Leptin (a neuroendocrine peptide that enhances metabolism and acts on the hypothalamus to suppress appetite) and adiponectin (a protein that has insulin-sensitizing, anti-inflammatory, and antiproliferative properties) are involved in the pathobiology of pulmonary arterial hypertension (PAH). We hypothesized that plasma leptin and adiponectin as well as the leptin/adiponectin ratio are abnormal in PAH patients and their levels track with disease severity and functional changes during follow-up. We tested this hypothesis in a cohort of patients included in the 16-week, international, multicenter, double-blind, placebo-controlled FREEDOM-C2 study. Blood was collected at baseline and week 16 in 178 out of 310 randomized patients with PAH. Baseline plasma leptin and adiponectin concentrations were 25 ± 31 ng/mL and 7.8 ± 6.1 ug/mL, respectively. Leptin, adiponectin, and leptin/adiponectin (mean ± SD) changes at 16 week were of small magnitude. Leptin at baseline was significantly associated with older age, higher BMI, higher Borg dyspnea index, and lower NT-pro BNP. Women had higher levels of leptin than men (30.5 ± 33.2 versus 7.2 ± 6.4 ng/mL), even when adjusting for background therapy and etiology (linear regression: β = 21.8, P < 0.001). Adiponectin was negatively associated with BMI and positively associated with NT-pro BNP. Changes in leptin, adiponectin, and leptin/adiponectin ratio adjusted for weight at 16 weeks did not predict functional class, distance walk in 6 min or survival at one, two, three, or four years. Plasma leptin and adiponectin at baseline and their change at 16-week do not appear to significantly impact prognosis in PAH.

译文

瘦素 (一种神经内分泌肽,可增强新陈代谢并作用于下丘脑以抑制食欲) 和脂联素 (一种具有胰岛素致敏,抗炎和抗增殖特性的蛋白质) 参与肺动脉高压 (PAH) 的病理生物学。我们假设PAH患者的血浆瘦素和脂联素以及瘦素/脂联素比率异常,并且它们的水平与随访期间的疾病严重程度和功能变化有关。我们在16周,国际,多中心,双盲,安慰剂对照FREEDOM-C2研究的患者队列中测试了这一假设。在310例PAH随机患者中,178例在基线和第16周采集血液。基线血浆瘦素和脂联素浓度分别为25   ±   31  ng/mL和7.8   ±   6.1 ug/mL。16周时瘦素、脂联素、瘦素/脂联素 (mean   ±  SD) 变化幅度较小。基线时瘦素与年龄较大、BMI较高、Borg呼吸困难指数和NT-pro BNP较低显著相关。即使在调整背景治疗和病因 (线性回归: β   =   21.8,p  <  0.001) 的情况下,女性的瘦素水平也高于男性 (30.5   ±   33.2对7.2   ±   6.4  ng/mL)。脂联素与BMI呈负相关,与NT-pro BNP呈正相关。瘦素,脂联素和瘦素/脂联素比在16周时根据体重调整后的变化不能预测功能等级,6  min的步行距离或1、2、3或4年的存活。基线时血浆瘦素和脂联素及其在16周时的变化似乎并未显着影响PAH的预后。

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