Cai Zongye, Klein Theo, Geenen Laurie W, Tu Ly, Tian Siyu, van den Bosch Annemien E, de Rijke Yolanda B, Reiss Irwin K M, Boersma Eric, Duncker Dirk J, Boomars Karin A, Guignabert Christophe, Merkus Daphne
Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, 3000 CB Rotterdam, The Netherlands.
J Clin Med. 2020 Apr 25;9(5):1248. doi: 10.3390/jcm9051248.
Exogenous melatonin has been reported to be beneficial in the treatment of pulmonary hypertension (PH) in animal models. Multiple mechanisms are involved, with melatonin exerting anti-oxidant and anti-inflammatory effects, as well as inducing vasodilation and cardio-protection. However, endogenous levels of melatonin in treatment-naïve patients with PH and their clinical significance are still unknown. Plasma levels of endogenous melatonin were measured by liquid chromatography-tandem mass spectrometry in PH patients ( = 64, 43 pulmonary arterial hypertension (PAH) and 21 chronic thromboembolic PH (CTEPH)) and healthy controls ( = 111). Melatonin levels were higher in PH, PAH, and CTEPH patients when compared with controls (Median 118.7 (IQR 108.2-139.9), 118.9 (109.3-147.7), 118.3 (106.8-130.1) versus 108.0 (102.3-115.2) pM, respectively, all < 0.001). The mortality was 26% (11/43) in the PAH subgroup during a long-term follow-up of 42 (IQR: 32-58) months. Kaplan-Meier analysis showed that, in the PAH subgroup, patients with melatonin levels in the 1st quartile (<109.3 pM) had a worse survival than those in quartile 2-4 (Mean survival times were 46 (95% CI: 30-65) versus 68 (58-77) months, Log-rank, = 0.026) with an increased hazard ratio of 3.5 (95% CI: 1.1-11.6, = 0.038). Endogenous melatonin was increased in treatment-naïve patients with PH, and lower levels of melatonin were associated with worse long-term survival in patient with PAH.
据报道，外源性褪黑素对动物模型中的肺动脉高压（PH）治疗有益。其涉及多种机制，褪黑素具有抗氧化和抗炎作用，还能诱导血管舒张和心脏保护。然而，未经治疗的PH患者体内褪黑素的内源性水平及其临床意义仍不清楚。通过液相色谱 - 串联质谱法测量了PH患者（n = 64，其中43例为肺动脉高压（PAH），21例为慢性血栓栓塞性PH（CTEPH））和健康对照者（n = 111）血浆中内源性褪黑素的水平。与对照组相比，PH、PAH和CTEPH患者的褪黑素水平更高（中位数分别为118.7（四分位间距108.2 - 139.9）、118.9（109.3 - 147.7）、118.3（106.8 - 130.1），而对照组为108.0（102.3 - 115.2）pM，所有p值均<0.001）。在42（四分位间距：32 - 58）个月的长期随访中，PAH亚组的死亡率为26%（11/43）。Kaplan - Meier分析显示，在PAH亚组中，褪黑素水平处于第一四分位数（<109.3 pM）的患者生存率低于处于四分位数2 - 4的患者（平均生存时间分别为46（95%置信区间：30 - 65）个月和68（58 - 77）个月，对数秩检验，p = 0.026），风险比增加3.5（95%置信区间：1.1 - 11.6，p = 0.038）。未经治疗的PH患者内源性褪黑素增加，而PAH患者中较低的褪黑素水平与较差的长期生存率相关。
