Division of Cardiology, Department of Internal Medicine II, Vienna General Hospital, Medical University of Vienna, Vienna, Austria; Pulmonary Institute, Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Division of Cardiology, Department of Internal Medicine II, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
JACC Heart Fail. 2024 Jun;12(6):1089-1097. doi: 10.1016/j.jchf.2024.02.013. Epub 2024 Apr 3.
Plasma asymmetric dimethylarginine (ADMA) is elevated in pulmonary arterial hypertension (PAH) and is associated with unfavorable outcomes.
The aim of this study was to assess changes in ADMA plasma levels for monitoring disease progression and outcomes during PAH-specific therapy.
ADMA was measured at baseline and after at least 6 months of follow-up using enzyme-linked immunosorbent assay and high-performance liquid chromatography. Changes in ADMA were analyzed in relation to changes in established PAH markers, including hemodynamic status, N-terminal pro-brain natriuretic peptide (NT-proBNP) and risk assessment scores. Impact on survival was assessed using Kaplan-Meier curves and Cox proportional hazards models.
Between 2008 and 2019, ADMA samples were collected prospectively from 215 patients with PAH. Change in ADMA plasma level was a predictor of disease progression and survival. ΔADMA (median -0.03 μmol/L; 95% CI: -0.145 to 0.0135) was correlated with change in mean pulmonary arterial pressure (P < 0.005; r = 0.287) but was not significantly correlated with ΔNT-proBNP (P = 0.056; r = 0.135). Patients with decreased ADMA plasma levels at follow-up had better 3-year and 5-year survival rates (88% and 80%, respectively, vs 72% and 53% in those without decreases in ADMA) (P < 0.005; pulmonary hypertension-related mortality or lung transplantation). Patients with decreases in both ADMA and NT-proBNP had better survival rates compared with patients in whom only 1 parameter improved (P < 0.005). ΔADMA was a significant predictor of survival in Cox regression analysis and also when corrected for ΔNT-proBNP (HRs: 1.27 and 1.35, respectively; P < 0.005).
ADMA and NT-proBNP provide synergistic prognostic information for patients with PAH. ADMA could be used as an objective and distinct biomarker for monitoring treatment response in PAH.
血浆不对称二甲基精氨酸（ADMA）在肺动脉高压（PAH）中升高，并与不良结局相关。
本研究旨在评估 ADMA 血浆水平的变化，以监测 PAH 特异性治疗期间疾病的进展和结局。
使用酶联免疫吸附法和高效液相色谱法在基线和至少 6 个月的随访后测量 ADMA。分析 ADMA 的变化与已建立的 PAH 标志物的变化之间的关系，包括血流动力学状态、N 端脑利钠肽前体（NT-proBNP）和风险评估评分。使用 Kaplan-Meier 曲线和 Cox 比例风险模型评估对生存的影响。
2008 年至 2019 年期间，前瞻性收集了 215 例 PAH 患者的 ADMA 样本。ADMA 血浆水平的变化是疾病进展和生存的预测指标。ADMA 的变化量（中位数-0.03μmol/L；95%CI：-0.145 至 0.0135）与平均肺动脉压的变化相关（P<0.005；r=0.287），但与 NT-proBNP 的变化无显著相关性（P=0.056；r=0.135）。随访时 ADMA 血浆水平降低的患者 3 年和 5 年生存率更好（分别为 88%和 80%，而 ADMA 无下降的患者分别为 72%和 53%）（P<0.005；肺动脉高压相关死亡率或肺移植）。与仅 1 个参数改善的患者相比，ADMA 和 NT-proBNP 均降低的患者生存率更高（P<0.005）。在 Cox 回归分析中，ADMA 是生存的显著预测因子，在校正 NT-proBNP 后也是如此（HRs：分别为 1.27 和 1.35；P<0.005）。
ADMA 和 NT-proBNP 为 PAH 患者提供协同的预后信息。ADMA 可作为监测 PAH 治疗反应的客观、独特的生物标志物。
