Department of Surgery, Centre for Surgical Science, Zealand University Hospital, Køge, Denmark.
Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Herlev, Denmark.
J Pineal Res. 2019 Oct;67(3):e12600. doi: 10.1111/jpi.12600. Epub 2019 Aug 22.
Endothelial dysfunction (ED) precedes acute coronary syndrome. Oxidative stress results in ED but is reversible. Melatonin is aside from being a circadian hormone, also an antioxidant. The aim of this study was to investigate whether 25 mg melatonin administered for twelve weeks following acute coronary syndrome (ACS) could improve ED. In this placebo-controlled randomized trial, ED was measured as reactive hyperemia index (RHI) at baseline, day 14, and day 84. The effect was assessed using a generalized estimating equation adjusted for the baseline RHI. As secondary outcome, the concentrations of three biomarkers were measured: l-arginine, asymmetric dimethylarginine, and uric acid. Thirty-one patients were included in the study. The intention-to-treat analysis of the primary outcome had 26 patients due to missing data. The estimated marginal mean difference in RHI at day 14 and day 84 between the groups was 0.15 (95% CI: 0.29-0.01, P = .039) in favor of the placebo group. No significant differences in the biomarker concentrations were found. Melatonin treatment after ACS did not improve but may have aggravated ED. The significant difference between groups was in favor of placebo, but this might be due to the effect of missing data or uneven distribution of comorbidities.
内皮功能障碍 (ED) 先于急性冠脉综合征。氧化应激导致 ED，但可逆转。褪黑素除了作为一种昼夜节律激素外，还是一种抗氧化剂。本研究旨在探讨急性冠脉综合征 (ACS) 后接受 25mg 褪黑素治疗 12 周是否能改善 ED。在这项安慰剂对照随机试验中，ED 通过基线、第 14 天和第 84 天的反应性充血指数 (RHI) 来测量。使用调整基线 RHI 的广义估计方程评估效果。作为次要结局，测量了三种生物标志物的浓度：l-精氨酸、非对称二甲基精氨酸和尿酸。31 名患者纳入本研究。由于数据缺失，意向治疗分析中主要结局有 26 名患者。两组在第 14 天和第 84 天的 RHI 估计边缘均值差异为 0.15（95%CI：0.29-0.01，P=0.039），有利于安慰剂组。生物标志物浓度无显著差异。ACS 后褪黑素治疗并未改善 ED，反而可能加重了 ED。组间的显著差异有利于安慰剂，但这可能是由于缺失数据或合并症分布不均的影响。
