CNR-IBIM, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.
Clin J Am Soc Nephrol. 2011 Jul;6(7):1714-21. doi: 10.2215/CJN.11291210. Epub 2011 Jun 3.
Endothelial dysfunction as assessed by asymmetric dimethylarginine (ADMA) and inflammation has been consistently linked to atherosclerosis, death, and cardiovascular (CV) events in ESRD patients. Inflammation amplifies the effect of ADMA on the severity of atherosclerosis in ESRD patients, but it is still unknown whether inflammation and ADMA interact in the high risk of death and CV events in this population.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cohort of 225 hemodialysis patients, we investigated the interaction between inflammatory biomarkers (C-reactive protein and IL-6) and ADMA as predictors of death and CV events over an extended follow-up (13 years).
During follow-up, 160 patients died, and 123 had CV events. With crude and multiple Cox regression analyses, an interaction was found between inflammation biomarkers and ADMA for explaining death and CV events in ESRD patients. The adjusted hazard ratios (HRs) for death (HR, 2.18; 95% confidence interval [CI], 1.34 to 3.54) and CV outcomes (HR, 2.59; 95% CI, 1.47 to 4.55) of patients with C-reactive protein and ADMA above the median were higher than expected in the absence of interaction under the additive model (1.15 and 1.97, respectively) and significantly higher than in patients with only one biomarker above the median. Data analyses carried out by stratifying patients according to IL-6 provided similar results.
These data support the hypothesis that inflammation amplifies the risk of death and CV events associated with high ADMA levels in ESRD. These analyses further emphasize the need for intervention studies to attenuate inflammation and high ADMA levels in this population.
不对称二甲基精氨酸（ADMA）和炎症引起的内皮功能障碍与终末期肾病（ESRD）患者的动脉粥样硬化、死亡和心血管（CV）事件密切相关。在 ESRD 患者中，炎症放大了 ADMA 对动脉粥样硬化严重程度的影响，但尚不清楚炎症和 ADMA 是否在该人群的高死亡和 CV 事件风险中相互作用。
设计、设置、参与者和测量：在一项 225 名血液透析患者的队列研究中，我们研究了炎症生物标志物（C 反应蛋白和 IL-6）和 ADMA 之间的相互作用，以预测该人群在延长随访期间（13 年）的死亡和 CV 事件。
在随访期间，160 名患者死亡，123 名患者发生 CV 事件。通过粗 Cox 回归和多因素 Cox 回归分析，发现炎症生物标志物和 ADMA 之间存在交互作用，可以解释 ESRD 患者的死亡和 CV 事件。调整后的死亡风险比（HR）（HR，2.18；95%置信区间[CI]，1.34 至 3.54）和 CV 结局（HR，2.59；95%CI，1.47 至 4.55），对于 C 反应蛋白和 ADMA 均高于中位数的患者，在无交互作用的情况下，高于相加模型（分别为 1.15 和 1.97），且明显高于仅有一种生物标志物高于中位数的患者。根据 IL-6 对患者进行分层后进行数据分析，得到了类似的结果。
这些数据支持这样一种假设，即炎症放大了与 ESRD 患者高水平 ADMA 相关的死亡和 CV 事件风险。这些分析进一步强调了在该人群中进行干预研究以减轻炎症和高水平 ADMA 的必要性。
