADMA and all-cause death in a general population.
A total of 517 subjects (224 men, 293 women; mean age, 62.8 years) were recruited from a population-based survey in 1999 in Tanushimaru, and we measured fasting plasma Hcy and ADMA levels. We followed them up for over 20 years and examined the effect on mortality using Cox proportional hazard regression model.
The mean follow-up years were 17.7 (1.8-20.8). In this period, 182 subjects have died (35.2%). The correlation between Hcy and ADMA was high (r=0.194; p<0.001). With Cox regression analysis after adjustments for age and sex, elevated log transformed Hcy levels were significantly associated with all-cause death (p=0.028). When Hcy and ADMA levels were divided into quintiles, the hierarchical model showed the synergistic effect of Hcy and ADMA on all-cause death.
This is the first report that we have measured Hcy and ADMA levels simultaneously in this community-dwelling Japanese, and we demonstrated that combined elevations of Hcy and ADMA had big impact on all-cause death in this epidemiological study.
同型半胱氨酸（Hcy）和不对称二甲基精氨酸（ADMA）均可导致内皮功能障碍。然而，两者升高对全因死亡的影响尚不清楚。我们调查了普通人群中Hcy或ADMA升高与全因死亡之间的关联。
1999年从种子丸市基于人群的调查中招募了517名受试者（224名男性，293名女性；平均年龄62.8岁），并测量了空腹血浆Hcy和ADMA水平。我们对他们进行了20多年的随访，并使用Cox比例风险回归模型研究了对死亡率的影响。
平均随访年限为17.7年（1.8 - 20.8年）。在此期间，182名受试者死亡（35.2%）。Hcy与ADMA之间的相关性较高（r = 0.194；p < 0.001）。在对年龄和性别进行调整后的Cox回归分析中，对数转换后的Hcy水平升高与全因死亡显著相关（p = 0.028）。当将Hcy和ADMA水平分为五分位数时，分层模型显示Hcy和ADMA对全因死亡具有协同作用。
这是我们首次在这个日本社区居住人群中同时测量Hcy和ADMA水平，并且我们在这项流行病学研究中证明，Hcy和ADMA的联合升高对全因死亡有很大影响。
