Division of Cardiology, University of California, Los Angeles, Los Angeles, California.
Division of Cardiovascular Medicine, Stanford University, Stanford, California.
Am J Cardiol. 2018 Nov 15;122(10):1707-1711. doi: 10.1016/j.amjcard.2018.07.048. Epub 2018 Aug 21.
Asymmetric dimethylarginine (ADMA) is a key mediator of vascular homeostasis and an independent predictor of the development of accelerated cardiac allograft vasculopathy after heart transplantation. However, its association with clinical outcomes in heart transplant recipients has not been described. Plasma levels of ADMA were assayed within 8 weeks following transplantation (baseline) using a competitive enzyme-linked immunosorbent assay. The primary end point was the composite of nonfatal myocardial infarction, percutaneous coronary intervention, retransplantation, or death at 5-year follow-up. Kaplan-Meier curves were generated to assess the association between baseline ADMA levels (stratified at 0.70 µM, a previously established cutoff) and cumulative event-free survival. Multivariate Cox regression was performed to adjust for other candidate predictors. In 69 heart transplant recipients at Stanford, the primary end point occurred in 11 patients (16%)-4 percutaneous coronary intervention, 1 retransplant, and 6 deaths-during 5-years follow-up. Patients with baseline ADMA ≥0.70 µM had lower cumulative 5-year event-free survival (77% vs 93%, p = 0.059). In multivariate Cox analysis, baseline ADMA was the only significant predictor of the primary end point (hazard ratio 1.33, 95% confidence interval 1.03 to 1.72 per 0.1 µM; p = 0.031). This association remained significant even after restricting the end point to death or retransplantation (hazard ratio 1.48, 95% confidence interval 1.12 to 1.97 per 0.1 µM; p = 0.006). In conclusion, elevated baseline plasma levels of ADMA independently predicted 5-year clinical outcomes after heart transplantation, suggesting that ADMA has potential prognostic value in the heart transplant arena.
不对称二甲基精氨酸（ADMA）是血管内稳态的关键介质，也是心脏移植后加速心脏同种异体移植血管病发展的独立预测因子。然而，其与心脏移植受者临床结局的关系尚未描述。ADMA 水平使用竞争性酶联免疫吸附试验在移植后 8 周内（基线）进行测定。主要终点是 5 年随访时非致命性心肌梗死、经皮冠状动脉介入治疗、再次移植或死亡的复合终点。生成 Kaplan-Meier 曲线以评估基线 ADMA 水平（在 0.70 µM 处分层，这是以前建立的截止值）与累积无事件生存之间的关系。进行多变量 Cox 回归以调整其他候选预测因子。在斯坦福的 69 名心脏移植受者中，11 名患者（16%）在 5 年随访期间发生了主要终点事件-4 例经皮冠状动脉介入治疗、1 例再次移植和 6 例死亡。基线 ADMA≥0.70 µM 的患者累积 5 年无事件生存率较低（77%对 93%，p=0.059）。多变量 Cox 分析中，基线 ADMA 是主要终点的唯一显著预测因子（风险比 1.33，95%置信区间 1.03 至 1.72/每 0.1 µM；p=0.031）。即使将终点限制为死亡或再次移植，这种关联仍然显著（风险比 1.48，95%置信区间 1.12 至 1.97/每 0.1 µM；p=0.006）。总之，基线血浆 ADMA 水平升高独立预测心脏移植后 5 年临床结局，表明 ADMA 在心脏移植领域具有潜在的预后价值。
