Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, 2820, Gentofte, Denmark.
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
Cardiovasc Diabetol. 2017 Jul 11;16(1):88. doi: 10.1186/s12933-017-0569-8.
BACKGROUND: To evaluate symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) as risk markers of cardiovascular disease, all-cause mortality and deterioration in renal function in a well characterised type 2 diabetic population with microalbuminuria and without symptoms of coronary artery disease. METHODS: 200 participants followed for 6.1 years. SDMA and ADMA were measured at baseline. Endpoints included (1) composite cardiovascular endpoint (n = 40); (2) all-cause mortality (n = 26); and (3) decline in eGFR of >30% (n = 42). Cox models were unadjusted and adjusted for traditional risk factors (sex, age, systolic blood pressure, LDL-cholesterol, smoking, HbA, creatinine and urinary albumin excretion rate). To assess if SDMA or ADMA improved risk prediction beyond traditional risk factors we calculated c statistics and relative integrated discrimination improvement (rIDI). C statistic (area under the curve) quantifies the model's improved ability to discriminate events from non-events. rIDI quantifies the increase in separation of events and non-events on a relative scale. RESULTS: Higher SDMA was associated with increased risk of all three endpoints (unadjusted: p ≤ 0.001; adjusted: p ≤ 0.02). Higher ADMA was associated with all-cause mortality (unadjusted: p = 0.002; adjusted: p = 0.006), but not cardiovascular disease or decline in eGFR (p ≥ 0.29).The c statistic was not significant for any of the endpoints for either SDMA or ADMA (p ≥ 0.10). The rIDI for SDMA was 15.0% (p = 0.081) for the cardiovascular endpoint, 52.5% (p = 0.025) for all-cause mortality and 48.8% (p = 0.007) for decline in eGFR; for ADMA the rIDI was 49.1% (p = 0.017) for all-cause mortality. CONCLUSION: In persons with type 2 diabetes and microalbuminuria higher SDMA was associated with incident cardiovascular disease, all-cause mortality and deterioration in renal function. Higher ADMA was associated with all-cause mortality. SDMA and ADMA significantly improved risk prediction for all-cause mortality, and SDMA for deterioration in renal function beyond traditional risk factors.
背景：为了评估对称二甲基精氨酸（SDMA）和非对称二甲基精氨酸（ADMA）作为心血管疾病、全因死亡率和肾功能恶化的风险标志物，我们在患有微量白蛋白尿且无冠心病症状的 2 型糖尿病患者中进行了一项特征明确的研究。
方法：200 名参与者随访 6.1 年。在基线时测量了 SDMA 和 ADMA。终点包括（1）复合心血管终点（n=40）；（2）全因死亡率（n=26）；（3）eGFR 下降>30%（n=42）。Cox 模型未调整，调整了传统危险因素（性别、年龄、收缩压、LDL-胆固醇、吸烟、HbA、肌酐和尿白蛋白排泄率）。为了评估 SDMA 或 ADMA 是否能改善传统危险因素以外的风险预测，我们计算了 C 统计量和相对综合判别改善（rIDI）。C 统计量（曲线下面积）量化了模型对事件和非事件的区分能力的提高。rIDI 量化了事件和非事件在相对尺度上的分离程度的增加。
结果：较高的 SDMA 与所有三个终点的风险增加相关（未调整：p≤0.001；调整：p≤0.02）。较高的 ADMA 与全因死亡率相关（未调整：p=0.002；调整：p=0.006），但与心血管疾病或 eGFR 下降无关（p≥0.29）。SDMA 或 ADMA 对任何终点的 C 统计量均无统计学意义（p≥0.10）。SDMA 的 rIDI 为心血管终点的 15.0%（p=0.081），全因死亡率的 52.5%（p=0.025），eGFR 下降的 48.8%（p=0.007）；ADMA 的 rIDI 为全因死亡率的 49.1%（p=0.017）。
结论：在 2 型糖尿病合并微量白蛋白尿的患者中，较高的 SDMA 与心血管疾病、全因死亡率和肾功能恶化的发生有关。较高的 ADMA 与全因死亡率有关。SDMA 和 ADMA 显著改善了全因死亡率的风险预测，SDMA 改善了肾功能恶化的风险预测，优于传统危险因素。
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