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(一种增强神经代谢的神经内分泌肽,作用于下丘脑以抑制食欲)和脂连蛋白(一种具有胰岛素敏感性,抗炎和抗增殖特性的蛋白质)参与了肺动脉高压(PAH)的病理生物学研究。我们假设PAH患者的血浆瘦素和脂联素以及瘦素/脂联素比值异常,并且其水平随随访期间的疾病严重程度和功能变化而变化。我们在16周,国际,多中心,双盲,安慰剂对照的FREEDOM-C2研究中对一组患者进行了检验。在310位随机分组的PAH患者中,有178位在基线和第16周采集了血液。基线血浆瘦素和脂联素浓度分别为25±±31μng/ mL和7.8±±6.1μg/ mL。瘦素,脂联素和瘦素/脂联素在16周时的变化很小。基线时的瘦素与年龄增加,BMI升高,Borg呼吸困难指数升高和NT-pro BNP降低显着相关。即使调整背景治疗和病因,女性的瘦素水平也比男性高(30.5±33.2 vs 7.2±6.4μng/ mL)(线性回归:β≥21.8,P <0.001)。脂联素与BMI负相关,与NT-pro BNP正相关。瘦体重,脂联素和瘦素/脂联素之比的变化(按体重在16周时调整)不能预测功能等级,6分钟步行距离或一,二,三年或四年的生存率。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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