From the Department of Internal Medicine, Division of Cardiology (M.O.G., C.R.A., A.K., J.A.d.L., D.K.M.) and the Donald W. Reynolds Cardiovascular Clinical Research Center (C.R.A., A.K., J.A.d.L., D.K.M.), University of Texas Southwestern Medical Center, Dallas, TX; Institute of Clinical Pharmacology and Toxicology and Cardiovascular Research Center (N.L., E.S., M.A., D.A., R.H.B.), University Medical Center Hamburg-Eppendorf, and German Center for Cardiovascular Research, Partner Site Hamburg/Lübeck/Kiel (E.S., D.A., R.H.B.), Hamburg, Germany; and Leeds Institute of Genetics, Health and Therapeutics, Leeds, United Kingdom (P.J.G.).
Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2682-8. doi: 10.1161/ATVBAHA.113.301219. Epub 2013 Sep 5.
Increased asymmetrical dimethylarginine (ADMA), a NO synthase inhibitor, and its congener symmetrical dimethylarginine (SDMA), predict cardiovascular and all-cause mortality in at-risk populations. Their prognostic value in the general population remains uncertain. We investigated the correlations of SDMA and ADMA with atherosclerosis and cardiovascular/all-cause mortality in the Dallas Heart Study, a multiethnic probability-based cohort aged 30 to 65 years.
SDMA and ADMA were measured by liquid chromatography-tandem mass-spectrometry (n=3523), coronary artery calcium by electron-beam computed tomography, and abdominal aortic wall thickness by MRI. In unadjusted analyses, categories of increasing SDMA and ADMA were associated with higher prevalence of cardiovascular risk factors, increased risk markers, and all-cause and cardiovascular mortality (median follow-up, 7.4 years). After adjustment for age, sex, and race, traditional cardiovascular risk factors, and renal function, SDMA and ADMA analyzed as continuous variables were associated with coronary artery calcium >10, but only SDMA was associated with abdominal aortic wall thickness. SDMA, but not ADMA, was associated with cardiovascular mortality (hazard ratio per log unit change, 3.36 [95% confidence interval, 1.49-7.59]; P=0.004). SDMA and ADMA were both associated with all-cause mortality, but after further adjustment for N-terminal pro-brain-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin T, only SDMA was associated with all-cause mortality (hazard ratio per log unit change, 1.86 [95% confidence interval, 1.04-3.30]; P=0.01).
SDMA, but not ADMA, was an independent predictor of all-cause and cardiovascular mortality in a large multiethnic population-based cohort.
作为一氧化氮合酶抑制剂的非对称性二甲基精氨酸（ADMA）及其同系物对称性二甲基精氨酸（SDMA）水平升高，可预测高危人群的心血管疾病和全因死亡率。但其在普通人群中的预后价值尚不确定。我们在达拉斯心脏研究中对此进行了研究，该研究是一项多民族基于概率的队列研究，纳入年龄在 30 至 65 岁之间的人群，旨在探讨 SDMA 和 ADMA 与动脉粥样硬化及心血管疾病/全因死亡率之间的相关性。
通过液相色谱-串联质谱法（n=3523）检测 SDMA 和 ADMA，通过电子束计算机断层扫描检测冠状动脉钙，通过 MRI 检测腹主动脉壁厚度。在未经调整的分析中，SDMA 和 ADMA 水平递增的各分类与心血管危险因素、风险标志物及全因和心血管死亡率增加相关（中位随访时间为 7.4 年）。在校正年龄、性别和种族、传统心血管危险因素及肾功能后，SDMA 和 ADMA 作为连续变量进行分析时，与冠状动脉钙>10 相关，但仅与 SDMA 与腹主动脉壁厚度相关。SDMA 与心血管死亡率相关（每单位对数变化的危险比，3.36[95%置信区间，1.49-7.59]；P=0.004），但 ADMA 与心血管死亡率无关。SDMA 和 ADMA 均与全因死亡率相关，但在进一步校正 N 末端脑利钠肽前体、高敏 C 反应蛋白和高敏心肌肌钙蛋白 T 后，仅 SDMA 与全因死亡率相关（每单位对数变化的危险比，1.86[95%置信区间，1.04-3.30]；P=0.01）。
在一个大型多民族基于人群的队列中，SDMA 而非 ADMA 是全因和心血管死亡率的独立预测因子。
